8.1.1 Mechanisms of Inflammation

Erste Untersuchungen mit einem Extrakt aus salai guggal und Boswelliasäuren auf Entzündungsfaktoren aus der Acharidonsäurekaskade und andere Entzündungsfaktoren wurden am Lehrstuhl Pharmakologie des Pharmazeutischen Instituts der Universität Tübingen nach einem Treffen mit Dr. G.B. Sing aus Jammu (Indien) durchgeführt.










In vitro effects of an alcoholic extract from gum resin of Boswellia serrata AKBA/KBA on formation of 5-LOX products and elastase activity from polymorphnuclear leucozytes (PMNL)

aus: Ammon et al. 1991 und Safayhi et al. 1992






Hier noch einige der wichtigsten Ergebnisse unseres Instituts:















Recent Advances Regarding the Molecular Mechanisms of Triterpenic Acids: A Review (Part II).
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GR-mediated anti-inflammation of α-boswellic acid: Insights from in vitro and in silico studies.
Zhang J, Zhao J, Sun Y, Liang Y, Zhao J, Zou H, Zhang T, Ren L

Food Chem Toxicol. 2021 Sep;155():112379.
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Huoxuezhitong capsule ameliorates MIA-induced osteoarthritis of rats through suppressing PI3K/ Akt/ NF-κB pathway.
Ju L, Hu P, Chen P, Xue X, Li Z, He F, Qiu Z, Cheng J, Huang F

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An Anti-Inflammatory Composition of Resin Extracts Alleviates Pain and Protects Cartilage in Monoiodoacetate-Induced Osteoarthritis in Rats.
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Evid Based Complement Alternat Med. 2020;2020():7381625.
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Acetyl-α-boswellic acid and Acetyl-β-boswellic acid protects against caerulein-induced pancreatitis via down-regulating MAPKs in mice.
Zhang PY, Yu B, Men WJ, Bai RY, Chen MY, Wang ZX, Zeng T, Zhou K

Int Immunopharmacol. 2020 Sep;86():106682.
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A natural supplement formula reduces anti-oxidative stress and enhances osteo-chondrogenic differentiation potential in mesenchymal stem cells.
Kim DH, Kim DH, Heck BE, Shaffer M, Hur J, Yoo KH

J Clin Biochem Nutr. 2020 May;66(3):206-212.
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Structural and mechanistic insights into 5-lipoxygenase inhibition by natural products.
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Acetyl-11-keto-β-boswellic acid ameliorates cognitive deficits and reduces amyloid-β levels in APPswe/PS1dE9 mice through antioxidant and anti-inflammatory pathways.
Wei C, Fan J, Sun X, Yao J, Guo Y, Zhou B, Shang Y

Free Radic Biol Med. 2020 Apr;150():96-108.
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Anti-inflammatory and anti-cancer activities of frankincense: Targets, treatments and toxicities.
Efferth T, Oesch F

Semin Cancer Biol. 2022 May;80():39-57.
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Antioxidant, anti-inflammatory and anti-fibrotic effects of gum resin in CCl-induced hepatotoxicity.
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Exp Ther Med. 2020 Feb;19(2):1313-1321.
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Fractions of Suppress LTA, LTC, Cyclooxygenase-2 Activities and mRNA in HL-60 Cells and Reduce Lung Inflammation in BALB/c Mice.
Soni KK, Meshram D, Lawal TO, Patel U, Mahady GB

Curr Drug Discov Technol. 2021;18(1):95-104.
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Bolbolian S, Bozorgmehr MR, Morsali A

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The Effects of Frankincense Essential Oil on Stress in Rats.
Okano S, Honda Y, Kodama T, Kimura M

J Oleo Sci. 2019;68(10):1003-1009.
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Computational and Biological Comparisons of Plant Steroids as Modulators of Inflammation through Interacting with Glucocorticoid Receptor.
Morsy MA, Patel SS, El-Sheikh AAK, Savjani JK, Nair AB, Shah JN, Venugopala KN

