Adenostemmoic acid B suppresses NO production by downregulating the expression and inhibiting the enzymatic activity of iNOS

Abstract

Adenostemmoic acid B (AB) is a major compound found in Adenostemma lavenia ; it shows anti-melanogenic, anti-inflammatory, and cytotoxic activities. By modifying the 19th position (carboxy: involved in the avoidance of cytotoxicity) of AB, we succeed to separate these activities. Short-chain alkylation of the carboxy group enhanced anti-melanogenic activity, while long-chain alkylation (hydrophobic) resulted in the suppression of nitric oxide (NO) production and inducible NO synthase (iNOS) expression without anti-melanogenic activity. Re-modification of hydrophilic properties in these long-chain derivatives restored anti-melanogenic activity but did not suppress NO production. Unexpectedly, AB and derivatives with long chains linked by an anhydride bond were new iNOS inhibitors. These results suggest that AB modulates multiple physiological activities by regulating different targets, including iNOS. • Adenostemmoic acid B is a multipotential ingredient in Adenostemma lavenia. • Adenostemmoic acid B suppresses gene expression of tyrosinase (anti-melanogenesis) and iNOS (anti-inflammatory). • Adenostemmoic acid B and its derivatives with an anhydride bond inhibit iNOS enzyme activity.