title: Defined Structure-Activity Relationships of Boswellic Acids Determine Modulation of Ca2+ Mobilization and Aggregation of Human Platelets by Boswellia serrata Extracts.
abstract: Boswellic acids constitute a group of unique pentacyclic triterpene acids fromBoswellia serratawith multiple pharmacological activities that confer them anti-inflammatory and anti-tumoral properties. A subgroup of boswellic acids, characterized by an 11-keto group, elevates intracellular Ca2+concentrations [Ca2+]iand causes moderate aggregation of human platelets. How different BAs and their mixtures in pharmacological preparations affect these parameters in activated platelets has not been addressed, so far. Here, we show that boswellic acids either antagonize or induce Ca2+mobilization and platelet aggregation depending on defined structural determinants with inductive effects predominating for aB. serratagum resin extract. 3-O-Acetyl-11-keto-β-boswellic acid potently suppressed Ca2+mobilization (IC50= 6 µM) and aggregation (IC50= 1 µM) when platelets were activated by collagen or the thromboxane A2receptor agonist U-46619, but not upon thrombin. In contrast,β-boswellic acid and 3-O-acetyl-β-boswellic acid, which lack the 11-keto moiety, were weak inhibitors of agonist-induced platelet responses, but instead they elicited elevation of [Ca2+]iand aggregation of platelets (≥ 3 µM). 11-Keto-β-boswellic acid, the structural intermediate between 3-O-acetyl-11-keto-β-boswellic acid andβ-boswellic acid, was essentially inactive independent of the experimental conditions. Together, our study unravels the complex agonizing and antagonizing properties of boswellic acids on human platelets in pharmacologically relevant preparations ofB. serratagum extracts and prompts for careful evaluation of the safety of such extracts as herbal medicine in cardiovascular risk patients.
authors.affiliation: Department of Pharmaceutical Analytics, Pharmaceutical Institute, Eberhard Karls University Tuebingen, Tuebingen, Germany.
authors.forename: Ulf
authors.initials: U
authors.lastname: Siemoneit
authors.affiliation: Institute of Pharmaceutical Chemistry, University of Frankfurt, Frankfurt, Germany.
authors.forename: Lars
authors.initials: L
authors.lastname: Tausch
authors.affiliation: Department of Pharmaceutical Analytics, Pharmaceutical Institute, Eberhard Karls University Tuebingen, Tuebingen, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Poeckel
authors.affiliation: Institute of Organic Chemistry, University of Saarland, Saarbruecken, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Paul
authors.affiliation: Institute for Clinical and Experimental Transfusion Medicine, University Medical Center Tuebingen, Tuebingen, Germany.
authors.forename: Hinnak
authors.initials: H
authors.lastname: Northoff
authors.affiliation: Department of Pharmaceutical Analytics, Pharmaceutical Institute, Eberhard Karls University Tuebingen, Tuebingen, Germany.|Department of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, University of Jena, Jena, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Koeberle
authors.affiliation: Institute of Organic Chemistry, University of Saarland, Saarbruecken, Germany.
authors.forename: Johann
authors.initials: J
authors.lastname: Jauch
authors.affiliation: Department of Pharmaceutical Analytics, Pharmaceutical Institute, Eberhard Karls University Tuebingen, Tuebingen, Germany.|Department of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, University of Jena, Jena, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Werz
mesh_terms: D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects; D029743:Boswellia / Q000737:chemistry*; D002118:Calcium / Q000378:metabolism*; D006801:Humans; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014315:Triterpenes / Q000737:chemistry / Q000494:pharmacology*
chemical_list: C447943:11-keto-boswellic acid; C459792:3-O-acetyl-beta-boswellic acid; D000893:Anti-Inflammatory Agents; D010936:Plant Extracts; D014315:Triterpenes; C094432:acetyl-11-ketoboswellic acid; C054625:boswellic acid; D002118:Calcium