1: Int Immunopharmacol. 2007 Apr;7(4):473/82. Epub 2007 Jan 8.
Pure compound from Boswellia serrata extract exhibits anti/inflammatory property
in human PBMCs and mouse macrophages through inhibition of TNFalpha, IL/1beta,
NO and MAP kinases.
Gayathri B, Manjula N, Vinaykumar KS, Lakshmi BS, Balakrishnan A.
Centre for Biotechnology, Anna University, Chennai, India.
The aim of the present study is to probe the anti/inflammatory potential of the
plant Boswellia serrata by studying the effect of the crude extract and the pure
compound isolated from it on key inflammatory mediators like TNFalpha, IL/1beta,
and NO thus enabling the understanding of the key signaling events involved. The
crude methanolic extract and the pure compound were analysed for their
inhibitory effect on TNFalpha, IL/1beta and IL/6. The results demonstrated that
all three cytokines are down regulated when PBMCs are cultured in the presence
of crude extract or the pure compound at various time points. Observations on
Th1/Th2 cytokines revealed marked down regulation of Th1 cytokines IFNgamma and
IL/12 while the Th2 cytokines IL/4 and IL/10 were up regulated upon treatment
with crude extract and pure compound. The extract and the pure compound isolated
also showed considerable inhibition of NO production in activated RAW 264.7
cells, possibly via suppression of inducible NO synthase mRNA expression.
Further to elucidate the underlying mechanism of action the effect of 12/ursene
2/diketone on LPS/induced activation of MAPK has also been examined. Our results
demonstrated that 12/ursene 2/diketone inhibits the expression of
pro/inflammatory cytokines and mediators via inhibition of phosphorylation of
the MAP kinases JNK and p38 while no inhibition was seen in ERK phosphorylation
in LPS/stimulated PBMCs. The above study therefore indicates that the crude
methanolic extract and the isolated pure compound are capable of carrying out a
natural anti/inflammatory activity at sites where chronic inflammation is
present by switching off the pro/inflammatory cytokines and mediators, which
initiate the process.
PMID: 17321470 [PubMed / in process]
2: Phytomedicine. 2007 Feb 7; [Epub ahead of print]
Screening of plant extracts for antimicrobial activity against bacteria and
yeasts with dermatological relevance.
Weckesser S, Engel K, Simon/Haarhaus B, Wittmer A, Pelz K, Schempp CM.
Department of Dermatology, University of Freiburg, Hauptstrasse 7, 79104
Freiburg, Germany.
There is cumulative resistance against antibiotics of many bacteria. Therefore,
the development of new antiseptics and antimicrobial agents for the treatment of
skin infections is of increasing interest. We have screened six plant extracts
and isolated compounds for antimicrobial effects on bacteria and yeasts with
dermatological relevance. The following plant extracts have been tested:
Gentiana lutea, Harpagophytum procumbens, Boswellia serrata (dry extracts),
Usnea barbata, Rosmarinus officinalis and Salvia officinalis (supercritical
carbon dioxide [CO(2)] extracts). Additionally, the following characteristic
plant substances were tested: usnic acid, carnosol, carnosic acid, ursolic acid,
oleanolic acid, harpagoside, boswellic acid and gentiopicroside. The extracts
and compounds were tested against 29 aerobic and anaerobic bacteria and yeasts
in the agar dilution test. U. barbata/extract and usnic acid were the most
active compounds, especially in anaerobic bacteria. Usnea CO(2)/extract
effectively inhibited the growth of several Gram/positive bacteria like
Staphylococcus aureus (including methicillin/resistant strains / MRSA),
Propionibacterium acnes and Corynebacterium species. Growth of the dimorphic
yeast Malassezia furfur was also inhibited by Usnea/extract. Besides the
Usnea/extract, Rosmarinus/, Salvia/, Boswellia/ and Harpagophytum/extracts
proved to be effective against a panel of bacteria. It is concluded that due to
their antimicrobial effects some of the plant extracts may be used for the
topical treatment of skin disorders like acne vulgaris and seborrhoic eczema.
PMID: 17291738 [PubMed / as supplied by publisher]
3: J Chromatogr B Analyt Technol Biomed Life Sci. 2006 Nov 11; [Epub ahead of
print]
Estimation of boswellic acids from market formulations of Boswellia serrata
extract and 11/keto beta/boswellic acid in human plasma by high/performance
thin/layer chromatography.
Shah SA, Rathod IS, Suhagia BN, Patel DA, Parmar VK, Shah BK, Vaishnavi VM.
Department of Quality Assurance, L.M. College of Pharmacy, Ahmedabad 380009,
India.
A rapid and sensitive high/performance thin/layer chromatographic (HPTLC) method
was developed and validated for the quantitative estimation of boswellic acids
in formulation containing Boswellia serrata extract (BSE) and 11/keto
beta/boswellic acid in human plasma. Simple extraction method was used for
isolation of boswellic acid from formulation sample and acidified plasma sample.
The isolated samples were chromatographed on silica gel 60F(254)/TLC plates,
developed using ternary/solvent system (hexane/chloroform/methanol, 5:5:0.5,
v/v) and scanned at 260nm. The linearity range for 11/KBA spiked in 1ml of
plasma was 29.15/145.75ng with average recovery of 91.66%. The limit of
detection and limit of quantification for 11/KBA in human plasma were found to
be 8.75ng/ml and 29.15ng/ml. The developed method was successfully applied for
the assay of market formulations containing BSE and to determine plasma level of
11/keto beta/boswellic acid in a clinical pilot study.
PMID: 17101304 [PubMed / as supplied by publisher]
4: J Sep Sci. 2006 Sep;29(14):2245/50.
Separation and quantification of terpenoids of Boswellia serrata Roxb. extract
by planar chromatography techniques (TLC and AMD).
Pozharitskaya ON, Ivanova SA, Shikov AN, Makarov VG.
Interregional Center "Adaptogen", St. Petersburg, Russia.
An high/performance TLC (HPTLC) method for the separation of boswellic acids,
the active constituents in Boswellia serrata extract, has been developed and TLC
of these compounds on silica by automated multiple development (AMD) using
solvent gradients was performed. Enhancement of the separation of boswellic
acids on HPTLC plates was carried out by AMD chromatography. Densitometric
analysis of the developed plate was carried out to quantify the four boswellic
acids. 11/Keto/beta/boswellic acid (KBA) and acetyl/11/keto/beta/boswellic acid
(AKBA) were quantified by densitometric scanning of the developed plate at 254
nm. beta/Boswellic acid (BA) and acetyl/beta/boswellic acid (ABA) were
quantified after derivatization with anisaldehyde sulfuric acid reagent at 560
nm. The AMD system provided a clean separation according to polarity for each of
the four groups studied and good results were obtained. The proposed HPTLC
method for the simultaneous quantification of the major boswellic acids BA, ABA,
KBA, and AKBA was found to be simple, precise, specific, sensitive, and accurate
and can be used for routine quality control and for the quantification of these
compounds in plant materials. The study of market products revealed significant
variations in the content of these pharmacologically active compounds in
commercial samples.
Publication Types:
Research Support, Non/U.S. Gov't
PMID: 17069256 [PubMed / in process]
5: Cochrane Database Syst Rev. 2006 Oct 18;(4):CD003575.
Update of:
Cochrane Database Syst Rev. 2005;(4):CD003575.
Interventions for treating collagenous colitis.
Chande N, McDonald JW, MacDonald JK.
LHSC//South Street Hospital, Mailbox 55, 375 South Street, London, Ontario,
CANADA. nchande2@uwo.ca
BACKGROUND: Collagenous colitis is a disorder that is recognized as a cause of
chronic diarrhea. Treatment has been based mainly on anecdotal evidence. This
review was performed to identify therapies for collagenous colitis that have
been proven in randomized trials. OBJECTIVES: To determine effective treatments
for patients with clinically active collagenous colitis. SEARCH STRATEGY:
Relevant papers published between 1970 and June 2006 were identified via the
MEDLINE and PUBMED databases. Manual searches from the references of identified
papers, as well as review papers on collagenous or microscopic colitis were
performed to identify additional studies. Abstracts from major
gastroenterological meetings were searched to identify research submitted in
abstract form only. Finally, the Cochrane Controlled Trials Register and the
Cochrane Inflammatory Bowel Disease and Functional Bowel Disorders Group
Specialized Trials Register were searched for other studies. SELECTION CRITERIA:
Seven randomized trials were identified. One trial studied bismuth subsalicylate
(published in abstract form only), one trial studied Boswellia serrata extract
(published in abstract form only), one trial studied probiotics, one trial
studied prednisolone, and 3 trials studied budesonide for the therapy of
collagenous colitis. DATA COLLECTION AND ANALYSIS: Data were extracted
independently by each author onto 2x2 tables (treatment versus placebo and
response versus no response). For therapies assessed in one trial only, p/values
were derived using the chi/square test. For therapies assessed in more than one
trial, summary test statistics were derived using the Peto odds ratio and 95%
confidence intervals. Data were combined for analysis only if the outcomes were
sufficiently similar in definition. MAIN RESULTS: There were 9 patients with
collagenous colitis in the trial studying bismuth subsalicylate (nine 262 mg
tablets daily for 8 weeks). Those randomized to active drug were more likely to
have clinical (p = 0.003) and histological (p = 0.003) improvement than those
assigned to placebo. Eleven patients were enrolled in the trial studying
prednisolone (50 mg daily for 2 weeks). There was a trend towards clinical
response in patients on active medication compared to placebo (p = 0.064). The
effect of prednisolone on histologic improvement was not studied. Thirty/one
patients were enrolled in the Boswellia serrata extract trial. Clinical
improvement was noted in 44% of patients who received active treatment compared
to 27% of patients who received placebo (p = 0.32). Twenty/nine patients were
enrolled in the probiotics trial. Clinical improvement was noted in 29% of
patients who received probiotics compared to 13% of patients who received
placebo (p = 0.635). A total of 94 patients were enrolled in 3 trials studying
budesonide (9 mg daily or in a tapering schedule for 6 to 8 weeks). The pooled
odds ratio for clinical response to treatment with budesonide was 12.32 (95% CI
5.53/27.46), with a number needed to treat of 2 patients. There was significant
histological improvement with treatment in all 3 trials studying budesonide
therapy. Budesonide also appears to improve patients' quality of life. AUTHORS'
CONCLUSIONS: Budesonide is effective for the treatment of collagenous colitis.
The evidence for benefit with bismuth subsalicylate is weaker. The effectiveness
of prednisolone, Boswellia serrata extract, probiotics and other therapies for
induction or maintenance of remission of collagenous colitis is unknown and
requires further study.
Publication Types:
Meta/Analysis
Review
PMID: 17054177 [PubMed / indexed for MEDLINE]
6: J Clin Rheumatol. 2004 Oct;10(5):236/245.
A 32/Week Randomized, Placebo/Controlled Clinical Evaluation of RA/11, an
Ayurvedic Drug, on Osteoarthritis of the Knees.
Chopra A, Lavin P, Patwardhan B, Chitre D.
From the *Center for Rheumatic Diseases, Inlaks and Budhrani Hospital, Bharati
Hospital Medical College (Deemed University), Pune, India; daggerAverion, Inc.,
Framingham, Massachusetts; the double daggerSchool of Health Sciences,
University of Pune, India; and section signBIO/VED Pharmaceuticals, Inc., San
Jose, California.
BACKGROUND:: The ancient Indian (Asian) Ayurvedic medicinal system uses
herbomineral drugs to treat arthritis. Despite centuries of use, very few have
been tested by drug trials. RA/11 (ARTREX, MENDAR), a standardized multiplant
Ayurvedic drug (Withania somnifera, Boswellia serrata, Zingiber officinale, and
Curcuma longa) is currently used to treat arthritis. OBJECTIVE:: The objective
of this study was to evaluate the efficacy and safety of RA/11 in patients with
symptomatic osteoarthritis (OA) of the knees. METHODS:: A total of 358 patients
with chronic knee pain were screened free/of/cost in "arthritis camps" in an
Indian metropolis. Ninety patients with primary OA of the knees (ACR
classification; Arthritis Rheum 1986;29:1039/1049) were found eligible
(postanalgesic washout pain visual analog score [VAS] >/=40 mm in either or both
knees on body weight/bearing activities) to enroll into a randomized,
double/blind, placebo/controlled, parallel efficacy, single/center, 32/week drug
trial (80% power to detect 25% difference, P = 0.05, 2/sided). Concurrent
analgesics/nonsteroidal antiinflammatory drugs and steroids in any form were not
allowed. Lifestyle and/or dietary restrictions, as per routine Ayurveda
practices, were not imposed. Pain VAS (maximum pain in each knee recorded by the
patient during the preceding 48 hours) and modified WOMAC (Western Ontario
McMaster University OA Index, Likert scale, version 3.0) were the primary
efficacy variables. The WOMAC section on "physical function difficulty" was
modified for Indian use and validated before the trial. Routine laboratory
testing was primarily done to monitor drug safety. At baseline, the groups
(active = 45, placebo = 45) were well matched for several measures (mean pain
VAS: active = 6.17; placebo = 6.5). RESULTS:: 1) Efficacy: Compared with
placebo, the mean reduction in pain VAS at week 16 (active = 2.7, placebo = 1.3)
and week 32 (active = 2.8, placebo = 1.8) in the active group was significantly
(P <0.05, analysis of variance [ANOVA]) better. Similarly, the improvement in
the WOMAC scores at week 16 and week 32 were also significantly superior (P
<0.01, ANOVA) in the active group. 2) Safety: Both the groups reported mild
adverse events (AE) without any significant difference. 3) Withdrawals:
Twenty/eight patients were discontinued. None reported drug/related toxicity.
The majority failed follow up/compliance. No differences were observed between
the groups. CONCLUSION:: This controlled drug trial demonstrates the potential
efficacy and safety of RA/ 11 in the symptomatic treatment of OA knees over 32
weeks of therapy.
PMID: 17043520 [PubMed / as supplied by publisher]
7: Planta Med. 2006 Nov;72(14):1285/9. Epub 2006 Oct 4.
Characterization of 3alpha/acetyl/11/keto/alpha/boswellic acid, a pentacyclic
triterpenoid inducing apoptosis in vitro and in vivo.
Buchele B, Zugmaier W, Estrada A, Genze F, Syrovets T, Paetz C, Schneider B,
Simmet T.