Mediators Inflamm. 2019;2019():3041438.
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Screening for the anti-inflammation quality markers of Xiaojin Pills based on HPLC-MS/MS method, COX-2 inhibition test and protein interaction network.
Xiong X, He YN, Feng B, Pan Y, Zhang HZ, Ke XM, Zhang Y, Yang M, Han L, Zhang DK

Sci Rep. 2018 May;8(1):7454.
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A Placebo-Controlled Double-Blind Study Demonstrates the Clinical Efficacy of a Novel Herbal Formulation for Relieving Joint Discomfort in Human Subjects with Osteoarthritis of Knee.
Karlapudi V, Prasad Mungara AVV, Sengupta K, Davis BA, Raychaudhuri SP

J Med Food. 2018 May;21(5):511-520.
PMID: 29708818 [PubMed - indexed for MEDLINE]


Triterpene Acids from Frankincense and Semi-Synthetic Derivatives That Inhibit 5-Lipoxygenase and Cathepsin G.
Koeberle A, Henkel A, Verhoff M, Tausch L, König S, Fischer D, Kather N, Seitz S, Paul M, Jauch J, Werz O

Molecules. 2018 Feb;23(2):.
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Mbiantcha M, Ngouonpe Wembe A, Dawe A, Yousseu Nana W, Ateufack G

Evid Based Complement Alternat Med. 2017;2017():6374907.
PMID: 29362589 [PubMed - as supplied by publisher]


Methanolic extract of Boswellia serrata exhibits anti-cancer activities by targeting microsomal prostaglandin E synthase-1 in human colon cancer cells.
Ranjbarnejad T, Saidijam M, Moradkhani S, Najafi R

Prostaglandins Other Lipid Mediat. 2017 Jul;131():1-8.
PMID: 28549801 [PubMed - indexed for MEDLINE]


Antioxidant and Immune System Regulatory Properties of Extracts.
Beghelli D, Isani G, Roncada P, Andreani G, Bistoni O, Bertocchi M, Lupidi G, Alunno A

Oxid Med Cell Longev. 2017;2017():7468064.
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A Pilot Study to Examine the Effects of an Anti-inflammatory Supplement on Eicosanoid Derivatives in Patients with Chronic Kidney Disease.
Shelmadine BD, Bowden RG, Moreillon JJ, Cooke MB, Yang P, Deike E, Griggs JO, Wilson RL

J Altern Complement Med. 2017 Aug;23(8):632-638.
PMID: 28375641 [PubMed - indexed for MEDLINE]


Boswellia serrata resin extract alleviates azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced colon tumorigenesis.
Chou YC, Suh JH, Wang Y, Pahwa M, Badmaev V, Ho CT, Pan MH

Mol Nutr Food Res. 2017 Sep;61(9):.
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Synthesis of new analogs of AKBA and evaluation of their anti-inflammatory activities.
Meka B, Ravada SR, Murali Krishna Kumar M, Purna Nagasree K, Golakoti T

Bioorg Med Chem. 2017 Feb;25(4):1374-1388.
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Chemical composition and biological activities of extracts and essential oil of Boswellia dalzielii leaves.
Kohoude MJ, Gbaguidi F, Agbani P, Ayedoun MA, Cazaux S, Bouajila J

Pharm Biol. 2017 Dec;55(1):33-42.
PMID: 27650786 [PubMed - indexed for MEDLINE]


Chemical composition, antiproliferative, antioxidant and antibacterial activities of essential oils from aromatic plants growing in Sudan.
Yagi S, Babiker R, Tzanova T, Schohn H

Asian Pac J Trop Med. 2016 Aug;9(8):763-70.
PMID: 27569885 [PubMed - as supplied by publisher]


Antioxidant effects of hydroxysafflor yellow A and acetyl-11-keto-β-boswellic acid in combination on isoproterenol-induced myocardial injury in rats.
Chen M, Wang M, Yang Q, Wang M, Wang Z, Zhu Y, Zhang Y, Wang C, Jia Y, Li Y, Wen A

Int J Mol Med. 2016 Jun;37(6):1501-10.
PMID: 27121241 [PubMed - indexed for MEDLINE]


α-Pinene, linalool, and 1-octanol contribute to the topical anti-inflammatory and analgesic activities of frankincense by inhibiting COX-2.
Li XJ, Yang YJ, Li YS, Zhang WK, Tang HB

