pharmacological profile of boswellic acids obtained from boswellia serrata as a new type of...
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but are at least available as dietary supplement.We summarized published clinical trials that hadbeen performed with respect to the treatment of
various chronic inflammatory diseases includingarthritis, colitis, Crohn’s Disease, asthma as well as ofcancer.
doi:10.1016/j.phymed.2008.03.011
Development steps of the herbal medicinal product
Boswelanr
for maintaining remission of Crohn’s disease
J.A. Schwarza, W.H. Holtmeierb, C. Skarkec
aConsultant 63303 Dreieich, Germany
bChefarzt der Medizinischen Klinik, Krankenhaus Porz a.R.,
51149 Koln, GermanycKlinisches Studienzentrum Rhein-Main/ZAFES, Univ.
Frankfurt, D-60528 Frankfurt am Main, Germany
(Currently at: Alexander von Humboldt-Fellow, Institute for
Translational Medicine and Therapeutics (ITMAT), Depart-
ment of Pharmacology, University Pennsylvania, Philadelphia,
PA 19104, USA).
E-mail address: [email protected]
Boswellia serrata gum resin was formulated into softgelatine capsules as semifluid mass from its ethanolextract mixed with a polyethylene as inert carrier. Thescientific advice by the competent Higher FederalAuthority in Germany (BfArM) triggered two clinicaltrials: The Phase II trial ‘‘A multicenter, randomized,double-blind, placebo-controlled study of an orally
administered Boswellia serrata Extract PS0201Bo formaintaining remission of Crohn’s Disease’’ (Co-ordinat-
ing Investigator: PD Dr. med. Wolfgang Holtmeier,
Vorlage-Nr.: 4021191) was started in 6 investigationalsites in Germany but was soon increased to 25 sites dueto poor patient recruitment. The Phase I trial addressedthe ‘‘Safety, tolerability and pharmacokinetics of asingle dose application of two Boswellia serrata extractcapsules in healthy male volunteers. Part I: Doubleblind, randomized, placebo controlled, sensory cross-over discrimination test, Part II: Open, randomized,cross-over pharmacokinetics (11-keto-b-boswellicacid – KBA and acetyl-11-keto-b-boswellic acid –AKBA) after fasting or an standardized light break-fast’’ (Principal Investigator: Dr. med. Carsten
Skarke, EudraCT No: 2006-002939-24, Vorlage-Nr.:
4031905). The regulatory requirements and hurdlesas well as the present status of the Crohn’s Diseasetrial and the results of the Phase I trial will bepresented.
doi:10.1016/j.phymed.2008.03.010
Pharmacological profile of boswellic acids obtained from
Boswellia serrata as a new type of non-steroidal anti-in-
flammatory drug
G.B. SinghRegional Research Laboratory Jammu, Jammu, India
(Present address: Indian Institute of Integrative Medicine,
India).
E-mail address: [email protected]
Over last three decades, we have been activelyengaged in research and development of safe andeffective anti-inflammatory drugs particularly fromnatural sources (Singh et al., 1986, 1993, 1994a, b,1996a–c) with selective inhibitory action on LTB4.Based on our research work alcoholic extract of salaiguggal ex-Boswellia serrata was marketed in India in1982 as SALLAKI with no reports of adverse effects(H-15 in Switzerland). Further study on this resulted inisolation of boswellic acids. Anti-inflammatory activity(AIA) of boswellic acids (BA) was evaluated in a varietyof test models. BA in a dose range of 50–200mg/kgorally showed statistically significant dose-related in-hibitory action. In acute tests of carrageenan, histamineand dextran-induced edema, BA produced 26–48%inhibitory action. It showed 42–60% inhibitory effectin acetic acid-induced vascular permeability in mice. In
chronic test of formaldehyde, developing and estab-lished adjuvant polyarthritis, BA elicited anti-arthriticaction by 32–62% and decreased secondary lesions. Insodium urate gouty arthritis in dogs and bovine serumalbumin (BSA) arthritis in rabbits, BA demonstratedinhibitory action of the knee joints swelling andleucocytes count of aspirated synovial fluid (21–58%).In carragenan- and dextran-induced pleurisy in rats, BAdecreased the exudate volume and migration of luco-cytes. It showed weak anti-pyretic action in pyretic ratsand rabbits but no analgesic effect. It failed to show anyulcerogenic potential. On biochemical investigations,BA decreased the arthritis elevated levels of SGOT &SGPT and alkaline phosphatase levels. It failed toexhibit cytotoxic action on PMNL as revealed by thedye exclusion test or irritant effect on rabbit cornea.Unlike other NSAID’s orally administered, BA failed toprolong gestation period, parturition time in pregnantrats and did not affect the of castor oil-induced diarrheaeffects attributed to inhibition of PG’s. BA inhibited theformation LTB4 from endogenous arachidonic acid inrat peritoneal neutrophils (Ammon et al., 1991; Safahyiet al., 1992).