Institute of Pharmacology of Natural Products and Clinical Pharmacology,
University of Ulm, Ulm, Germany.
3Alpha/acetyl/11/keto/alpha/boswellic acid
(3alpha/acetoxy/11/oxo/olean/12/en/24/oic acid, 1) was synthesized by a
radical/type reaction using bromine and 3alpha/acetyl/alpha/boswellic acid
isolated from the oleo/gum/resin of Boswellia carterii. 1D and 2D NMR (COSY,
HMBC, ROESY) at 500 MHz were used for shift assignments and structure
verification. The compound investigated is present in a herbal preparation
extracted from Boswellia serrata oleo/gum/resin, it inhibits the growth of
chemotherapy/resistant human PC/3 prostate cancer cells in vitro and induces
apoptosis as shown by activation of caspase 3 and the induction of DNA
fragmentation. In addition, compound 1 is active IN VIVO as shown by inhibition
of proliferation and induction of apoptosis in PC/3 prostate cancer cells
xenotransplanted onto the chick chorioallantoic membrane.
Publication Types:
Research Support, Non/U.S. Gov't
PMID: 17022003 [PubMed / indexed for MEDLINE]
8: J Neurooncol. 2007 Mar;82(1):91/3. Epub 2006 Sep 26.
A lipoxygenase inhibitor in breast cancer brain metastases.
Flavin DF.
Foundation for Collaborative Medicine and Research, 24 Midwood Drive, Greenwich,
CT, 06831, USA, Dana_FK@hotmail.com.
The complication of multiple brain metastases in breast cancer patients is a
life threatening condition with limited success following standard therapies.
The arachidonate lipoxygenase pathway appears to play a role in brain tumor
growth as well as inhibition of apoptosis in in/vitro studies. The down
regulation of these arachidonate lipoxygenase growth stimulating products
therefore appeared to be a worthwile consideration for testing in brain
metastases not responding to standard therapy. Boswellia serrata, a lipoxygenase
inhibitor was applied for this inhibition. Multiple brain metastases were
successfully reversed using this method in a breast cancer patient who had not
shown improvement after standard therapy. The results suggest a potential new
area of therapy for breast cancer patients with brain metastases that may be
useful as an adjuvant to our standard therapy.
PMID: 17001517 [PubMed / in process]
9: Planta Med. 2006 May;72(6):507/13.
Modulation of Pgp function by boswellic acids.
Weber CC, Reising K, Muller WE, Schubert/Zsilavecz M, Abdel/Tawab M.
Institute of Pharmacology, ZAFES, Biocenter, University of Frankfurt, Germany.
Boswellic acids, the main active ingredients of Boswellia serrata, are gaining
more and more importance in the treatment of peritumoural oedema and chronic
inflammatory diseases. They may be even considered as alternative drugs to
corticosteroids in reducing cerebral peritumoural oedema. An important focus for
drugs acting in the central nervous system is achieving a high extent of brain
penetration. Today there is increasing evidence for the importance of
transporters, especially P/glycoprotein (Pgp), for drug disposition and
resulting clinical response. Pharmacokinetic studies revealed that the
concentrations of the potent keto derivatives, the 11/keto/beta/boswellic acid
(KBA) and the acetyl/11/keto/beta/boswellic acid (AKBA), in proportion to
boswellic acids lacking a keto group, like the beta/boswellic acid, are much
lower in plasma than in the orally administered extract. Moreover the
brain/plasma ratio for KBA and AKBA determined in preliminary experiments on
rats was only about 0.51 and 0.81, respectively, in spite of their
lipophilicity. Until now little is known about the cerebral pharmacokinetics of
boswellic acids and how it may be influenced. Since many drugs are known to
interact with Pgp at the level of the intestine and the blood/brain barrier the
modulatory potencies of the Boswellia serrata extract of H15(R) and the major
boswellic acids on the transport activity of Pgp have been determined in two in
vitro assays. A human lymphocytic leukaemia cell line (VLB cells) expressing Pgp
was chosen as model for human Pgp, and porcine brain capillary endothelial cells
(PBCEC cells) were taken as model for the blood/brain barrier using calcein
acetoxymethyl ester (calcein/AM) as Pgp substrate. It was found that the
Boswellia extract, as well as the keto/boswellic acids inhibit the transport
activity of Pgp in the micromolecular range in both cell types. No modulation
was observed using those boswellic acids which have no keto group in their
structure. The inhibition of Pgp at the blood/brain barrier by Boswellia extract
is probably not relevant for the brain availability of other Pgp substrates,
because of the low plasma levels determined for KBA and AKBA. However the
presented data could not exclude the possibility of drug interactions caused by
modulation of Pgp by extracts of Boswellia serrata on the gastrointestinal
level.
PMID: 16773534 [PubMed / indexed for MEDLINE]
10: Pak J Pharm Sci. 2006 Apr;19(2):129/33.
Effect of hexane extract of Boswellia serrata oleo/gum resin on chemically
induced liver damage.
Y J, Kamath JV, Asad M.
Krupanidhi College of Pharmacy, 5, Sarjapur Road, Koramangala, Bangalore/560
034, India.
The hexane extract of oleo/gum/resin of Boswellia serrata (BSHE) was evaluated
for its effect on liver injury induced by carbon tetrachloride, paracetamol or
thioacetamide. The BSHE was given in two different doses (87.5 mg/kg p.o. and
175 mg/kg p.o.). Silymarin, a known hepatoprotective agent was used as standard.
The lower dose of BSHE (87.5 mg/kg p.o.) significantly reduced the elevated
levels of serum marker enzymes and prevented the increase in liver weight in all
three models of liver injury, while the higher dose showed mild hepatoprotective
activity. The hepatoprotective effect of lower dose of BSHE was supported by
changes in histopathology. It was concluded that hexane extract of
oleo/gum/resin of Boswellia serrata plant in lower doses possess
hepatoprotective activity.
Publication Types:
Comparative Study
PMID: 16751123 [PubMed / in process]
11: BMC Complement Altern Med. 2006 May 22;6:19.
Use of complementary and alternative medicine in Germany / a survey of patients
with inflammatory bowel disease.
Joos S, Rosemann T, Szecsenyi J, Hahn EG, Willich SN, Brinkhaus B.
Department of General Practice and Health Services Research, University of
Heidelberg, Germany. stefanie.joos@med.uni/heidelberg.de
BACKGROUND: Previous studies have suggested an increasing use of complementary
and alternative medicine (CAM) in patients with inflammatory bowel disease
(IBD). The aim of our study was to evaluate the use of CAM in German patients
with IBD. METHODS: A questionnaire was offered to IBD patients participating in
patient workshops which were organized by a self/help association, the German
Crohn's and Colitis Association. The self/administered questionnaire included
demographic and disease/related data as well as items analysing the extent of
CAM use and satisfaction with CAM treatment. Seven commonly used CAM methods
were predetermined on the questionnaire. RESULTS: 413 questionnaires were
completed and included in the analysis (n = 153 male, n = 260 female; n = 246
Crohn's disease, n = 164 ulcerative colitis). 52 % of the patients reported CAM
use in the present or past. In detail, homeopathy (55%), probiotics (43%),
classical naturopathy (38%), Boswellia serrata extracts (36%) and
acupuncture/Traditional Chinese Medicine (TCM) (33%) were the most frequently
used CAM methods. Patients using probiotics, acupuncture and Boswellia serrata
extracts (incense) reported more positive therapeutic effects than others.
Within the statistical analysis no significant predictors for CAM use were
found. 77% of the patients felt insufficiently informed about CAM. CONCLUSION:
The use of CAM in IBD patients is very common in Germany, although a large
proportion of patients felt that information about CAM is not sufficient.
However, to provide an evidence/based approach more research in this field is
desperately needed. Therefore, physicians should increasingly inform IBD
patients about benefits and limitations of CAM treatment.
PMID: 16716218 [PubMed / indexed for MEDLINE]
12: Aliment Pharmacol Ther. 2006 Jun 1;23(11):1525/34.
Comment in:
Aliment Pharmacol Ther. 2006 Aug 1;24(3):561; author reply 562.
Systematic review: microscopic colitis.
Nyhlin N, Bohr J, Eriksson S, Tysk C.
Department of Medicine, Division of Gastroenterology, Orebro University
Hospital, Orebro, Sweden.
BACKGROUND: Collagenous and lymphocytic colitis are fairly common causes of
chronic non/bloody diarrhoea, especially in elderly female. AIM: To present a
systematic review of microscopic colitis. METHODS: A PubMed search using the
MeSH terms microscopic colitis, collagenous colitis, lymphocytic colitis and
chronic diarrhoea was performed. RESULTS: Annual incidence of each disorder is
4/6/100,000 inhabitants. The aetiology is unknown. Clinical characteristics are
well described and there is an association with autoimmune diseases. Budesonide
is the best/documented short/term treatment of collagenous colitis. In
meta/analysis pooled odds ratio for clinical response after 6/8 weeks of
treatment was 12.3 (95% CI: 5.5/27.5) in comparison with placebo. The evidence
for bismuth subsalicylate is weaker and the effectiveness of other alternatives
such as loperamide, cholestyramine, aminosalicylates, probiotics, or Boswellia
serrata extract is unknown. Although unproven, in unresponsive severe disease
azathioprine or methotrexate may be tried. No controlled trials have been
carried out in lymphocytic colitis. The long/term prognosis of microscopic
colitis is good, serious complications are rare and there is no increased
mortality. CONCLUSIONS: Clinical and epidemiological aspects of microscopic
colitis are well described. Budesonide is the best/documented short/term therapy
in collagenous colitis, but the optimal long/term strategy needs further study.
Controlled treatment data of lymphocytic colitis are awaited for.
Publication Types:
Research Support, Non/U.S. Gov't
Review
PMID: 16696800 [PubMed / indexed for MEDLINE]
13: Asia Pac J Clin Nutr. 2006;15(2):143/52.
Natural products and anti/inflammatory activity.
Yuan G, Wahlqvist ML, He G, Yang M, Li D.
Department of Food Science and Nutrition, Zhejiang University, 268 Kaixuan Road,
Hangzhou, Zhejiang, China 310029.
The aim of this review paper was to summarise some commonly available natural
products and their anti/inflammatory activity. We have collected data from
MEDLINE, Current Contents and scientific journals, which included 92
publications. There are numerous natural products detailed in this literature;
however we have summarized a few of the most commonly available and potent ones.
In this paper, the natural products with anti/inflammatory activity including
curcumin, parthenolide, cucurbitacins, 1,8/cineole, pseudopterosins, lyprinol,
bromelain, flavonoids, saponins, marine sponge natural products and Boswellia
serrata gum resin were reviewed. Natural products play a significant role in
human health in relation to the prevention and treatment of inflammatory
conditions. Further studies are being conducted to investigate the mechanism of
action, metabolism, safety and long term side effect of these natural products,
as well as interactions between these natural products with food and drug
components.
Publication Types:
Review
PMID: 16672197 [PubMed / indexed for MEDLINE]
14: Planta Med. 2006 Apr 24; [Epub ahead of print]
Modulation of Pgp Function by Boswellic Acids.
Weber CC, Reising K, Muller WE, Schubert/Zsilavecz M, Abdel/Tawab M.
Institute of Pharmacology, ZAFES, Biocenter, University of Frankfurt, Germany.
Boswellic acids, the main active ingredients of BOSWELLIA SERRATA, are gaining
more and more importance in the treatment of peritumoural oedema and chronic
inflammatory diseases. They may be even considered as alternative drugs to
corticosteroids in reducing cerebral peritumoural oedema. An important focus for
drugs acting in the central nervous system is achieving a high extent of brain
penetration. Today there is increasing evidence for the importance of
transporters, especially P/glycoprotein (Pgp), for drug disposition and
resulting clinical response. Pharmacokinetic studies revealed that the
concentrations of the potent keto derivatives, the 11/keto/beta/boswellic acid
(KBA) and the acetyl/11/keto/beta/boswellic acid (AKBA), in proportion to
boswellic acids lacking a keto group, like the beta/boswellic acid, are much
lower in plasma than in the orally administered extract. Moreover the
brain/plasma ratio for KBA and AKBA determined in preliminary experiments on
rats was only about 0.51 and 0.81, respectively, in spite of their
lipophilicity. Until now little is known about the cerebral pharmacokinetics of
boswellic acids and how it may be influenced. Since many drugs are known to
interact with Pgp at the level of the intestine and the blood/brain barrier the
modulatory potencies of the BOSWELLIA SERRATA extract of H15(R) and the major
boswellic acids on the transport activity of Pgp have been determined in two IN
VITRO assays. A human lymphocytic leukaemia cell line (VLB cells) expressing Pgp
was chosen as model for human Pgp, and porcine brain capillary endothelial cells
(PBCEC cells) were taken as model for the blood/brain barrier using calcein
acetoxymethyl ester (calcein/AM) as Pgp substrate. It was found that the
BOSWELLIA extract, as well as the keto/boswellic acids inhibit the transport
activity of Pgp in the micromolecular range in both cell types. No modulation
was observed using those boswellic acids which have no keto group in their
structure. The inhibition of Pgp at the blood/brain barrier by BOSWELLIA extract
is probably not relevant for the brain availability of other Pgp substrates,
because of the low plasma levels determined for KBA and AKBA. However the
presented data could not exclude the possibility of drug interactions caused by
modulation of Pgp by extracts of BOSWELLIA SERRATA on the gastrointestinal
level.
PMID: 16636962 [PubMed / as supplied by publisher]
15: Br J Pharmacol. 2006 Jun;148(4):553/60. Epub 2006 Apr 24.
Effect of Boswellia serrata on intestinal motility in rodents: inhibition of
diarrhoea without constipation.
Borrelli F, Capasso F, Capasso R, Ascione V, Aviello G, Longo R, Izzo AA.
Department of Experimental Pharmacology, University of Naples Federico II,
Italy.
Clinical studies suggest that the Ayurvedic plant Boswellia serrata may be
effective in reducing diarrhoea in patients with inflammatory bowel disease. In
the present study, we evaluated the effect of a Boswellia serrata gum resin
extract (BSE) on intestinal motility and diarrhoea in rodents. BSE depressed
electrically/, acetylcholine/, and barium chloride/induced contractions in the
isolated guinea/pig ileum, being more potent in inhibiting the contractions
induced by acetylcholine and barium chloride. The inhibitory effect of BSE on
acetylcholine/induced contractions was reduced by the L/type Ca(2+) channel
blockers verapamil and nifedipine, but not by the sarcoplasmic reticulum
Ca(2+)/ATPase inhibitor cyclopiazonic acid, by the phosphodiesterase type IV
inhibitor rolipram or by the lipoxygenase inhibitor zileuton.