J Ethnopharmacol. 2016 Feb;179():22-6.
PMID: 26721216 [PubMed - indexed for MEDLINE]


Enhanced Neuroprotection of Acetyl-11-Keto-β-Boswellic Acid (AKBA)-Loaded O-Carboxymethyl Chitosan Nanoparticles Through Antioxidant and Anti-Inflammatory Pathways.
Ding Y, Qiao Y, Wang M, Zhang H, Li L, Zhang Y, Ge J, Song Y, Li Y, Wen A

Mol Neurobiol. 2016 Aug;53(6):3842-3853.
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Synthesis and biological evaluation of boswellic acid-NSAID hybrid molecules as anti-inflammatory and anti-arthritic agents.
Shenvi S, Kiran KR, Kumar K, Diwakar L, Reddy GC

Eur J Med Chem. 2015 Jun;98():170-8.
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Antioxidant and hepatoprotective effects of Boswellia ovalifoliolata bark extracts.
Mahesh BU, Shrivastava S, Pragada RR, Naidu VG, Sistla R

Chin J Nat Med. 2014 Sep;12(9):663-71.
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Cardioprotective and antioxidant effects of oleogum resin "Olibanum" from Bos Boswellia carteri Birdw. (Bursearceae).
Zaki AA, Hashish NE, Amer MA, Lahloub MF

Chin J Nat Med. 2014 May;12(5):345-50.
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Tetra- and pentacyclic triterpene acids from the ancient anti-inflammatory remedy frankincense as inhibitors of microsomal prostaglandin E(2) synthase-1.
Verhoff M, Seitz S, Paul M, Noha SM, Jauch J, Schuster D, Werz O

J Nat Prod. 2014 Jun;77(6):1445-51.
PMID: 24844534 [PubMed - indexed for MEDLINE]


Boswellia serrata extract attenuates inflammatory mediators and oxidative stress in collagen induced arthritis.
Umar S, Umar K, Sarwar AH, Khan A, Ahmad N, Ahmad S, Katiyar CK, Husain SA, Khan HA

Phytomedicine. 2014 May;21(6):847-56.
PMID: 24667331 [PubMed - indexed for MEDLINE]


Boswellia serrata has beneficial anti-inflammatory and antioxidant properties in a model of experimental colitis.
Hartmann RM, Fillmann HS, Martins MI, Meurer L, Marroni NP

Phytother Res. 2014 Sep;28(9):1392-8.
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Major constituents of Boswellia carteri resin exhibit cyclooxygenase enzyme inhibition and antiproliferative activity.
Ali SI, Zhang CR, Mohamed AA, El-Baz FK, Hegazy AK, Kord MA, Nair MG

Nat Prod Commun. 2013 Oct;8(10):1365-6.
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The selective 5-LOX inhibitor 11-keto-β-boswellic acid protects against myocardial ischemia reperfusion injury in rats: involvement of redox and inflammatory cascades.
Elshazly SM, Abd El Motteleb DM, Nassar NN

Naunyn Schmiedebergs Arch Pharmacol. 2013 Sep;386(9):823-33.
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The Antioxidant Capacity and Anti-diabetic Effect of Boswellia serrata Triana and Planch Aqueous Extract in Fertile Female Diabetic Rats and the Possible Effects on Reproduction and Histological Changes in the Liver and Kidneys.
Azemi ME, Namjoyan F, Khodayar MJ, Ahmadpour F, Darvish Padok A, Panahi M

Jundishapur J Nat Pharm Prod. 2012;7(4):168-75.
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A novel C(28)-hydroxylated lupeolic acid suppresses the biosynthesis of eicosanoids through inhibition of cytosolic phospholipase A(2).
Verhoff M, Seitz S, Northoff H, Jauch J, Schaible AM, Werz O

Biochem Pharmacol. 2012 Sep;84(5):681-91.
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Evaluation of the anti-inflammatory and analgesic properties of individual and combined extracts from Commiphora myrrha, and Boswellia carterii.
Su S, Hua Y, Wang Y, Gu W, Zhou W, Duan JA, Jiang H, Chen T, Tang Y

