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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 Siemoneit   **
1   Department of Pharmaceutical Analytics, Pharmaceutical Institute, Eberhard Karls University Tuebingen, Tuebingen, Germany
,
Lars Tausch   **
2   Institute of Pharmaceutical Chemistry, University of Frankfurt, Frankfurt, Germany
,
Daniel Poeckel
1   Department of Pharmaceutical Analytics, Pharmaceutical Institute, Eberhard Karls University Tuebingen, Tuebingen, Germany
,
Michael Paul
3   Institute of Organic Chemistry, University of Saarland, Saarbruecken, Germany
,
Hinnak Northoff
4   Institute for Clinical and Experimental Transfusion Medicine, University Medical Center Tuebingen, Tuebingen, Germany
,
Andreas Koeberle
1   Department of Pharmaceutical Analytics, Pharmaceutical Institute, Eberhard Karls University Tuebingen, Tuebingen, Germany
5   Department of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, University of Jena, Jena, Germany
,
Johann Jauch
3   Institute of Organic Chemistry, University of Saarland, Saarbruecken, Germany
,
Oliver Werz
1   Department of Pharmaceutical Analytics, Pharmaceutical Institute, Eberhard Karls University Tuebingen, Tuebingen, Germany
5   Department of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, University of Jena, Jena, Germany
› Author Affiliations
Further Information

Publication History

received 22 December 2016
revised 15 March 2017

accepted 25 March 2017

Publication Date:
12 April 2017 (online)

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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.

Key words

Boswellia serrata - Burseraceae - boswellic acids - platelets - calcium - collagen - aggregation

* 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

    Preparation of B. serrata extracts, neutral and acidic fractions, and HPLC analysis thereof as well as quantification of BAs are available as Supporting Information.

  • Supporting Information
 

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