3/acetyl/11/keto/beta/boswellic acid, one of the main active ingredients of B.
serrata, inhibited acetylcholine/induced contractions. BSE inhibited upper
gastrointestinal transit in croton oil/treated mice as well as castor
oil/induced diarrhoea. However, BSE did not affect intestinal motility in
control mice, both in the small and in the large intestine. It is concluded that
BSE directly inhibits intestinal motility with a mechanism involving L/type
Ca(2+) channels. BSE prevents diarrhoea and normalizes intestinal motility in
pathophysiological states without slowing the rate of transit in control
animals. These results could explain, at least in part, the clinical efficacy of
this Ayurvedic remedy in reducing diarrhoea in patients with inflammatory bowel
disease.
PMID: 16633355 [PubMed / indexed for MEDLINE]
16: J Immunol. 2006 Mar 1;176(5):3127/40.
Acetyl/11/keto/beta/boswellic acid potentiates apoptosis, inhibits invasion, and
abolishes osteoclastogenesis by suppressing NF/kappa B and NF/kappa B/regulated
gene expression.
Takada Y, Ichikawa H, Badmaev V, Aggarwal BB.
Cytokine Research Section, Department of Experimental Therapeutics, University
of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
Acetyl/11/keto/beta/boswellic acid (AKBA), a component of an Ayurvedic
therapeutic plant Boswellia serrata, is a pentacyclic terpenoid active against a
large number of inflammatory diseases, including cancer, arthritis, chronic
colitis, ulcerative colitis, Crohn's disease, and bronchial asthma, but the
mechanism is poorly understood. We found that AKBA potentiated the apoptosis
induced by TNF and chemotherapeutic agents, suppressed TNF/induced invasion, and
inhibited receptor activator of NF/kappaB ligand/induced osteoclastogenesis, all
of which are known to require NF/kappaB activation. These observations
corresponded with the down/regulation of the expression of NF/kappaB/regulated
antiapoptotic, proliferative, and angiogenic gene products. As examined by DNA
binding, AKBA suppressed both inducible and constitutive NF/kappaB activation in
tumor cells. It also abrogated NF/kappaB activation induced by TNF, IL/1beta,
okadaic acid, doxorubicin, LPS, H2O2, PMA, and cigarette smoke. AKBA did not
directly affect the binding of NF/kappaB to the DNA but inhibited sequentially
the TNF/induced activation of IkappaBalpha kinase (IKK), IkappaBalpha
phosphorylation, IkappaBalpha ubiquitination, IkappaBalpha degradation, p65
phosphorylation, and p65 nuclear translocation. AKBA also did not directly
modulate IKK activity but suppressed the activation of IKK through inhibition of
Akt. Furthermore, AKBA inhibited the NF/kappaB/dependent reporter gene
expression activated by TNFR type 1, TNFR/associated death domain protein,
TNFR/associated factor 2, NF/kappaB/inducing kinase, and IKK, but not that
activated by the p65 subunit of NF/kappaB. Overall, our results indicated that
AKBA enhances apoptosis induced by cytokines and chemotherapeutic agents,
inhibits invasion, and suppresses osteoclastogenesis through inhibition of
NF/kappaB/regulated gene expression.
Publication Types:
Research Support, N.I.H., Extramural
Research Support, Non/U.S. Gov't
Research Support, U.S. Gov't, Non/P.H.S.
PMID: 16493072 [PubMed / indexed for MEDLINE]
17: Am J Physiol Gastrointest Liver Physiol. 2006 Jun;290(6):G1131/7. Epub 2006
Jan 19.
Mechanisms underlying the anti/inflammatory actions of boswellic acid
derivatives in experimental colitis.
Anthoni C, Laukoetter MG, Rijcken E, Vowinkel T, Mennigen R, Muller S, Senninger
N, Russell J, Jauch J, Bergmann J, Granger DN, Krieglstein CF.
Department of Molecular and Cellular Physiology, Louisiana State University
Health Sciences Center, Shreveport, 71130, USA.
Recent clinical trials of the gum resin of Boswellia serrata have shown
promising results in patients with ulcerative colitis. The objective of this
study was to determine whether a semisynthetic form of
acetyl/11/keto/beta/boswellic acid (sAKBA), the most potent anti/inflammatory
component of the resin, also confers protection in experimental murine colitis
induced by dextran sodium sulfate (DSS) to compare its effects with those
standard medications of ulcerative colitis like steroids and to examine whether
leukocyte/endothelial cell adhesion is a major target of action of sAKBA.
Clinical measurements of disease activity and histology were used to assess
disease progression, and intravital microscopy was employed to monitor the
adhesion of leukocytes and platelets in postcapillary venules of the inflamed
colon. sAKBA treatment significantly blunted disease activity as assessed both
grossly and by histology. Similarly, the recruitment of adherent leukocytes and
platelets into inflamed colonic venules was profoundly reduced in mice treated
with sAKBA. Because previous studies in the DSS model have shown that P/selectin
mediates these blood cell/endothelial cell interactions, the expression of
P/selectin in the colonic microcirculation was monitored using the
dual/radiolabeled antibody technique. The treatment of established colitis with
sAKBA largely prevented the P/selectin upregulation normally associated with DSS
colitis. All of the protective responses observed with sAKBA were comparable to
that realized in mice treated with a corticosteroid. Our findings demonstrated
an anti/inflammatory effect of sAKBA and indicated that P/selectin/mediated
recruitment of inflammatory cells is a major site of action for this novel
anti/inflammatory agent.
Publication Types:
Research Support, N.I.H., Extramural
PMID: 16423918 [PubMed / indexed for MEDLINE]
18: Aliment Pharmacol Ther. 2006 Feb 1;23(3):341/9.
Review article: complementary and alternative therapies for inflammatory bowel
disease.
Langmead L, Rampton DS.
Department of Gastroenterology, University College London Hospitals, NHS
Foundation Trust, London, UK. louise.langmead@uclh.nhs.uk
Complementary and alternative medicine includes a wide range of practices and
therapies outside the realms of conventional western medicine. Despite a lack of
scientific data in the form of controlled trials for either efficacy or safety
of complementary and alternative medicine, use by patients with inflammatory
bowel disease, particularly of herbal therapies, is widespread and increasing.
There is limited controlled evidence indicating efficacy of traditional Chinese
medicines, aloe vera gel, wheat grass juice, Boswellia serrata and bovine
colostrum enemas in ulcerative colitis. Encouraging results have also been
reported in small studies of acupuncture for Crohn's disease and ulcerative
colitis. Contrary to popular belief, natural therapies are not necessarily safe:
fatal hepatic and irreversible renal failure have occurred with some
preparations and interactions with conventional drugs are potentially dangerous.
There is a need for further controlled clinical trials of the potential efficacy
of complementary and alternative approaches in inflammatory bowel disease,
together with enhanced legislation to maximize their quality and safety.
Publication Types:
Research Support, Non/U.S. Gov't
Review
PMID: 16422993 [PubMed / indexed for MEDLINE]
19: J Chromatogr A. 2006 Apr 21;1112(1/2):255/62. Epub 2005 Dec 20.
Analysis of frankincense from various Boswellia species with inhibitory activity
on human drug metabolising cytochrome P450 enzymes using liquid chromatography
mass spectrometry after automated on/line extraction.
Frank A, Unger M.
Institute of Pharmacy and Food Chemistry, Julius Maximilians/University
Wurzburg, 97074 Wurzburg, Germany.
In our search for herbal remedies with inhibitory activity on cytochrome P450
(CYP) enzymes, we identified extracts of the gum/resin of Boswellia carteri,
Boswellia frereana, Boswellia sacra and Boswellia serrata as equally potent,
non/selective inhibitors of the major drug metabolising CYP enzymes
1A2/2C8/2C9/2C19/2D6 and 3A4. LC/LC/ESI/MS fingerprint analyses of the boswellic
acids 11/keto/beta/boswellic acid, alpha/boswellic acid, beta/boswellic acid and
their 3/O/acylated derivatives were used for the authentication of the
commercially obtained frankincense samples. Although the boswellic acids could
be identified as moderate to potent inhibitors of the applied CYP enzymes, they
are not the major CYP inhibitory principle of frankincense.
Publication Types:
Research Support, Non/U.S. Gov't
PMID: 16364338 [PubMed / indexed for MEDLINE]
20: Cochrane Database Syst Rev. 2005 Oct 19;(4):CD003575.
Update in:
Cochrane Database Syst Rev. 2006;(4):CD003575.
Update of:
Cochrane Database Syst Rev. 2004;(1):CD003575.
Interventions for treating collagenous colitis.
Chande N, McDonald JW, Macdonald JK.
BACKGROUND: Collagenous colitis is a disorder that is recognized as a cause of
chronic diarrhea. Treatment has been based mainly on anecdotal evidence. This
review was performed to identify therapies for collagenous colitis that have
been proven in randomized trials. OBJECTIVES: To determine effective treatments
for patients with clinically active collagenous colitis. SEARCH STRATEGY:
Relevant papers published between 1970 and June 2005 were identified via the
MEDLINE and PUBMED databases. Manual searches from the references of identified
papers, as well as review papers on collagenous or microscopic colitis were
performed to identify additional studies. Abstracts from major
gastroenterological meetings were searched to identify research submitted in
abstract form only. Finally, the Cochrane Controlled Trials Register and the
Cochrane Inflammatory Bowel Disease and Functional Bowel Disorders Group
Specialized Trials Register were searched for other studies. SELECTION CRITERIA:
Six randomized trials were identified. One trial studied bismuth subsalicylate
(published in abstract form only), one trial studied Boswellia serrata extract
(published in abstract form only), one trial studied prednisolone, and 3 trials
studied budesonide in the therapy of collagenous colitis. DATA COLLECTION AND
ANALYSIS: Data were extracted independently by each author onto 2x2 tables
(treatment versus placebo and response versus no response). For therapies
assessed in one trial only, p/values were derived using the chi/square test. For
therapies assessed in more than one trial, summary test statistics were derived
using the Peto odds ratio and 95% confidence intervals. Data were combined for
analysis only if the outcomes were sufficiently similar in definition. MAIN
RESULTS: There were 9 patients with collagenous colitis in the trial studying
bismuth subsalicylate (nine 262 mg tablets daily for 8 weeks). Those randomized
to active drug were more likely to have clinical (p = 0.003) and histological (p
= 0.003) improvement than those assigned to placebo. Eleven patients were
enrolled in the trial studying prednisolone (50 mg daily for 2 weeks). There was
a trend towards clinical response in patients on active medication compared to
placebo (p = 0.064). The effect of prednisolone on histologic improvement was
not studied. Thirty/one patients were enrolled in the Boswellia serrata extract
trial. Clinical improvement was noted in 44% of patients who received active
treatment compared to 27% of patients who received placebo (p = 0.32). A total
of 94 patients were enrolled in 3 trials studying budesonide (9 mg daily or in a
tapering schedule for 6 to 8 weeks). The pooled odds ratio for clinical response
to treatment with budesonide was 12.32 (95% CI 5.53 / 27.46), with a number
needed to treat of 2 patients. There was significant histological improvement
with treatment in all 3 trials studying budesonide therapy. Budesonide also
appears to improve patients' quality of life. AUTHORS' CONCLUSIONS: Budesonide
is effective for the treatment of collagenous colitis. The evidence for benefit
with bismuth subsalicylate is weaker. The effectiveness of prednisolone and
Boswellia serrata extract and other therapies for induction or maintenance of
remission of collagenous colitis is unknown and requires further study.
Publication Types:
Meta/Analysis
Review
PMID: 16235328 [PubMed / indexed for MEDLINE]
21: Anal Chem. 2005 Oct 15;77(20):6640/5.
Determination of boswellic acids in brain and plasma by high/performance liquid
chromatography/tandem mass spectrometry.
Reising K, Meins J, Bastian B, Eckert G, Mueller WE, Schubert/Zsilavecz M,
Abdel/Tawab M.
Central Laboratory of German Pharmacists, Carl/Mannich Strasse 20, D/65760
Eschborn, Germany.
Peritumoral edema, one of the major causes for neurological disorders in brain
tumor patients, is mainly treated with steroids, which unfortunately have
significant side effects and interfere with the efficacy of chemotherapy.
Boswellic acids, the main active ingredients of Boswellia serrata, are
antiinflammatory agents, inhibiting 5/lipoxygenase, the key enzyme of
leukotriene biosynthesis and one of the pathophysiological mechanisms of
peritumoral edema. Based on positive results in clinical trials and animal
studies, B. serrata resin dry extract was designated an orphan drug by the
European Commission for the treatment of peritumoral edema resulting from brain
tumors. Thus boswellic acids may be alternative drugs to corticosteroids.
However, the question of the availability of boswellic acids in brain has not
been addressed until now. Accordingly, a highly sensitive LC/MS method has been
developed for the simultaneous determination of KBA and AKBA, the most potent
boswellic acids, in plasma and brain. This method involves matrix/assisted
liquid/liquid extraction on Extrelut NT followed by separation on reversed/phase
high/performance liquid chromatography and tandem mass spectrometry detection
using atmospheric pressure chemical ionization. Excellent linearity was obtained
for the entire calibration range from 5 to 1500 ng/mL KBA and AKBA in plasma and
5 to 1000 ng/mL KBA and AKBA in brain. Validation assays of the lower limit of
quantification as well as for the intra/ and interday precision and accuracy met
the international acceptance criteria for bioanalytical method validation.
Moreover, the interchangeability of calibration curves generated in pork and rat
brain homogenates could be demonstrated. Using the developed analytical method,
KBA and AKBA could be detected for the first time in brain up to a concentration
of 99 and 95 ng/g of brain, respectively, 3 h after the single oral
administration of 240 mg/kg of dry B. serrata resin extract to Wistar rats. The
developed method represents an appropriate tool to further study the
time/dependent distribution of KBA and AKBA in plasma and brain as well as the
absolute brain concentration after multiple doses and contributes thus to the
optimization of the dosage regimen and to a better understanding of the
therapeutic effects of B. serrata.
PMID: 16223251 [PubMed / indexed for MEDLINE]
22: Indian J Exp Biol. 2005 Jun;43(6):509/16.
