Isorhamnetin and hyperoside derived from water dropwort inhibits inflammasome activation

Water dropwort (Oenanthe javanica), an umbelliferous plant, has been reported as hypolipidemic, antiplatelet, antitumor, or immune-stimulating agents and it has been suggested to cure cardiovascular disease and cancer. Present study aimed to evaluate the effect of the extracts of water dropwort (EWD) and its pharmacological molecules, hyperoside and isorhamnetin, on inflammatory response, especially inflammasome activation. The anti-inflammasome properties of EWD, isorhamnetin, and hyperoside were elucidated by human and mouse macrophages. EWD attenuated secretion of interleukin (IL)-1β and formation of Asc pyroptosome resulting from NLRP3, NLRC4, and AIM2 inflammasome activation without interruption of cytokine transcription. Isorhamnetin selectively inhibited NLRP3 and AIM2 inflammasome activation and down-regulated expression of pro-inflammatory cytokines. Hyperoside selectively interrupted NLRC4 and AIM2 inflammasome activation but did not alter cytokine expression. In addition, EWD, isorhamnetin, and hyperoside inhibited caspase-1. Isorhamnetin and hyperoside, a key molecule of water dropwort, have been suggested as candidates to attenuate inflammasome inhibition. [Display omitted]