Planta Med 2017; 83(12/13): 1020-1027
DOI: 10.1055/s-0043-107884
Biological and Pharmacological Activity
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Defined Structure-Activity Relationships of Boswellic Acids Determine Modulation of Ca2+ Mobilization and Aggregation of Human Platelets by Boswellia serrata Extracts[*]

Ulf Siemoneit1, **, Lars Tausch2, **, Daniel Poeckel1, Michael Paul3, Hinnak Northoff4, Andreas Koeberle1, 5, Johann Jauch3, Oliver Werz1, 5
  • 1Department of Pharmaceutical Analytics, Pharmaceutical Institute, Eberhard Karls University Tuebingen, Tuebingen, Germany
  • 2Institute of Pharmaceutical Chemistry, University of Frankfurt, Frankfurt, Germany
  • 3Institute of Organic Chemistry, University of Saarland, Saarbruecken, Germany
  • 4Institute for Clinical and Experimental Transfusion Medicine, University Medical Center Tuebingen, Tuebingen, Germany
  • 5Department of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, University of Jena, Jena, Germany
Further Information

Publication History

received 22 December 2016
revised 15 March 2017

accepted 25 March 2017

Publication Date:
12 April 2017 (eFirst)

Abstract

Boswellic acids constitute a group of unique pentacyclic triterpene acids from Boswellia serrata with 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+]i and 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 a B. serrata gum 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 A2 receptor 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+]i and aggregation of platelets (≥ 3 µM). 11-Keto-β-boswellic acid, the structural intermediate between 3-O-acetyl-11-keto-β-boswellic acid and β-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 of B. serrata gum extracts and prompts for careful evaluation of the safety of such extracts as herbal medicine in cardiovascular risk patients.

* Dedicated to Professor Dr. Max Wichtl in recognition of his outstanding contribution to pharmacognosy research.


** These two authors contributed equally to this work.


Supporting information