Extract of gum resins of Boswellia serrata L. inhibits lipopolysaccharide
induced nitric oxide production in rat macrophages along with hypolipidemic
property.
Pandey RS, Singh BK, Tripathi YB.
Department of Medicinal Chemistry, Institute of Medical Sciences, Banaras Hindu
University, Varanasi 221005, India.
Boswellia serrata, Linn F (Burseraceae) is commonly used in Indian system of
medicine (Ayurvedic) as an anti/inflammatory, analgesic, anti/arthritic and
anti/proliferative agent. This study was planned to investigate the
water/soluble fraction of the oleoresin gum of Boswellia serrata (BS extract) on
lipopolysaccharide (LPS) induced nitric oxide (NO) production by macrophages
under in vivo and in vitro conditions. In the previous condition, rats were fed
on atherogenic diet (2.5% cholesterol, 1% cholic acid, 15.7 % saturated fat)
along with the BS extract for 90 days. Blood was collected for lipid profile and
toxicological safety parameters. Peritoneal macrophages were isolated and
cultured to see the LPS induced NO production. Under in vivo experiment, BS
extract significantly reduced serum total cholesterol (38/48 %), increased serum
high/density lipoprotein/ cholesterol (HDL/cholesterol, 22/30%). Under in vitro
experiments with thioglycolate activated macrophages, it inhibited LPS induced
(NO) production with IC 50 value at 662 ng /ml. Further, this fraction, in the
dose of 15 mg/100 g body wt for 90 days, did not show any increase in serum
glutamate/pyruvate transaminase (SGPT) and blood urea, in normal control
animals. However, it significantly reversed the raised SGPT and blood urea in
the atherogenic diet/fed animals. Transverse section of liver and kidney also
supported its protective effect. Thus it may be concluded that water extract of
Boswellia serrata possesses strong hypocholesterolemic property along with
increase in serum HDL. It inhibits the LPS induced NO production by the
activated rat peritoneal macrophages and show hepato/protective and
reno/protective property.
Publication Types:
Research Support, Non/U.S. Gov't
PMID: 15991575 [PubMed / indexed for MEDLINE]
23: Phytochemistry. 2005 Jun;66(12):1499/514.
A chemical investigation by headspace SPME and GC/MS of volatile and
semi/volatile terpenes in various olibanum samples.
Hamm S, Bleton J, Connan J, Tchapla A.
Groupe de Chimie Analytique de Paris Sud (LETIAM) EA 3343, Institut
Universitaire de Technologie d'Orsay, Plateau de Moulon, F/91400 Orsay, France.
sandrhamm@aol.com
Six different olibanum samples with certified botanical origin were analyzed by
headspace SPME/GC/MS in order to define their mono/, sesqui/ and diterpenic
composition, as pertinent criteria of identification. Boswellia carteri and
Boswellia sacra olibanum have quite similar chemical composition, with
isoincensole acetate as the main diterpenic biomarker. Although Boswellia
serrata olibanum also exhibits this biomarker, the presence of methylchavicol,
methyleugenol and an unidentified oxygenated sesquiterpene distinguishes B.
serrata olibanum from the two other species. The characteristic chemical
compounds of Boswellia papyrifera are the diterpenic biomarkers incensole and
its oxide and acetate derivatives, n/octanol and n/octyl acetate. Boswellia
frereana olibanum is devoid of diterpenes of the incensole family but contains a
high amount of many dimers of alpha/phellandrene. The chemical composition of
olibanum, which is demonstrated to be different for each Boswellia species
allowed the determination of the taxonomic origin of frankincense samples
purchased on various markets in East Africa, in the Near East and in Yemen.
Moreover, terpenic fingerprints allowed the botanical origin of olibanum used in
traditional incense mixtures to be identified. Furthermore, this study gave us
the opportunity to assign a botanical origin to an archaeological frankincense
sample.
PMID: 15922374 [PubMed / indexed for MEDLINE]
24: Clin Diagn Lab Immunol. 2005 May;12(5):575/80.
Boswellia carterii extract inhibits TH1 cytokines and promotes TH2 cytokines in
vitro.
Chevrier MR, Ryan AE, Lee DY, Zhongze M, Wu/Yan Z, Via CS.
Research Service, Baltimore VAMHCS and Division of Rheumatology and Clinical
Immunology, University of Maryland School of Medicine, Baltimore, Maryland
21201, USA.
Traditional herbal formulas used to treat inflammatory arthritis in China and
India include Boswellia carterii or Boswellia serrata. They both contain
boswellic acids (BAs) which have been shown to exhibit anti/inflammatory and
antiarthritic properties. This study tests the hypothesis that mixtures of BAs
derived from B. carterii have immunomodulatory properties. B. carterii plant
resin obtained from China was prepared as an ethanol extract, and the presence
of seven BAs was confirmed by column chromatography, high/performance liquid
chromatography, and UV laser desorption/ionization tandem mass spectroscopy. The
extract was then tested for its ability to alter in vitro production of TH1
cytokines (interleukin/2 [IL/2] and gamma interferon) and TH2 cytokines (IL/4
and IL/10) by murine splenocytes. Delivery of the resin extract using ethanol as
a solvent resulted in significant cellular toxicity not seen with the addition
of ethanol alone. By contrast, delivery of the resin extract using a sesame oil
solvent resulted in a dose/dependent inhibition of TH1 cytokines coupled with a
dose/dependent potentiation of TH2 cytokines. These results indicate that a
purified mixture of BAs from B. carterii plant resin exhibits carrier/dependent
immunomodulatory properties in vitro.
Publication Types:
Research Support, N.I.H., Extramural
Research Support, Non/U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
PMID: 15879017 [PubMed / indexed for MEDLINE]
25: DNA Cell Biol. 2005 Apr;24(4):244/55.
Human genome screen to identify the genetic basis of the anti/inflammatory
effects of Boswellia in microvascular endothelial cells.
Roy S, Khanna S, Shah H, Rink C, Phillips C, Preuss H, Subbaraju GV, Trimurtulu
G, Krishnaraju AV, Bagchi M, Bagchi D, Sen CK.
Laboratory of Molecular Medicine, Department of Surgery, The Ohio State
University Medical Center, Columbus, Ohio 43210, USA.
Inflammatory disorders represent a substantial health problem. Medicinal plants
belonging to the Burseraceae family, including Boswellia, are especially known
for their anti/inflammatory properties. The gum resin of Boswellia serrata
contains boswellic acids, which inhibit leukotriene biosynthesis. A series of
chronic inflammatory diseases are perpetuated by leukotrienes. Although
Boswellia extract has proven to be anti/inflammatory in clinical trials, the
underlying mechanisms remain to be characterized. TNF alpha represents one of
the most widely recognized mediators of inflammation. One mechanism by which
TNFalpha causes inflammation is by potently inducing the expression of adhesion
molecules such as VCAM/1. We sought to test the genetic basis of the
antiinflammatory effects of BE (standardized Boswellia extract, 5/Loxin) in a
system of TNF alpha/induced gene expression in human microvascular endothelial
cells. We conducted the first whole genome screen for TNF alpha/ inducible genes
in human microvascular cells (HMEC). Acutely, TNF alpha induced 522 genes and
downregulated 141 genes in nine out of nine pairwise comparisons. Of the 522
genes induced by TNF alpha in HMEC, 113 genes were clearly sensitive to BE
treatment. Such genes directly related to inflammation, cell adhesion, and
proteolysis. The robust BE/sensitive candidate genes were then subjected to
further processing for the identification of BE/sensitive signaling pathways.
The use of resources such as GenMAPP, KEGG, and gene ontology led to the
recognition of the primary BE/sensitive TNF alpha/inducible pathways. BE
prevented the TNF alpha/induced expression of matrix metalloproteinases. BE also
prevented the inducible expression of mediators of apoptosis. Most strikingly,
however, TNF alpha/inducible expression of VCAM/1 and ICAM/1 were observed to be
sensitive to BE. Realtime PCR studies showed that while TNF alpha potently
induced VCAM/1 gene expression, BE completely prevented it. This result
confirmed our microarray findings and built a compelling case for the
anti/inflammatory property of BE. In an in vivo model of carrageenan/induced rat
paw inflammation, we observed a significant antiinflammatory property of BE
consistent with our in vitro findings. These findings warrant further research
aimed at identifying the signaling mechanisms by which BE exerts its
anti/inflammatory effects.
Publication Types:
Comparative Study
PMID: 15812241 [PubMed / indexed for MEDLINE]
26: Planta Med. 2004 Dec;70(12):1155/60.
Effect of food intake on the bioavailability of boswellic acids from a herbal
preparation in healthy volunteers.
Sterk V, Buchele B, Simmet T.
Department of Pharmacology of Natural Products & Clinical Pharmacology,
University of Ulm, Ulm, Germany.
In this study we investigated the effects of concomitant food intake on the
bioavailability of distinct boswellic acids (BAs) from the test preparation
BSE/018, a dry extract from Boswellia serrata gum resin. In a randomised, open,
single/dose, two/way crossover study, healthy male subjects received three
capsules of BSE/018 equivalent to 786 mg dry extract of Boswellia serrata gum
resin either in the fasted state or together with a standardised high/fat meal.
BA plasma concentrations were analysed for up to 60 h after oral dosing by
reversed phase HPLC. As compared to the fasted state (treatment A), the
administration of BSE/018 concomitantly with a high/fat meal (treatment B) led
to several/fold increased areas under the plasma concentration/time curves as
well as peak concentrations of beta/boswellic acid (betaBA),
11/keto/beta/boswellic acid (KbetaBA) and acetyl/11/keto/beta/boswellic acid
(AKbetaBA). Plasma levels of both acetyl/alpha/boswellic acid (AalphaBA) and
alphaBA became only detectable when administered with treatment B, i.e., the
high/fat meal. Accordingly, pharmacokinetic data could be calculated for betaBA,
KbetaBA and AKbetaBA (treatment A) and for betaBA, KbetaBA, AKbetaBA, alphaBA,
and AalphaBA (treatment B). For the first time these data reveal detailed
kinetics of BAs after oral dosing of an extract and demonstrate a profound
effect of food intake on the pharmacokinetic profile of the BAs. This finding
should be very important whenever BAs would be considered for therapeutic use.
Publication Types:
Clinical Trial
Randomized Controlled Trial
PMID: 15643550 [PubMed / indexed for MEDLINE]
27: Am J Physiol Gastrointest Liver Physiol. 2005 Apr;288(4):G798/808. Epub 2004
Nov 11.
Effects of Boswellia serrata in mouse models of chemically induced colitis.
Kiela PR, Midura AJ, Kuscuoglu N, Jolad SD, Solyom AM, Besselsen DG, Timmermann
BN, Ghishan FK.
Dept. of Pediatrics, Children's Research Center, Univ. of Arizona, 1501 N.
Campbell Ave., Tucson, AZ 85724, USA. pkiela@peds.arizona.edu
Extracts from Boswellia serrata have been reported to have anti/inflammatory
activity, primarily via boswellic acid/mediated inhibition of leukotriene
synthesis. In three small clinical trials, boswellia was shown to improve
symptoms of ulcerative colitis and Crohn's disease, and because of its alleged
safety, boswellia was considered superior over mesalazine in terms of a
benefit/risk evaluation. The goal of this study was to evaluate the
effectiveness of boswellia extracts in controlled settings of dextran sulfate/
or trinitrobenzene sulfonic acid/induced colitis in mice. Our results suggest
that boswellia is ineffective in ameliorating colitis in these models. Moreover,
individual boswellic acids were demonstrated to increase the basal and
IL/1beta/stimulated NF/kappaB activity in intestinal epithelial cells in vitro
as well as reverse proliferative effects of IL/1beta. We also observed
hepatotoxic effect of boswellia with pronounced hepatomegaly and steatosis.
Hepatotoxity and increased lipid accumulation in response to boswellia were
further confirmed in vitro in HepG2 cells with fluorescent Nile red
binding/resazurin reduction assay and by confocal microscopy. Microarray
analyses of hepatic gene expression demonstrated dysregulation of a number of
genes, including a large group of lipid metabolism/related genes, and
detoxifying enzymes, a response consistent with that to hepatotoxic xenobiotics.
In summary, boswellia does not ameliorate symptoms of colitis in chemically
induced murine models and, in higher doses, may become hepatotoxic. Potential
implications of prolonged and uncontrolled intake of boswellia as an herbal
supplement in inflammatory bowel disease and other inflammatory conditions
should be considered in future clinical trials with this botanical.
Publication Types:
Research Support, U.S. Gov't, P.H.S.
PMID: 15539433 [PubMed / indexed for MEDLINE]
28: Contact Dermatitis. 2004 Aug;51(2):91/2.
Allergic contact dermatitis from Boswellia serrata extract in a naturopathic
cream.
Acebo E, Raton JA, Sautua S, Eizaguirre X, Trebol I, Perez JL.
Department of Dermatology, Hospital de Cruces, Bilbao, Spain.
Publication Types:
Case Reports
PMID: 15373853 [PubMed / indexed for MEDLINE]
29: Indian J Exp Biol. 2003 Dec;41(12):1460/2.
Immunomodulatory activity of boswellic acids of Boswellia serrata Roxb.
Pungle P, Banavalikar M, Suthar A, Biyani M, Mengi S.
C. U. Shah College of Pharmacy, Sir Vithaldas Vidya Vihar, SNDT Women's
University, Juhu, Santacruz (W), Mumbai 400 049, India.
Extract of gum resin of B. serrata containing 60% acetyl 11/keto beta boswellic
acid (AKBA) along with other constituents such as 11/keto beta/boswellic acid
(KBA), acetyl beta/boswellic acid and beta/boswellic acid has been evaluated for
antianaphylactic and mast cell stabilizing activity using passive paw
anaphylaxis and compound 48/80 induced degranulation of mast cell methods. The
extract inhibited the passive paw anaphylaxis reaction in rats in dose/dependant
manner (20, 40 and 80 mg/kg, po). However, the standard dexamethasone (0.27
mg/kg, po) revealed maximum inhibition of edema as compared to the extract. A
significant inhibition in the compound 48/80 induced degranulation of mast cells
in dose/dependant manner (20, 40 and 80 mg/kg, po) was observed thus showing
mast cell stabilizing activity. The standard disodium cromoglycate (50 mg/kg,
ip) was found to demonstrate maximum per cent protection against degranulation
as compared to the extract containing 60% AKBA. The results suggest promising
antianaphylactic and mast cell stabilizing activity of the extract.