J Ethnopharmacol. 2012 Jan;139(2):649-56.
PMID: 22178177 [PubMed - indexed for MEDLINE]


Boswellic acids from frankincense inhibit lipopolysaccharide functionality through direct molecular interference.
Henkel A, Kather N, Mönch B, Northoff H, Jauch J, Werz O

Biochem Pharmacol. 2012 Jan;83(1):115-21.
PMID: 22001311 [PubMed - indexed for MEDLINE]


Anti-inflammatory, antinociceptive and antioxidant activities of the endemic Soqotraen Boswellia elongata Balf. f. and Jatropha unicostata Balf. f. in different experimental models.
Mothana RA

Food Chem Toxicol. 2011 Oct;49(10):2594-9.
PMID: 21777643 [PubMed - indexed for MEDLINE]


Growth inhibitory, apoptotic and anti-inflammatory activities displayed by a novel modified triterpenoid, cyano enone of methyl boswellates.
Ravanan P, Singh SK, Rao GS, Kondaiah P

J Biosci. 2011 Jun;36(2):297-307.
PMID: 21654084 [PubMed - indexed for MEDLINE]


Inhibition of microsomal prostaglandin E2 synthase-1 as a molecular basis for the anti-inflammatory actions of boswellic acids from frankincense.
Siemoneit U, Koeberle A, Rossi A, Dehm F, Verhoff M, Reckel S, Maier TJ, Jauch J, Northoff H, Bernhard F, Doetsch V, Sautebin L, Werz O

Br J Pharmacol. 2011 Jan;162(1):147-62.
PMID: 20840544 [PubMed - indexed for MEDLINE]


Discovery of cyclooxygenase inhibitors from medicinal plants used to treat inflammation.
Cao H, Yu R, Choi Y, Ma ZZ, Zhang H, Xiang W, Lee DY, Berman BM, Moudgil KD, Fong HH, van Breemen RB

Pharmacol Res. 2010 Jun;61(6):519-24.
PMID: 20188172 [PubMed - indexed for MEDLINE]


Comparative study of the chemical composition and antioxidant activity of six essential oils and their components.
Yang SA, Jeon SK, Lee EJ, Shim CH, Lee IS

Nat Prod Res. 2010;24(2):140-51.
PMID: 20077307 [PubMed - indexed for MEDLINE]


Boswellia frereana (frankincense) suppresses cytokine-induced matrix metalloproteinase expression and production of pro-inflammatory molecules in articular cartilage.
Blain EJ, Ali AY, Duance VC

Phytother Res. 2010 Jun;24(6):905-12.
PMID: 19943332 [PubMed - indexed for MEDLINE]


Identification of human cathepsin G as a functional target of boswellic acids from the anti-inflammatory remedy frankincense.
Tausch L, Henkel A, Siemoneit U, Poeckel D, Kather N, Franke L, Hofmann B, Schneider G, Angioni C, Geisslinger G, Skarke C, Holtmeier W, Beckhaus T, Karas M, Jauch J, Werz O

J Immunol. 2009 Sep;183(5):3433-42.
PMID: 19648270 [PubMed - indexed for MEDLINE]


On the interference of boswellic acids with 5-lipoxygenase: mechanistic studies in vitro and pharmacological relevance.
Siemoneit U, Pergola C, Jazzar B, Northoff H, Skarke C, Jauch J, Werz O

Eur J Pharmacol. 2009 Mar;606(1-3):246-54.
PMID: 19374837 [PubMed - indexed for MEDLINE]


Studies of the in vitro anticancer, antimicrobial and antioxidant potentials of selected Yemeni medicinal plants from the island Soqotra.
Mothana RA, Lindequist U, Gruenert R, Bednarski PJ

BMC Complement Altern Med. 2009 Mar;9():7.
PMID: 19320966 [PubMed - indexed for MEDLINE]


Antiinflammatory and antiatherogenic effects of the NF-kappaB inhibitor acetyl-11-keto-beta-boswellic acid in LPS-challenged ApoE-/- mice.
Cuaz-Pérolin C, Billiet L, Baugé E, Copin C, Scott-Algara D, Genze F, Büchele B, Syrovets T, Simmet T, Rouis M

