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

Boswellic acids constitute a group of unique pentacyclic triterpene acids from 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 Ca concentrations [Ca] 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 Ca mobilization and platelet aggregation depending on defined structural determinants with inductive effects predominating for a gum resin extract. 3--Acetyl-11-keto--boswellic acid potently suppressed Ca mobilization (IC = 6 µM) and aggregation (IC = 1 µM) when platelets were activated by collagen or the thromboxane A receptor agonist U-46619, but not upon thrombin. In contrast, -boswellic acid and 3--acetyl--boswellic acid, which lack the 11-keto moiety, were weak inhibitors of agonist-induced platelet responses, but instead they elicited elevation of [Ca] and aggregation of platelets (≥ 3 µM). 11-Keto--boswellic acid, the structural intermediate between 3--acetyl-11-keto--boswellic acid and -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 gum extracts and prompts for careful evaluation of the safety of such extracts as herbal medicine in cardiovascular risk patients.