PMID: 15320503 [PubMed / indexed for MEDLINE]
30: Inflammopharmacology. 2004;12(2):131/52.
Anti/inflammatory properties of BHUx, a polyherbal formulation to prevent
atherosclerosis.
Tripathi YB, Reddy MM, Pandey RS, Subhashini J, Tiwari OP, Singh BK, Reddanna P.
Department of Medicinal Chemistry, Institute of Medical Sciences, Banaras Hindu
University, Varanasi/221005, India. Yamini30@sify.com
BHUx is a polyherbal formulation consisting of water/soluble fractions of five
medicinal plants (Commiphora mukul, Terminalia arjuna, Boswellia serrata,
Semecarpus anacardium and Strychnos nux vomica). The present study was
undertaken to evaluate its antioxidant and antiinflammatory effects. BHUx,
standardized by HPLC fingerprinting and filtered through 0.2 microm filter
paper, was employed for different studies under in vivo and in vitro conditions.
Under in vivo conditions, BHUx significantly reduced inflammation in the
carrageenan/induced rat paw oedema model of inflammation, suggesting its
anti/inflammatory properties. In order to test the mechanism of action of BHUx,
further in vitro studies were undertaken on cumene/hydroperoxide/induced lipid
peroxidation (CHP) in liver homogenate, LPS/induced NO production in peritoneal
macrophages and on key enzymes of arachidonic acid cascade, involved in the
mediation of inflammation. Under the conditions, BHUx showed
concentration/dependent inhibition of CHP/induced lipid peroxidation in liver
homogenate, suggesting its antioxidant properties. Similarly the potent
anti/inflammatory effects of BHUx are evident by (a) preferential inhibition of
COX/2 (IC50 for COX/2 = 80 microg/ml and IC50 for COX/1 = 169 microg/ml), (b)
low ratios in the IC50 values of COX/2/COX/1 (0.47), (c) decreased production of
NO in LPS/induced peritoneal macrophages and (d) inhibition of 5/LOX (IC50 = 795
microg/ml). BHUx also showed a preference for inhibiting 15/lipoxygenase (IC50 =
44 microg/ml), a key enzyme implicated in LDL oxidation. These studies suggest
that BHUx is acting mainly at three levels, i.e., as a potent natural
antioxidant, by reduction of key inflammatory mediators of arachidonic acid
cascade and by preventing 15/LOX/mediated LDL oxidations, to prevent
atherosclerosis.
Publication Types:
Comparative Study
Research Support, Non/U.S. Gov't
PMID: 15265316 [PubMed / indexed for MEDLINE]
31: Phytomedicine. 2004 Feb;11(2/3):255/60.
Pharmacokinetic study of 11/Keto beta/Boswellic acid.
Sharma S, Thawani V, Hingorani L, Shrivastava M, Bhate VR, Khiyani R.
Pharmacology, Indira Gandhi Medical College, Nagpur, India.
INTRODUCTION: Boswellia serrata has been used in traditional medicine for
treatment of inflammatory diseases since antiquity. However human kinetic
studies are lacking for this. Hence to better elucidate its effects in humans
and determine its optimal dosing, this study was planned. MATERIAL AND METHODS:
Twelve healthy adult men volunteers were given capsule Wok Vel containing 333 mg
of Boswellia Serrata Extract, orally, after a seven days washout period. Venous
blood samples were drawn through indwelling canula from each volunteer prior to
drug administration and at 30, 60, 120, 150, 180, 210, 240, 300, 360, 480, 600,
720, 840 minutes after drug administration. Plasma obtained after centrifuge was
analyzed to measure concentration of 11/Keto beta/Boswellic Acid (KBA) by HPLC.
Various kinetic parameters were then calculated from the plasma concentrations.
RESULTS: The results are expressed as mean +// Standard Error of Mean. The peak
plasma levels (2.72 x 10(/3) +// 0.18 micromoles/ml) of BSE were reached at 4.5
+// 0.55 h. The concentration declined with a mean elimination half life of 5.97
+// 0.95 h. The apparent volume of distribution averaged 142.87 +// 22.78 L and
the plasma clearance was 296.10 +// 24.09 ml/min. The AUC(0/infinity) was 27.33
x 10(/3) +// 1.99 micromoles/ml h. CONCLUSION: Elimination half life of nearly
six hours suggests that the drug needs to be given orally at the interval of six
hours. The plasma concentration will attain the steady state after approximately
30 hours. BSE is a safe drug and well tolerated on oral administration. No
adverse effects were seen with this drug when administered as single dose in 333
mg.
PMID: 15070181 [PubMed / indexed for MEDLINE]
32: Schweiz Arch Tierheilkd. 2004 Feb;146(2):71/9.
Dietary support with Boswellia resin in canine inflammatory joint and spinal
disease.
Reichling J, Schmokel H, Fitzi J, Bucher S, Saller R.
Institut fur Pharmazie und Molekulare Biotechnologie (IPMB), Abteilung Biologie,
Ruprecht/Karls/University Heidelberg, Germany. Juergen.Reichling@t/online.de
An open multi/centre veterinary clinical trial, comparing conditions before and
after treatment with a herbal dietary supplement consisting of a natural resin
extract of Boswellia serrata, was conducted by 10 practicing veterinarians in
Switzerland. This traditional plant/based supplement is known for its
anti/rheumatic and anti/inflammatory properties. 29 dogs with manifestations of
chronic joint and spinal disease were enrolled. Osteoarthritis and degenerative
conditions were confirmed radiologically in 25 of 29 cases. The resin extract
(BSB108, product of Bogar AG) was administered with the regular food at a dose
of 400 mg/10 kg body weight once daily for 6 weeks. Already after two weeks of
treatment, an overall efficacy of the dietary supplement was evident in 71% of
24 eligible dogs. A statistically significant reduction of severity and
resolution of typical clinical signs in individual animals, such as intermittent
lameness, local pain and stiff gait, were reported after 6 weeks. Effects of
external factors that aggravate lameness, such as "lameness when moving" and
"lameness after a long rest" diminished gradually. In 5 dogs, reversible brief
episodes of diarrhea and flatulence occurred, but only once was a relationship
to the study preparation suspected. Because quality and stability of the resin
extract were ensured, these data suggest that a standardized preparation can be
recommended as a herbal dietary supplement providing symptomatic support in
canine osteoarthritic disease.
Publication Types:
Clinical Trial
Multicenter Study
Research Support, Non/U.S. Gov't
PMID: 14994484 [PubMed / indexed for MEDLINE]
33: Br J Pharmacol. 2004 Jan;141(2):223/32. Epub 2003 Dec 22.
Coupling of boswellic acid/induced Ca2+ mobilisation and MAPK activation to
lipid metabolism and peroxide formation in human leucocytes.
Altmann A, Poeckel D, Fischer L, Schubert/Zsilavecz M, Steinhilber D, Werz O.
Institute of Pharmaceutical Chemistry, University of Frankfurt, Marie/Curie
Strasse 9, Frankfurt D/60439, Germany.
1. We have previously shown that 11/keto boswellic acids (11/keto/BAs), the
active principles of Boswellia serrata gum resins, activate p38 MAPK and
p42/44(MAPK) and stimulate Ca(2+) mobilisation in human polymorphonuclear
leucocytes (PMNL). 2. In this study, we attempted to connect the activation of
MAPK and mobilisation of Ca(2+) to functional responses of PMNL, including the
formation of reactive oxygen species (ROS), release of arachidonic acid (AA),
and leukotriene (LT) biosynthesis. 3. We found that, in PMNL, 11/keto/BAs
stimulate the formation of ROS and cause release of AA as well as its
transformation to LTs via 5/lipoxygenase. 4. Based on inhibitor studies,
11/keto/BA/induced ROS formation is Ca(2+)/dependent and is mediated by NADPH
oxidase involving PI 3/K and p42/44(MAPK) signalling pathways. Also, the release
of AA depends on Ca(2+) and p42/44(MAPK), whereas the pathways stimulating 5/LO
are not readily apparent. 5. Pertussis toxin, which inactivates G(i/0) protein
subunits, prevents MAPK activation and Ca(2+) mobilisation induced by
11/keto/BAs, implying the involvement of a G(i/0) protein in BA signalling. 6.
Expanding studies on differentiated haematopoietic cell lines (HL60, Mono Mac 6,
BL41/E/95/A) demonstrate that the ability of BAs to activate MAPK and to
mobilise Ca(2+) may depend on the cell type or the differentiation status. 7. In
summary, we conclude that BAs act via G(i/0) protein(s) stimulating signalling
pathways that control functional leucocyte responses, in a similar way as
chemoattractants, that is, N/formyl/methionyl/leucyl/phenylalanine or
platelet/activating factor.
Publication Types:
Comparative Study
Research Support, Non/U.S. Gov't
PMID: 14691050 [PubMed / indexed for MEDLINE]
34: Adv Exp Med Biol. 2002;507:387/93.
Acetyl/11/keto/beta/boswellic acid (AKBA) is cytotoxic for meningioma cells and
inhibits phosphorylation of the extracellular/signal regulated kinase 1 and 2.
Park YS, Lee JH, Harwalkar JA, Bondar J, Safayhi H, Golubic M.
Department of Neurosurgery, Cleveland Clinic Foundation, 9500 Euclid
Avenue/NB2/120A, Cleveland, OH 44195, USA.
Acetyl/11/keto/beta/boswellic acid (AKBA) is a naturally occurring pentacyclic
triterpene isolated from the gum resin exudate from the stem of the tree
Boswellia serrata (frankincense). AKBA has been recently identified as a novel,
orally active, non/redox and non/competitive 5/lipoxygenase inhibitor that also
inhibits topisomerase I and II in vitro. Because natural pentacyclic triterpenes
have an antiproliferative effect against different tumor types, we investigated
the effects of AKBA on the proliferation of 11 primary cell cultures established
from human surgical specimens of meningiomas, common central nervous system
tumors. Treatment of meningioma cells by AKBA revealed a potent cytotoxic
activity with half/maximal inhibitory concentrations in the range of 2/8 microM.
At similar, physiologically achievable concentrations, AKBA rapidly (within
minutes) and potently inhibited the phosphorylation of extracellular
signal/regulated kinase 1 and 2 (Erk/1 and Erk/2) in meningioma cells stimulated
with platelet/derived growth factor BB. High expression level of 5/LO was
detected in primary meningioma cells and surgical specimens by immunoblotting
analysis, suggesting the possible role of 5/LO in meningioma tumorigenesis.
Considering the critical importance of the Erk/1/2 signal transduction pathway
not only in meningiomas but in other human neoplasms, the interruption of
signaling through this evolutionarily conserved pathway might be one of the
mechanisms by which AKBA induces suppression of proliferation and apoptosis of
different tumor types.
Publication Types:
Research Support, Non/U.S. Gov't
PMID: 12664615 [PubMed / indexed for MEDLINE]
35: Phytomedicine. 2003 Jan;10(1):3/7.
Efficacy and tolerability of Boswellia serrata extract in treatment of
osteoarthritis of knee//a randomized double blind placebo controlled trial.
Kimmatkar N, Thawani V, Hingorani L, Khiyani R.
MS Orthopedics, Indira Gandhi Medical College, Nagpur, India.
Osteoarthritis is a common, chronic, progressive, skeletal, degenerative
disorder, which commonly affects the knee joint. Boswellia serrata tree is
commonly found in India. The therapeutic value of its gum (guggulu) has been
known. It posses good anti/inflammatory, anti/arthritic and analgesic activity.
A randomized double blind placebo controlled crossover study was conducted to
assess the efficacy, safety and tolerability of Boswellia serrata Extract (BSE)
in 30 patients of osteoarthritis of knee, 15 each receiving active drug or
placebo for eight weeks. After the first intervention, washout was given and
then the groups were crossed over to receive the opposite intervention for eight
weeks. All patients receiving drug treatment reported decrease in knee pain,
increased knee flexion and increased walking distance. The frequency of swelling
in the knee joint was decreased. Radiologically there was no change. The
observed differences between drug treated and placebo being statistically
significant, are clinically relevant. BSE was well tolerated by the subjects
except for minor gastrointestinal ADRs. BSE is recommended in the patients of
osteoarthritis of the knee with possible therapeutic use in other arthritis.
Publication Types:
Clinical Trial
Randomized Controlled Trial
PMID: 12622457 [PubMed / indexed for MEDLINE]
36: Anticancer Res. 2002 Sep/Oct;22(5):2853/62.
Cytostatic and apoptosis/inducing activity of boswellic acids toward malignant
cell lines in vitro.
Hostanska K, Daum G, Saller R.
Departmment of Internal Medicine, University Hospital Zurich, Ramistrasse 100,
8091 Zurich, Switzerland. katarina.hostanska@access.unizh.ch
Boswellic acids from frankincense were indentified as the active compounds which
inhibit leukotriene biosynthesis, 5/lipoxygenase and exert antiproliferative
activity toward a variety of malignant cells. Because of the relevance for the
clinical application, we tested the ethanolic extract of Boswellia serrata gum
resin containing a defined amount of boswellic acids for its cytotoxic,
cytostatic and apoptotic activity on five leukemia (HL/60, K 562, U937, MOLT/4,
THP/1) and two brain tumor (LN/18, LN/229) cell lines by WST/1 assay and flow
cytometry. The Boswellia serrata extract induced dose/dependent
antiproliferative effects on all human malignant cells tested with GI50 values
(extract concentration producing 50% cell growth inhibition) between 57.0 and
124.1 micrograms/ml. In three haematological cell lines (K562, U937, MOLT/4) the
effect of total extract expressed in GI50 was 2.8/, 3.3/ and 2.3/times more
potent (p < 0.05) than pure 3/O/acetyl/11/keto/beta/boswellic acid (AKBA).
Morphological changes after 24/27 hours and the detection of apoptotic cells by
AnnexinV/binding and/or by the detection of propidium iodide/labelled DNA with
flow cytometry, confirmed the apoptotic cell death. The results of this study
suggest the effectiveness of Boswellia serrata extract with defined content of
boswellic acids.
PMID: 12530009 [PubMed / indexed for MEDLINE]
37: Carcinogenesis. 2002 Dec;23(12):2087/93.
Boswellic acids trigger apoptosis via a pathway dependent on caspase/8
activation but independent on Fas/Fas ligand interaction in colon cancer HT/29
cells.