Arterioscler Thromb Vasc Biol. 2008 Feb;28(2):272-7.
PMID: 18032778 [PubMed - indexed for MEDLINE]


Identification and functional analysis of cyclooxygenase-1 as a molecular target of boswellic acids.
Siemoneit U, Hofmann B, Kather N, Lamkemeyer T, Madlung J, Franke L, Schneider G, Jauch J, Poeckel D, Werz O

Biochem Pharmacol. 2008 Jan;75(2):503-13.
PMID: 17945191 [PubMed - indexed for MEDLINE]


Boswellic acids and glucosamine show synergistic effect in preclinical anti-inflammatory study in rats.
Singh S, Khajuria A, Taneja SC, Khajuria RK, Singh J, Qazi GN

Bioorg Med Chem Lett. 2007 Jul;17(13):3706-11.
PMID: 17481895 [PubMed - indexed for MEDLINE]


Boswellic acids stimulate arachidonic acid release and 12-lipoxygenase activity in human platelets independent of Ca2+ and differentially interact with platelet-type 12-lipoxygenase.
Poeckel D, Tausch L, Kather N, Jauch J, Werz O

Mol Pharmacol. 2006 Sep;70(3):1071-8.
PMID: 16788089 [PubMed - indexed for MEDLINE]


Anti-inflammatory activities of the triterpene acids from the resin of Boswellia carteri.
Banno N, Akihisa T, Yasukawa K, Tokuda H, Tabata K, Nakamura Y, Nishimura R, Kimura Y, Suzuki T

J Ethnopharmacol. 2006 Sep;107(2):249-53.
PMID: 16621377 [PubMed - indexed for MEDLINE]


3-O-acetyl-11-keto-boswellic acid decreases basal intracellular Ca2+ levels and inhibits agonist-induced Ca2+ mobilization and mitogen-activated protein kinase activation in human monocytic cells.
Poeckel D, Tausch L, George S, Jauch J, Werz O

J Pharmacol Exp Ther. 2006 Jan;316(1):224-32.
PMID: 16174802 [PubMed - indexed for MEDLINE]


Induction of central signalling pathways and select functional effects in human platelets by beta-boswellic acid.
Poeckel D, Tausch L, Altmann A, Feisst C, Klinkhardt U, Graff J, Harder S, Werz O

Br J Pharmacol. 2005 Oct;146(4):514-24.
PMID: 16086030 [PubMed - indexed for MEDLINE]


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

Indian J Exp Biol. 2005 Jun;43(6):509-16.
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Effects of an acetone extract of Boswellia carterii Birdw. (Burseraceae) gum resin on adjuvant-induced arthritis in lewis rats.
Fan AY, Lao L, Zhang RX, Zhou AN, Wang LB, Moudgil KD, Lee DY, Ma ZZ, Zhang WY, Berman BM

J Ethnopharmacol. 2005 Oct;101(1-3):104-9.
PMID: 15970410 [PubMed - indexed for MEDLINE]


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

Br J Pharmacol. 2004 Jan;141(2):223-32.
PMID: 14691050 [PubMed - indexed for MEDLINE]


Phosphorylation- and stimulus-dependent inhibition of cellular 5-lipoxygenase activity by nonredox-type inhibitors.
Fischer L, Szellas D, Rådmark O, Steinhilber D, Werz O

FASEB J. 2003 May;17(8):949-51.
PMID: 12670876 [PubMed - indexed for MEDLINE]


Boswellic acids activate p42(MAPK) and p38 MAPK and stimulate Ca(2+) mobilization.
Altmann A, Fischer L, Schubert-Zsilavecz M, Steinhilber D, Werz O

Biochem Biophys Res Commun. 2002 Jan;290(1):185-90.
PMID: 11779151 [PubMed - indexed for MEDLINE]


Stimulation of leukotriene synthesis in intact polymorphonuclear cells by the 5-lipoxygenase inhibitor 3-oxo-tirucallic acid.
Boden SE, Schweizer S, Bertsche T, Düfer M, Drews G, Safayhi H