In acute toxicity, BA (2 g/Kg) produced nomortality in rats and mice over 72 h. In subacute toxicity
ARTICLE IN PRESSAbstracts / Phytomedicine 15 (2008) 541–546544
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(4 weeks) and chronic toxicity (6 months) in ratsand monkeys, BA produced no undesirable effects.Clinical, haematological and biochemical para-meters were found to be within the limits andhistopathology showed no changes in cell structure.Clinical studies carried on 60 volunteers patients ofarthritis over 8 weeks revealed no untoward symptoms.Hence, BA is a new class of anti-inflammatory and anti-arthritic drug with a novel mode of inhibitory action onLTB4.
References
Ammon, et al., 1991. Planta Med, 57203–57208.
Safahyi, H., et al., 1992. J. Pharm. Exp; Ther. 261, 1143–1146.
Singh, G.B., et al., 1986. Agents Actions 18 (3–4), 407–412.
Singh, G.B., et al., 1993. Drugs Future 18 (4), 307–309.
Singh, G.B., et al., 1994a. Drugs Future 19 (6), 549–551.
Singh, G.B., et al., 1994b. Drugs Future 19, 450–451.
Singh, G.B., et al., 1996a. Drugs Today 32 (2), 109–112.
Singh, G.B., et al., 1996b. Phytomedicine 3 (1), 81–85.
Singh, G.B., et al., 1996c. Phytomedicine 3 (1), 87–90.
doi:10.1016/j.phymed.2008.03.009
Systemic availability of boswellic acids following oral
administration
M. Abdel Tawaba, P. Krugera, M. Schubert-Zsilavecza,b
aCentral Laboratory of German Pharmacists, 65760 Eschborn,
GermanybInstitute of Pharmaceutical Chemistry, University of Frankfurt,
60438 Frankfurt, Germany
E-mail address: [email protected]
In vitro studies revealed, that boswellic acids (BAs),the active ingredients of Boswellia serrata extract, mayrepresent promising alternative/adjuvant agents for thetreatment of inflammatory diseases and cerebral oede-ma. 11-Keto-b-boswellic acid (KBA) and 3-acetyl-11-keto-b-boswellic acid (AKBA) are the most potentinhibitors of 5-lipoxygenase with IC50 values of 2.8and 1.5 mM, respectively, in intact rat polymorpho-nuclear leucocytes (PMNLs) (Sailer et al., 1996). In theframe of a preliminary pharmacokinetic study theconcentration of KBA was determined to be 1.6 mM inhuman plasma following single-dose administration of1600mg B. serrata extract, whereas AKBA could not bedetected (Tawab et al., 2001).
In rats, dosed with 240mg/kg B. serrata extract, KBAand AKBA were determined in plasma at 0.4 and0.2 mM, respectively, and at 0.3 mM in brain. The ratbrain-to-plasma ratios were 0.5 for KBA and 0.8 forAKBA, indicating a higher brain penetration of AKBA(Reising et al., 2005).
Studies on the metabolic stability of KBA and AKBArevealed that KBA undergoes an extensive phase Imetabolism yielding hydroxylated derivatives. AKBA ismetabolically stable and is not deacetylated to KBA.Permeability studies using CaCo-2 cells suggest poorabsorption of KBA and AKBA from the gastrointest-inal tract. Any attempts to enhance the bioavailability ofBAs should focus on the metabolically more stableAKBA (Kruger et al., 2008).
ReferencesKruger, P., et al., 2008. Drug Metab. Disp., 36(6).
Reising, K., et al., 2005. Anal. Chem. 77 (20), 6640–6645.
Sailer, E.R., et al., 1996. Br. J. Pharmacol. 117 (4), 615–618.
Tawab, M., et al., 2001. J. Chromatogr. Biomed. Appl. 761 (2),
221–227.
doi:10.1016/j.phymed.2008.03.013
Boswellia and the complement system: A multiherbal
drug for multitarget therapy
H. Wagnera, U. Knausb
aDepartment of Pharmacy, Center of Pharma Research, Univer-
sity of Munich, Butenandtstrasse 5-13, 81377 Munich, GermanybDepartment of Immunology, The Scripps Research Institute,
10666 North Pines Road, La Jolla, CA 92037, USA
E-mail address: [email protected]
Because a pathologically prolonged and sustainedactivation of the complement system is implicated in avariety of inflammatory disorders, from rheumatoidarthritis and glomerulonephritis to systemic lupuserythematodes, we have investigated the influence ofb-boswellic acid from Boswellia carteri on the classical
and alternative complement pathways. Significant re-duction of immunohemolysis in vitro was observed atb-boswellic acid concentrations between 0.05 and0.1mM with an IC50 value of about 10mM (Knaus andWagner, 1996). All other pharmacological activitiesreported for the Boswellia extract, the b-boswellic acid,the four other boswellic acid derivatives and the essentialoil of the resin, allow us to suggest that Boswellia can beconsidered a promising example of a multiherbal drugfor multitarget synergy therapy (Wagner, 2006).
ReferencesKnaus, U., Wagner, H., 1996. Phytomedicine 3 (1), 77–81.
Wagner, H., 2006. Phytomedicine 13, 122–129.
doi:10.1016/j.phymed.2008.03.014
ARTICLE IN PRESSAbstracts / Phytomedicine 15 (2008) 541–546 545