Liu JJ, Nilsson A, Oredsson S, Badmaev V, Zhao WZ, Duan RD.
Cell Biology B, Biomedical Center, B11, Lund University, Sweden.
Boswellic acids are the effective components of gum resin of Boswellia serrata,
which has anti/inflammatory properties. Recent studies on brain tumors and
leukemic cells indicate that boswellic acids may have antiproliferative and
apoptotic effects with the mechanisms being not studied in detail. We studied
their antiproliferative and apoptotic effects on colon cancer cells and the
pathway leading to apoptosis. HT/29 cells were treated with beta/boswellic acid
(BA), keto/beta/boswellic acid (K/BA) and acetyl/keto/beta/boswellic acid
(AK/BA), respectively. Apoptosis was determined by flow cytometry, by
cytoplasmic DNA/histone complex and the activity of caspase/3. The cleavage of
poly/(ADP/ribose)/polymerase (PARP) and expression of Fas were examined by
western blot. Specific caspase inhibitors, polyclonal Fas antibody, and
antagonistic Fas antibody ZB4 were employed to elucidate apoptotic pathways. DNA
synthesis and cell viability were examined. Both K/BA and AK/BA increased
cytoplasmic DNA/histone complex dose/dependently and increased pre/G(1) peak in
flow cytometer analysis, with the effects of AK/BA being stronger than K/BA. BA
only increased the formation of DNA/histone complex at a high concentration.
K/BA and AK/BA increased caspase/8, caspase/9 and caspase/3 activities
accompanied by cleavage of PARP. The effects of AK/BA on formation of
cytoplasmic DNA histone and on caspase/3 activation were 3.7/ and 3.4/fold,
respectively, more effective than those induced by camptothecin. The apoptosis
induced by AK/BA was inhibited completely by caspase/3 or caspase/8 inhibitor
and partially by caspase/9 inhibitor. ZB4 blocked exogenous Fas ligand/induced
apoptosis, but had no effect on AK/BA/induced apoptosis. AK/BA had no
significant effect on expression of Fas. Apart from apoptotic effect, these
acids also inhibited [(3)H]thymidine incorporation and cell viability to
different extent. In conclusion, boswellic acids, particularly AK/BA and K/BA
have antiproliferative and apoptotic effects in human HT/29 cells. The apoptotic
effect is mediated via a pathway dependent on caspase/8 activation but
independent of Fas/FasL interaction.
Publication Types:
Research Support, Non/U.S. Gov't
PMID: 12507932 [PubMed / indexed for MEDLINE]
38: Wien Med Wochenschr. 2002;152(15/16):373/8.
[Boswellic acids (components of frankincense) as the active principle in
treatment of chronic inflammatory diseases]
[Article in German]
Ammon HP.
Lehrstuhl Pharmakologie fur Naturwissenschaftler, Pharmazeutisches Institut der
Universitat Tubingen, Deutschland. sekretariat.ammon@uni/tuebingen.de
Preparations from the gum resin of Boswellia serrata have been used as a
traditional remedy in Ayurvedic medicine in India for the treatment of
inflammatory diseases. Compounds from the gum with genuine antiinflammatory
effects are pentacyclic triterpenes of the boswellic acid type. Boswellic acids
inhibit the leukotriene biosynthesis in neutrophilic granulocytes by a
non/redox, noncompetitive inhibition of 5/lipoxygenase. The effect is triggered
by boswellic acids binding to the enzyme. Moreover certain boswellic acids have
been described to inhibit elastase in leukocytes, to inhibit proliferation,
induce apoptosis and to inhibit topoisomerases of leukoma/ and glioma cell
lines. A series of chronic inflammatory diseases are thought to be perpetuated
by leukotrienes. In clinical trials promising results were observed in patients
with rheumatoid arthritis, chronic colitis, ulcerative colitis, Crohn's disease,
bronchial asthma und peritumoral brains edemas.
Publication Types:
English Abstract
Review
PMID: 12244881 [PubMed / indexed for MEDLINE]
39: Int J Mol Med. 2002 Oct;10(4):501/5.
Keto/ and acetyl/keto/boswellic acids inhibit proliferation and induce apoptosis
in Hep G2 cells via a caspase/8 dependent pathway.
Liu JJ, Nilsson A, Oredsson S, Badmaev V, Duan RD.
Biomedical Center, B11, Lund University, S/22184 Lund, Sweden.
Boswellic acids are the compounds isolated from the gum resin of Boswellia
serrata and have been used for the treatment of inflammatory diseases for many
years in the countries of the east. Recently, a few studies showed that the
acids may have anti/cancer effect on leukemia and brain tumours. We investigated
the apoptotic and anti/proliferative effects of two types of boswellic acids,
keto/beta/boswellic acid and acetyl/keto/beta/boswellic acid, on liver cancer
Hep G2 cells. After treating the cells with the boswellic acids, cell
proliferation, DNA synthesis, and apoptosis were analysed. The activities of
caspase/3, /8 and /9 were assayed. To explore the apoptotic pathway, specific
caspase inhibitors were employed. It was found that boswellic acids decreased
cell viability and [3H]thymidine incorporation, checked the cells in the G1
phase, and increased percentage of sub/G1. Boswellic acids strongly induced
apoptosis accompanied by activation of caspase/3, /8 and /9. The apoptosis was
blocked completely by caspase/8 or caspase/3 inhibitor, but inhibited partly by
caspase/9 inhibitor. However, these caspase inhibitors did not show any effect
on the alternations of cell viability caused by boswellic acids. In conclusion,
boswellic acids have anti/proliferation and anti/cancer effects on Hep G2 cells.
The apoptotic effect is mediated by a pathway dependent on caspase/8 activation.
The acids may be a promising drug for the chemoprevention of liver cancer.
Publication Types:
Research Support, Non/U.S. Gov't
PMID: 12239601 [PubMed / indexed for MEDLINE]
40: Planta Med. 2002 May;68(5):397/401.
Cytotoxic action of acetyl/11/keto/beta/boswellic acid (AKBA) on meningioma
cells.
Park YS, Lee JH, Bondar J, Harwalkar JA, Safayhi H, Golubic M.
Cleveland Clinic Foundation, Department of Neurosurgery, Cleveland, OH 44195,
USA.
Acetyl/11/keto/beta/boswellic acid (AKBA) is a naturally occurring pentacyclic
triterpene isolated from the gum resin exudate of the tree Boswellia serrata
(frankincense). Because pentacyclic triterpenes have antiproliferative and
cytotoxic effects against different tumor types, we investigated whether AKBA
would act in a similar fashion on primary human meningioma cell cultures.
Primary cell cultures were established from surgically removed meningioma
specimens. The number of viable cells in the absence/presence of AKBA was
determined by the non/radioactive cell proliferation assay. The activation
status of the proliferative cell marker, extracellular signal/regulated kinase/1
and /2 (Erk/1 and Erk/2) was determined by immunoblotting with the antibody that
recognizes the activated form of these proteins. Treatment of meningioma cells
by AKBA revealed a potent cytotoxic activity with half/maximal inhibitory
concentrations in the range of 2 / 8 microM. At low micromolar concentrations,
AKBA rapidly and potently inhibited the phosphorylation of Erk/1/2 and impaired
the motility of meningioma cells stimulated with platelet/derived growth factor
BB. The cytotoxic action of AKBA on meningioma cells may be mediated, at least
in part, by the inhibition of the Erk signal transduction pathway. Because of
the central role the Erk pathway plays in signal transduction and tumorigenesis,
further investigation into the potential clinical use for AKBA and related
boswellic acids is warranted.
Publication Types:
Research Support, Non/U.S. Gov't
PMID: 12058313 [PubMed / indexed for MEDLINE]
41: Indian J Exp Biol. 2001 Oct;39(10):1068/70.
Clastogenic effects of dietary supplement//Spirulina alga, and some medicinal
plant products from Boswellia serrata, Withania somnifera on mice.
Ghoshal S, Mukhopadhyay MJ, Mukherjee A.
Centre of Advanced Study in Cell and Chromosome Research, Department of Botany,
University of Calcutta, Kolkata, India.
Pretreatment of aqueous extracts of Zyrulina (Spirulina), Aswagandha (Withania)
and Nopane (Boswellia) on colchicine induced chromosome damage showed weakness
of clastogenic activity in Swiss albino mice. None of the treatments increased
significantly the number of chromosome aberrations.
Publication Types:
Research Support, Non/U.S. Gov't
PMID: 11883518 [PubMed / indexed for MEDLINE]
42: Phytochem Anal. 2001 Nov/Dec;12(6):374/6.
High/performance thin layer chromatographic analysis of anti/inflammatory
triterpenoids from Boswellia serrata Roxb.
Krohn K, Rao MS, Raman NV, Khalilullah M.
Universitat Paderborn, Fachbereich Chemie und Chemietechnik, 33098 Paderborn,
Germany. kk@chemie.uni/paderborn.de
A rapid and simple high/performance thin layer chromatographic (HPTLC) method
was developed for the simultaneous quantitative estimation of the biologically
active triterpenoids beta/boswellic acid, 3/O/acetyl/beta/boswellic acid,
11/keto/beta/boswellic acid and 3/O/acetyl/11/keto/beta/boswellic acid from the
gum resin of Boswellia serrata. The assay combines the isolation and separation
of boswellic acid derivatives on silica gel 60F254/HPTLC plates with spot
visualisation and scanning at 250 nm. Methanol was found to be the most
appropriate solvent for the exhaustive extraction of boswellic acid derivatives.
PMID: 11793815 [PubMed / indexed for MEDLINE]
43: Biochem Biophys Res Commun. 2002 Jan 11;290(1):185/90.
Boswellic acids activate p42(MAPK) and p38 MAPK and stimulate Ca(2+)
mobilization.
Altmann A, Fischer L, Schubert/Zsilavecz M, Steinhilber D, Werz O.
Institute of Pharmaceutical Chemistry, University of Frankfurt, Marie/Curie
Strasse 9, D/60439 Frankfurt, Germany.
Here we show that extracts of Boswellia serrata gum resins and its constituents,
the boswellic acids (BAs), activate the mitogen/activated protein kinases (MAPK)
p42(MAPK) and p38 in isolated human polymorphonuclear leukocytes (PMNL). MAPK
activation was rapid and transient with maximal activation after 1/2.5 min of
exposure and occurred in a dose/dependent manner. The keto/BAs (11/keto/beta/BA
and 3/O/acetyl/11/beta/keto/BA) gave substantial kinase activation at 30 microM,
whereas other BAs lacking the 11/keto group were less effective. Moreover,
11/keto/BAs induced rapid and prominent mobilization of free Ca(2+) in PMNL.
Inhibitor studies revealed that phosphatidylinositol 3/kinase (PI 3/K) is
involved in BA/induced MAPK activation, whereas a minor role was apparent for
protein kinase C. MAPK activation by 3/O/acetyl/11/beta/keto/BA was partially
inhibited when Ca(2+) was removed by chelation. Our results suggest that
11/keto/BAs might function as potent activators of PMNL by stimulation of MAPK
and mobilization of intracellular Ca(2+). (c)2002 Elsevier Science.
Publication Types:
Research Support, Non/U.S. Gov't
PMID: 11779151 [PubMed / indexed for MEDLINE]
44: Planta Med. 2001 Nov;67(8):778/80.
A reversed phase high performance liquid chromatography method for the analysis
of boswellic acids in Boswellia serrata.
Ganzera M, Khan IA.
National Center for Natural Products Research, Research Institute of
Pharmaceutical Sciences, The University of Mississippi, University, Mississippi
38677, USA.
An HPLC method for the separation of boswellic acids, the active constituents in
Boswellia serrata resin has been developed. The first accurate determination of
6 individual acids was possible in the resin as well as in multi/component
preparations. By using an acidic mobile phase, raised temperature and a 4 microm
Synergi MAX/RP 80 A column the acids could be detected at levels as low as 0.9
microg/ml. The study of market products revealed significant variations in the
content of these pharmacologically active compounds in commercial samples.
Publication Types:
Research Support, Non/U.S. Gov't
Research Support, U.S. Gov't, Non/P.H.S.
PMID: 11731931 [PubMed / indexed for MEDLINE]
45: Planta Med. 2001 Jul;67(5):391/5.
Effects of gum resin of Boswellia serrata in patients with chronic colitis.
Gupta I, Parihar A, Malhotra P, Gupta S, Ludtke R, Safayhi H, Ammon HP.
Department of Medicine, Medical College Jammu, J&K, India.
Patients studied here suffered from chronic colitis characterized by vague lower
abdominal pain, bleeding per rectum with diarrhoea and palpable tender
descending and sigmoid colon. The inflammatory process in colitis is associated
with increased formation of leukotrienes causing chemotaxis, chemokinesis,
synthesis of superoxide radicals and release of lysosomal enzymes by phagocytes.
The key enzyme for leukotriene biosynthesis is 5/lipoxygenase. Boswellic acids
were found to be non/redox, non/competitive specific inhibitors of the enzyme
5/lipoxygenase. We studied the gum resin of Boswellia serrata for the treatment
of this disease. Thirty patients, 17 males and 13 females in the age range of 18
to 48 years with chronic colitis were included in this study. Twenty patients
were given a preparation of the gum resin of Boswellia serrata (900 mg daily
divided in three doses for 6 weeks) and ten patients were given sulfasalazine (3
gm daily divided in three doses for 6 weeks) and served as controls. Out of 20
patients treated with Boswellia gum resin 18 patients showed an improvement in
one or more of the parameters: including stool properties, histopathology as
well as scanning electron microscopy, besides haemoglobin, serum iron, calcium,
phosphorus, proteins, total leukocytes and eosinophils. In the control group 6
out of 10 patients showed similar results with the same parameters. Out of 20
patients treated with Boswellia gum resin 14 went into remission while in case
of sulfasalazine remission rate was 4 out of 10. In conclusion, this study shows
that a gum resin preparation from Boswellia serrata could be effective in the
treatment of chronic colitis with minimal side effects.
Publication Types:
Clinical Trial
Comparative Study
Randomized Controlled Trial
PMID: 11488449 [PubMed / indexed for MEDLINE]
46: Mol Pharmacol. 2001 Aug;60(2):267/73.
Stimulation of leukotriene synthesis in intact polymorphonuclear cells by the
5/lipoxygenase inhibitor 3/oxo/tirucallic acid.
Boden SE, Schweizer S, Bertsche T, Dufer M, Drews G, Safayhi H.