Mol Pharmacol. 2001 Aug;60(2):267-73.
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Workup-dependent formation of 5-lipoxygenase inhibitory boswellic acid analogues.
Schweizer S, von Brocke AF, Boden SE, Bayer E, Ammon HP, Safayhi H

J Nat Prod. 2000 Aug;63(8):1058-61.
PMID: 10978197 [PubMed - indexed for MEDLINE]


Concentration-dependent potentiating and inhibitory effects of Boswellia extracts on 5-lipoxygenase product formation in stimulated PMNL.
Safayhi H, Boden SE, Schweizer S, Ammon HP

Planta Med. 2000 Mar;66(2):110-3.
PMID: 10763581 [PubMed - indexed for MEDLINE]


Characterization of an acetyl-11-keto-beta-boswellic acid and arachidonate-binding regulatory site of 5-lipoxygenase using photoaffinity labeling.
Sailer ER, Schweizer S, Boden SE, Ammon HP, Safayhi H

Eur J Biochem. 1998 Sep;256(2):364-8.
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Nonredox 5-lipoxygenase inhibitors require glutathione peroxidase for efficient inhibition of 5-lipoxygenase activity.
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Mol Pharmacol. 1998 Aug;54(2):445-51.
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Inhibition by boswellic acids of human leukocyte elastase.
Safayhi H, Rall B, Sailer ER, Ammon HP

J Pharmacol Exp Ther. 1997 Apr;281(1):460-3.
PMID: 9103531 [PubMed - indexed for MEDLINE]


Structure-activity relationships of the nonredox-type non-competitive leukotriene biosynthesis inhibitor acetyl-11-keto-β-boswellic acid.
Sailer ER, Hoernlein RF, Ammon HP, Safayhi H

Phytomedicine. 1996 May;3(1):73-4.
PMID: 23194865 [PubMed - as supplied by publisher]


5-Lipoxygenase inhibition by acetyl-11-keto-β-boswellic acid (AKBA) by a novel mechanism.
Safayhi H, Sailer ER, Ammon HP

Phytomedicine. 1996 May;3(1):71-2.
PMID: 23194864 [PubMed - as supplied by publisher]


Acetyl-11-keto-beta-boswellic acid (AKBA): structure requirements for binding and 5-lipoxygenase inhibitory activity.
Sailer ER, Subramanian LR, Rall B, Hoernlein RF, Ammon HP, Safayhi H

Br J Pharmacol. 1996 Feb;117(4):615-8.
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Mechanism of 5-lipoxygenase inhibition by acetyl-11-keto-beta-boswellic acid.
Safayhi H, Sailer ER, Ammon HP

Mol Pharmacol. 1995 Jun;47(6):1212-6.
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Mechanism of antiinflammatory actions of curcumine and boswellic acids.
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J Ethnopharmacol. 1993 Mar;38(2-3):113-9.
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Anti-inflammatory activity of resins from some species of the plant family Burseraceae.
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Planta Med. 1993 Feb;59(1):12-6.
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A sensitive and relevant model for evaluating anti-inflammatory activity-papaya latex-induced rat paw inflammation.
Gupta OP, Sharma N, Chand D

J Pharmacol Toxicol Methods. 1992 Aug;28(1):15-9.
PMID: 1392054 [PubMed - indexed for MEDLINE]


Boswellic acids: novel, specific, nonredox inhibitors of 5-lipoxygenase.
Safayhi H, Mack T, Sabieraj J, Anazodo MI, Subramanian LR, Ammon HP

J Pharmacol Exp Ther. 1992 Jun;261(3):1143-6.
PMID: 1602379 [PubMed - indexed for MEDLINE]


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

Planta Med. 1991 Jun;57(3):203-7.
PMID: 1654575 [PubMed - indexed for MEDLINE]


Pharmacology of an extract of salai guggal ex-Boswellia serrata, a new non-steroidal anti-inflammatory agent.
Singh GB, Atal CK

Agents Actions. 1986 Jun;18(3-4):407-12.
PMID: 3751752 [PubMed - indexed for MEDLINE]