Department of Pharmacology, Institute of Pharmaceutical Sciences, University of
Tubingen, Tubingen, Germany.
Commercially available extracts from Boswellia serrata resin used as
anti/inflammatory drugs or phytonutrients show paradoxical
concentration/dependent potentiating and inhibitory actions on 5/lipoxygenase
(5/LO) product synthesis in stimulated PMNs. In our attempt to characterize the
stimulating constituents, we identified the tetracyclic triterpene
3/oxo/tirucallic acid (3/oxo/TA), which, in the range from 2.5 to 15 microM,
enhanced 5/LO product formation in ionophore/challenged polymorphonuclear cells
(PMNs) (e.g., from 1981 +// 177 to 3042 +// 208 pmol at 10 microM 3/oxo/TA), and
initiated Ca(2+) mobilization, MEK/1/2 phosphorylation, 5/LO translocation, and
5/LO product formation in resting cells (534 +// 394 pmol/5 x 10(6) PMNs). In
cell/free 5/LO assays, 3/oxo/TA acted only inhibitory (IC(50) value of about 3
microM), demonstrating the pivotal role of intact cell structure for its
activating property. In 3/oxo/TA/challenged PMNs, the mitogen/activated protein
kinase kinase (MEK)/1/2 inhibitor PD098059 abolished 5/LO product formation,
along with inhibition of MEK/1/2 phosphorylation and 5/LO translocation. The
3/acetoxy derivative of 3/oxo/TA acted like 3/oxo/TA in intact PMNs, whereas
3/hydroxy/TA barely stimulated MEK phosphorylation in resting cells and showed
only inhibition on ionophore/induced 5/LO product synthesis. Steroid/type
tetracycles neither induced 5/LO activation nor had enhancing or inhibitory
effects. In summary, defined natural tetracyclic triterpenes, which act as
inhibitors of the 5/LO in the cell/free assay, initiate 5/LO activation by a
MEK/inhibitor sensitive mechanism and potentiate stimulated product synthesis in
intact cells. Because TAs contribute significantly to the overall biological
effects of B. serrata resin extracts, special precaution for standardization is
recommended when using B. serrata preparations as drugs or dietary supplements.
Publication Types:
Research Support, Non/U.S. Gov't
PMID: 11455013 [PubMed / indexed for MEDLINE]
47: Int J Colorectal Dis. 2001 Apr;16(2):88/95.
Acetyl/11/keto/beta/boswellic acid, a constituent of a herbal medicine from
Boswellia serrata resin, attenuates experimental ileitis.
Krieglstein CF, Anthoni C, Rijcken EJ, Laukotter M, Spiegel HU, Boden SE,
Schweizer S, Safayhi H, Senninger N, Schurmann G.
Department of General Surgery, Westfalian Wilhelm's University, Waldeyerstrasse
1, 48149 Munster, Germany. kriegls@uni/muenster.de
The gum resin extract from Boswellia serrata (H15), an herbal product, was
recently shown to have positive therapeutic effects in inflammatory bowel
disease (IBD). However, the mechanisms and constituents responsible for these
effects are poorly understood. This study examined the effect of the Boswellia
extract and its single constituent acetyl/11/keto/beta/boswellic acid (AKBA) on
leukocyte/endothelial cell interactions in an experimental model of IBD. Ileitis
was induced by two subcutaneous injections of indomethacin (7.5 mg/kg) in
Sprague/Dawley rats 24 h apart. Rats also received oral treatment with the
Boswellia extract (H15) or AKBA at two different doses (low and high) equivalent
to recommendations in human disease over 2 days. Controls received only the
carriers NaHCO3 (subcutaneously) and tylose (orally). Effects of treatment were
assessed by intravital microscopy in ileal submucosal venules for changes in the
number of rolling and adherent leukocytes and by macroscopic and histological
scoring. Increased leukocyte/endothelial cell adhesive interactions and severe
tissue injury accompanied indomethacin/induced ileitis. Treatment with the
Boswellia extract or AKBA resulted in a dose/dependent decrease in rolling (up
to 90%) and adherent (up to 98%) leukocytes. High/dose Boswellia extract as well
as both low/ and high/dose AKBA significantly attenuated tissue injury scores.
Oral therapy with the Boswellia extract or AKBA significantly reduces
macroscopic and microcirculatory inflammatory features normally associated with
indomethacin administration, indicating that the anti/inflammatory actions of
the Boswellia extract in IBD may be due in part to boswellic acids such as AKBA.
Publication Types:
Comparative Study
Research Support, Non/U.S. Gov't
PMID: 11355324 [PubMed / indexed for MEDLINE]
48: Biofactors. 2000;13(1/4):225/30.
Anti/tumor and anti/carcinogenic activities of triterpenoid, beta/boswellic
acid.
Huang MT, Badmaev V, Ding Y, Liu Y, Xie JG, Ho CT.
Laboratory for Cancer Research, College of Pharmacy, Rutgers University,
Piscataway, NJ 08854/8020, USA. mthuang@rci.rutgers.edu
Boswellin (BE), a methanol extract of the gum resin exudate of Boswellia
serrata, contains naturally occurring triterpenoids, beta/boswellic acid and its
structural related derivatives, has been used as a traditional medicine for the
treatment of inflammatory and arthritic diseases. Topical application of BE to
the backs of mice markedly inhibited 12/O/tetradecanoylphorbol/13/acetate
(TPA)/induced increases in skin inflammation, epidermal proliferation, the
number of epidermal cell layers, and tumor promotion in
7,12/dimethylbenz[a]anthracene (DMBA)/initiated mice. Feeding 0.2% of BE in the
diet to CF/1 mice for 10/24 weeks reduced the accumulation of parametrial fat
pad weight under the abdomen, and inhibited azoxymethane (AOM)/induced formation
of aberrant crypt foci (ACF) by 46%. Addition of pure beta/boswellic acid,
3/O/acetyl/beta/boswellic acid, 11/keto/beta/boswellic acid or
3/O/acetyl/11/keto/beta/boswellic acid to human leukemia HL/60 cell culture
inhibited DNA synthesis in HL/60 cells in a dose/dependent manner with IC50
values ranging from 0.6 to 7.1 microM. These results indicate that
beta/boswellic acid and its derivatives (the major constituents of Boswellin)
have anti/carcinogenic, anti/tumor, and anti/hyperlipidemic activities.
PMID: 11237186 [PubMed / indexed for MEDLINE]
49: Z Gastroenterol. 2001 Jan;39(1):11/7.
[Therapy of active Crohn disease with Boswellia serrata extract H 15]
[Article in German]
Gerhardt H, Seifert F, Buvari P, Vogelsang H, Repges R.
Colitis/Crohn/Ambulanz, I. Medizinische Klinik, Klinikum Mannheim der
Universitat Heidelberg.
BACKGROUND: The purpose of this clinical trial was to compare efficacy and
safety of the Boswellia serrata extract H15 with mesalazine for the treatment of
active Crohn's disease. PATIENTS AND METHODS: Randomised, double/blind,
verum/controlled, parallel group comparison for which 102 Patients were
randomised. The per protocol population included 44 patients treated with H15
and 39 patients treated with mesalazine. As primary outcome measure the change
of the Crohn Disease Activity Index (CDAI) between the status of enrolment and
end of therapy was chosen. H 15 was tested on non/inferiority compared to
standard treatment with mesalazine. RESULTS: The CDAI between the status of
enrolment and end of therapy after treatment with H15 was reduced by 90 and
after therapy with mesalazine by 53 scores in the mean. In this
non/inferiority/trial the test hypothesis was confirmed by the statistical
analysis. The difference between both treatments could not be proven to be
statistically significant in favor to H15 for the primary outcome measure. The
secondary efficacy endpoints confirm the assessment of the comparison of H15 and
mesalazine. The proven tolerability of H15 completes the results of the shown
clinical efficacy. CONCLUSIONS: The study confirms that therapy with H15 is not
inferior to mesalazine. This can be interpreted as evidence for the efficacy of
H15 according to the state of art in the treatment of active Crohn's disease
with Boswellia serrata extract, since the efficacy of mesalazine for this
indication has been approved by the health authorities. Considering both safety
and efficacy of Boswellia serrata extract H15 it appears to be superior over
mesalazine in terms of a benefit/risk/evaluation.
Publication Types:
Clinical Trial
Comparative Study
English Abstract
Randomized Controlled Trial
PMID: 11215357 [PubMed / indexed for MEDLINE]
50: Altern Med Rev. 2001 Feb;6(1):20/47.
The etiologies, pathophysiology, and alternative/complementary treatment of
asthma.
Miller AL.
Thorne Research, Inc, Dover, ID 83825, USA. alan@thorne.com
A chronic inflammatory disorder of the respiratory airways, asthma is
characterized by bronchial airway inflammation resulting in increased mucus
production and airway hyper/responsiveness. The resultant symptomatology
includes episodes of wheezing, coughing, and shortness of breath. Asthma is a
multifactorial disease process with genetic, allergic, environmental,
infectious, emotional, and nutritional components. The underlying
pathophysiology of asthma is airway inflammation. The underlying process driving
and maintaining the asthmatic inflammatory process appears to be an abnormal or
inadequately regulated CD4+ T/cell immune response. The T/helper 2 (Th2) subset
produces cytokines including interleukin/4 (IL/4), IL/5, IL/6, IL/9, IL/10, and
IL/13, which stimulate the growth, differentiation, and recruitment of mast
cells, basophils, eosinophils, and B/cells, all of which are involved in humoral
immunity, inflammation, and the allergic response. In asthma, this arm of the
immune response is overactive, while Th1 activity, generally corresponding more
to cell/mediated immunity, is dampened. It is not yet known why asthmatics have
this out/of/balance immune activity, but genetics, viruses, fungi, heavy metals,
nutrition, and pollution all can be contributors. A plant lipid preparation
containing sterols and sterolins has been shown to dampen Th2 activity.
Antioxidant nutrients, especially vitamins C and E, selenium, and zinc appear to
be necessary in asthma treatment. Vitamins B6 and B12 also may be helpful.
Omega/3 fatty acids from fish, the flavonoid quercetin, and botanicals Tylophora
asthmatica, Boswellia serrata and Petasites hybridus address the inflammatory
component. Physical modalities, including yoga, massage, biofeedback,
acupuncture, and chiropractic can also be of help.
Publication Types:
Review
PMID: 11207455 [PubMed / indexed for MEDLINE]
51: Eur J Med Res. 1998 Nov 17;3(11):511/4.
Effects of Boswellia serrata gum resin in patients with bronchial asthma:
results of a double/blind, placebo/controlled, 6/week clinical study.
Gupta I, Gupta V, Parihar A, Gupta S, Ludtke R, Safayhi H, Ammon HP.
Pharmakologie fur Naturwissenschaftler, Pharmazeutisches Institut der
Universitat Tubingen, Auf der Morgenstelle 8, D/72076 Tubingen, Germany.
The gum resin of Boswellia serrata, known in Indian Ayurvedic system of medicine
as Salai guggal, contains boswellic acids, which have been shown to inhibit
leukotriene biosynthesis. In a double/blind, placebo/controlled study forty
patients, 23 males and 17 females in the age range of 18 / 75 years having mean
duration of illness, bronchial asthma, of 9.58 +// 6.07 years were treated with
a preparation of gum resin of 300 mg thrice daily for a period of 6 weeks. 70%
of patients showed improvement of disease as evident by disappearance of
physical symptoms and signs such as dyspnoea, rhonchi, number of attacks,
increase in FEV subset1, FVC and PEFR as well as decrease in eosinophilic count
and ESR. In the control group of 40 patients 16 males and 24 females in the age
range of 14/58 years with mean of 32.95 +// 12.68 were treated with lactose 300
mg thrice daily for 6 weeks. Only 27% of patients in the control group showed
improvement. The data show a definite role of gum resin of Boswellia serrata in
the treatment of bronchial asthma.
Publication Types:
Clinical Trial
Randomized Controlled Trial
PMID: 9810030 [PubMed / indexed for MEDLINE]
52: Altern Med Rev. 1998 Aug;3(4):306/7.
Boswellia serrata.
[No authors listed]
PMID: 9734240 [PubMed / indexed for MEDLINE]
53: Arzneimittelforschung. 1998 Jun;48(6):668/74.
Effects of boswellic acids extracted from a herbal medicine on the biosynthesis
of leukotrienes and the course of experimental autoimmune encephalomyelitis.
Wildfeuer A, Neu IS, Safayhi H, Metzger G, Wehrmann M, Vogel U, Ammon HP.
Department of Pathology, Medical Faculty, University of Ulm, Germany.
Mixed acetylboswellic acids, pentacyclic triterpenes extracted from the gum
resin of Boswellia serrata Roxb., significantly inhibited the
ionophore/stimulated release of the leukotrienes (LT) B4 and C4 from intact
human polymorphonuclear neutrophil leukocytes (PMNLs), with IC50 values of 8.48
micrograms/ml and 8.43 micrograms/ml, respectively. Purified
acetyl/11/keto/beta/boswellic acid was about three times more potent as
inhibitor of the formation of both LTB4 (IC50 = 2.53 micrograms/ml) and LTC4
(IC50 = 2.26 micrograms/ml) from human PMNLs in the same assay. The comparative
agent MK 886 (3/[1/(4/chlorobenzyl)/3/t/butyl/thio/5/isopropylindol/2/yl]/
2,2/dimethylpropanoic acid, L/663,536, CAS 118, 414/82/7) was about 10 to
100/fold more active than the boswellic acids in inhibiting the formation of
5/lipoxygenase products in human PMNLs, with IC50 values of 0.0068 microgram/ml
(LTB4) and 0.49 microgram/ml (LTC4). After daily intraperitoneal dosage the
extract of mixed acetylboswellic acids (20 mg/kg) significantly reduced the
clinical symptoms in guinea pigs with experimental autoimmune encephalomyelitis
(EAE) between days 11 and 21. However, the inflammatory infiltrates in the brain
and the spinal cord were not significantly less extensive in the treated animals
than in the respective control group. The multiple intraperitoneal application
of boswellic acids did not inhibit the ionophore/challenged ex vivo release of
leukotrienes B4 and C4 from PMNLs separated from the blood of guinea pigs with
EAE. The boswellic acids have thus been characterized as selective, non/redox
and potent inhibitors of the biosynthesis of leukotrienes in vitro.
Publication Types:
In Vitro
PMID: 9689425 [PubMed / indexed for MEDLINE]
54: Planta Med. 1998 May;64(4):328/31.
Inhibitory activity of boswellic acids from Boswellia serrata against human
leukemia HL/60 cells in culture.
Shao Y, Ho CT, Chin CK, Badmaev V, Ma W, Huang MT.
Department of Plant Science, Cook College, Rutgers, State University of New
Jersey, New Brunswick, USA.
Four major triterpene acids including beta/boswellic acid (1),
3/O/acetyl/beta/boswellic acid (2), 11/keto/beta/boswellic acid (3), and
3/O/acetyl/11/keto/beta/boswellic acid (4) were isolated from the gum resin of
Boswellia serrata and examined for their in vitro antitumor activity. They
inhibited the synthesis of DNA, RNA and protein in human leukemia HL/60 cells in
a dose dependent manner with IC50 values ranging from 0.6 to 7.1 microM. Among
them, compound 4 induced the most pronounced inhibitory effects on DNA, RNA and
protein synthesis with IC50 values of 0.6, 0.5, and 4.1 microM, respectively.
The effect of 4 on DNA synthesis was found to be irreversible. Compound 4
significantly inhibited the cellular growth of HL/60 cells, but did not affect
cell viability.
PMID: 9619114 [PubMed / indexed for MEDLINE]
55: Z Rheumatol. 1998 Feb;57(1):11/6.
[Is H15 (resin extract of Boswellia serrata, "incense") a useful supplement to
established drug therapy of chronic polyarthritis? Results of a double/blind
pilot study]
[Article in German]
Sander O, Herborn G, Rau R.
Rheumatologische Klinik, Evangelisches Fachkrankenhaus Ratingen.
BACKGROUND: Leukotrienes and prostaglandines are important mediators of
inflammation. While prostaglandine synthesis can be influenced by NSAIDs
therapeutical approaches to the 5/lipoxygenase pathway are rare. Resinous
extracts of Boswellia serrata (H15, indish incense), known from traditional
ayurvedic medicine, decrease leukotriene synthesis in vitro. Case reports
suggest a clinical role for that drug. METHODS: Outpatients with active RA have
been enrolled into a multicenter controlled trial. Patients received 9 tablets
of active drug (3600 mg) or placebo daily in addition to their previous therapy.
Doses of NSAIDs could be adjusted on demand. Efficacy parameters, Ritchies Index
for swelling and pain, ESR, CRP, pain on VAS and NSAID dose were documented at
baseline and 6 and 12 weeks after initiation. Mean values and medians were
calculated to compare the groups for significant or clinically relevant change
from baseline or difference between both groups at any time point of
observation. RESULTS: A total of 78 patients were recruited in 4 centers, the
data have been published in abstract form. Only 37 patients (verum 18, placebo
19), enrolled in Ratingen were available for detailed efficacy and safety
analysis. All evaluations in these patients were performed by one investigator
(G.H.). There was no subjective, clinical or laboratory parameter showing a
significant or clinically relevant change from baseline or difference between
both groups at any time point of observation. The mean NSAID dose reduction
reached levels of 5.8% (H15) and 3.1% (placebo). One patient in each group
showed a good response in all parameters but 4 patients in each group worsened.
The others showed no alteration of their disease. CONCLUSION: Treatment with H15
showed no measurable efficacy. Controlled studies including a greater patient
population are necessary to confirm or reject our results.
Publication Types:
Clinical Trial
Comparative Study
Controlled Clinical Trial
English Abstract
Multicenter Study
Randomized Controlled Trial
PMID: 9566100 [PubMed / indexed for MEDLINE]
56: Eur J Med Res. 1997 Jan;2(1):37/43.
Effects of Boswellia serrata gum resin in patients with ulcerative colitis.
Gupta I, Parihar A, Malhotra P, Singh GB, Ludtke R, Safayhi H, Ammon HP.
Department of Medicine, Govt. Medical College, Jammu, J&K, India.
Ulcerative colitis is a chronic inflammatory disease of the colon where
leukotrienes are suggested to play an important role for keeping inflammation
active. Boswellic acids, the biologically active ingredients of the gum resin of
Boswellia serrata (Sallai guggal), have been shown to be specific, nonredox and
noncompetitive inhibitors of 5/lipoxygenase, the key enzyme of leukotriene
biosynthesis. In patients suffering from ulcerative colitis grade II and III the
effect of Boswellia serrata gum resin preparation (350 mg thrice daily for 6
weeks) on stool properties, histolopathology and scan microscopy of rectal
biopsies, blood parameters including Hb, serum iron, calcium, phosphorus,
proteins, total leukocytes and eosinophils was studied. Patients receiving
sulfasalazine (1 g thrice daily) served as controls. All parameters tested
improved after treatment with Boswellia serrata gum resin, the results being
similar compared to controls: 82% out of treated patients went into remission;
in case of sulfasalazine remission rate was 75%.
Publication Types:
Clinical Trial
Comparative Study
Controlled Clinical Trial
PMID: 9049593 [PubMed / indexed for MEDLINE]
57: Eur J Med Res. 1996 May 24;1(8):369/70.
Salai Guggal / Boswellia serrata: from a herbal medicine to a non/redox
inhibitor of leukotriene biosynthesis.
Ammon HP.
Publication Types:
Editorial
Review
PMID: 9360935 [PubMed / indexed for MEDLINE]
58: J Ethnopharmacol. 1993 Mar;38(2/3):113/9.
Mechanism of antiinflammatory actions of curcumine and boswellic acids.
Ammon HP, Safayhi H, Mack T, Sabieraj J.
Department of Pharmacology, Eberhard/Karls University, Tubingen, FRG.
Curcumine from Curcuma longa and the gum resin of Boswellia serrata, which were
demonstrated to act as anti/inflammatories in in vivo animal models, were
studied in a set of in vitro experiments in order to elucidate the mechanism of
their beneficial effects. Curcumine inhibited the 5/lipoxygenase activity in rat
peritoneal neutrophils as well as the 12/lipoxygenase and the cyclooxygenase
activities in human platelets. In a cell free peroxidation system curcumine
exerted strong antioxidative activity. Thus, its effects on the dioxygenases are
probably due to its reducing capacity. Boswellic acids were isolated from the
gum resin of Boswellia serrata and identified as the active principles.
Boswellic acids inhibited the leukotriene synthesis via 5/lipoxygenase, but did
not affect the 12/lipoxygenase and the cyclooxygenase activities. Additionally,
boswellic acids did not impair the peroxidation of arachidonic acid by iron and
ascorbate. The data suggest that boswellic acids are specific, non/redox
inhibitors of leukotriene synthesis either interacting directly with
5/lipoxygenase or blocking its translocation.
PMID: 8510458 [PubMed / indexed for MEDLINE]
59: Int J Immunopharmacol. 1992 Oct;14(7):1139/43.
Anticomplementary activity of boswellic acids//an inhibitor of C3/convertase of
the classical complement pathway.
Kapil A, Moza N.
Pharmacology Division, Regional Research Laboratory, Jammu Tawi, India.
Boswellic acids (BA), an anti/inflammatory and anti/arthritic principle/s of
Boswellia serrata, were found to possess anticomplementary activity. It inhibits
the in vitro immunohaemolysis of antibody/coated sheep erythrocytes by pooled
guinea/pig serum. The reduced immunohaemolysis was found to be due to inhibition
of C3/convertase of the classical complement pathway. The threshold
concentration for inhibiting C3/convertase was found to be 100 micrograms.
However, higher concentrations of BA showed constant inhibitory effects on
immunohaemolysis. BA also exhibited weak inhibitory effects on individual
components of the complement system. In vivo administration of BA also showed
the inhibitory effect on guinea/pig serum.
Publication Types:
In Vitro
PMID: 1452399 [PubMed / indexed for MEDLINE]
60: J Pharmacol Exp Ther. 1992 Jun;261(3):1143/6.
Boswellic acids: novel, specific, nonredox inhibitors of 5/lipoxygenase.
Safayhi H, Mack T, Sabieraj J, Anazodo MI, Subramanian LR, Ammon HP.
Department of Pharmacology, University of Tuebingen, FRG.
Isomers (alpha/ and beta/) of boswellic acids (BAs), 11/keto/beta/BA and their
acetyl derivatives were isolated from the gum resin of Boswellia serrata. BA and
derivatives concentration dependently decreased the formation of leukotriene B4
from endogenous arachidonic acid in rat peritoneal neutrophils. Among the BAs,
acetyl/11/keto/beta/BA induced the most pronounced inhibition of 5/lipoxygenase
(5/LO) product formation with an IC50 of 1.5 microM. In contrast to the redox
type 5/LO inhibitor nordihydroguaiaretic acid, BA in concentrations up to 400
microM did not impair the cyclooxygenase and 12/lipoxygenase in isolated human
platelets and the peroxidation of arachidonic acid by Fe/ascorbate. The data
strongly suggest that BAs are specific, nonreducing/type inhibitors of the 5/LO
product formation either interacting directly with the 5/LO or blocking its
translocation.
PMID: 1602379 [PubMed / indexed for MEDLINE]
61: Carbohydr Res. 1992 Jan;223:321/7.
Isolation and structure of a 4/O/methyl/glucuronoarabinogalactan from Boswellia
serrata.
Sen AK Sr, Das AK, Banerji N, Vignon MR.
Department of Organic Chemistry (Carbohydrate), Indian Institute of Chemical
Biology, Jadavpur, Calcutta.
PMID: 1596930 [PubMed / indexed for MEDLINE]
62: Planta Med. 1991 Jun;57(3):203/7.
Inhibition of leukotriene B4 formation in rat peritoneal neutrophils by an
ethanolic extract of the gum resin exudate of Boswellia serrata.
Ammon HP, Mack T, Singh GB, Safayhi H.
Department of Pharmacology, University of Tubingen, Federal Republic of Germany.
Suspensions of rat peritoneal polymorphonuclear leukocytes (PMNL) elicited with
glycogen were stimulated by calcium and ionophore to produce leukotrienes and
5/HETE from endogenous arachidonic acid (AA). We investigated the effect of
ethanolic extracts of the gum resin exudate of Boswellia serrata. A
concentration/dependent inhibition of LTB4 and 5/HETE production by different
charges of exudate extracts were found. All products of the 5/lipoxygenase
(5/LOx) from endogenous arachidonic acid (AA) in PMNL were reduced to the same
extent by the extracts tested. The ethanolic extract of the gum resin also
decreased 5/LOx mediated metabolisation of exogenously added AA to LTB4 and
5/HETE. Since steroidal/type anti/inflammatory drugs do not exert an immediate
effect in the test system used, we conclude that the activity of the 5/LOx
itself represents the side of inhibition by the gum resin extract. Therefore, an
inhibition of 5/LOx catalysed mediator synthesis might be involved in the
previously reported anti/inflammatory activity in vivo.
PMID: 1654575 [PubMed / indexed for MEDLINE]
63: J Ethnopharmacol. 1991 May/Jun;33(1/2):91/5.
Treatment of osteoarthritis with a herbomineral formulation: a double/blind,
placebo/controlled, cross/over study.
Kulkarni RR, Patki PS, Jog VP, Gandage SG, Patwardhan B.
Bryamjee Jeejeebhoy Medical College, University of Poona, Pune, India.
The clinical efficacy of a herbomineral formulation containing roots of Withania
somnifera, the stem of Boswellia serrata, rhizomes of Curcuma longa and a zinc
complex (Articulin/F), was evaluated in a randomized, double/blind, placebo
controlled, cross/over study in patients with osteoarthritis. After a one/month
single blind run/in period, 42 patients with osteoarthritis were randomly
allocated to receive either a drug treatment or a matching placebo for a period
of three months. After a 15/day wash/out period the patients were transferred to
the other treatment for a further period of three months. Clinical efficacy was
evaluated every fortnight on the basis of severity of pain, morning stiffness,
Ritchie articular index, joint score, disability score and grip strength. Other
parameters like erythrocyte sedimentation rate and radiological examination were
carried out on a monthly basis. Treatment with the herbomineral formulation
produced a significant drop in severity of pain (P less than 0.001) and
disability score (P less than 0.05). Radiological assessment, however, did not
show any significant changes in both the groups. Side effects observed with this
formulation did not necessitate withdrawal of treatment.
Publication Types:
Clinical Trial
Randomized Controlled Trial
PMID: 1943180 [PubMed / indexed for MEDLINE]
64: Biochem Pharmacol. 1989 Oct 15;38(20):3527/34.
Studies on the metabolism of glycosaminoglycans under the influence of new
herbal anti/inflammatory agents.
Reddy GK, Chandrakasan G, Dhar SC.
Department of Biochemistry, Central Leather Research Institute, Madras, India.
The in vivo effect of an herbal based, non/steroidal anti/inflammatory product,
salai guggal, prepared from the gum resin exudate of Boswellia serrata and its
active principle "boswellic acids" on glycosaminoglycan metabolism has been
studied in male albino rats. The biosynthesis of sulfated glycosaminoglycans, as
evaluated by the uptake of [35S]sulfate, and the content of glycosaminoglycans
were measured in specimens of skin, liver, kidney and spleen. Statistical
analysis of the data obtained with respect to the boswellic acids and salai
guggal were compared with those of ketoprofen. A significant reduction in
glycosaminoglycan biosynthesis was observed in rats treated with all of the
drugs. Glycosaminoglycan content was found to be decreased in the
ketoprofen/treated group, whereas that of the boswellic acids or salai guggal
treated groups remained unaltered. The catabolism of glycosaminoglycans was
followed by estimating the activities of lysosomal glycohydrolases, namely
beta/glucuronidase, beta/N/acetylglucosaminidase, cathepsin B1, cathepsin B2 and
cathepsin D, in tissues and by estimating the urinary excretion and hexosamine
and uronic acid. The degradation of glycosaminoglycans was found to be reduced
markedly in all drug/treated animals as compared to controls. The potential
significance of boswellic acids and salai guggal was discussed in the light of
changes in the metabolism of glycosaminoglycans.
Publication Types:
Comparative Study
Research Support, Non/U.S. Gov't
PMID: 2818645 [PubMed / indexed for MEDLINE]
65: Planta Med. 1971 Apr;19(4):333/41.
Analgesic and psychopharmacological effects of the gum resin of Boswellia
serrata.
Menon MK, Kar A.
Publication Types:
Comparative Study
PMID: 5573545 [PubMed / indexed for MEDLINE]
