Anti-hypertensive and composition as well as pharmacokinetics and tissues distribution of active ingredients from Alpinia zerumbet.

Alpinia zerumbet is a food flavor additive and a traditional medicine herb around the world. Several studies have reported that A. zerumbet has excellent effects on a variety of cardiovascular diseases, but its potential hypertensive applications, and pharmacokinetic features of main active substances have not been fully investigated. The mechanism of anti-hypertension with ethyl acetate extracts of A. zerumbet fruits (AZEAE) was evaluated by L -NNA-induced hypertensive rats and L -NAME-injured human umbilical vein endothelial cells (HUVECs). Blood pressure, echocardiographic cardiac index and H&E staining were used to preliminary evaluate the antihypertensive effect of AZEAE, the levels of TNF-α, IL-6, and IL-1β were evaluated by ELISA, and the proteins expression of IL-1β, IL-18, AGTR1, VCAM, iNOS, EDN1 and eNOS were also evaluated. In addition, isolation, identification, and activity screening of bioactive compounds were carried ou. Next, pharmacokinetics and tissues distribution of dihydro-5,6-dehydrokavain (DDK) in vivo were measured, and preliminary absorption mechanism was conducted with Caco-2 cell monolayers. AZEAE remarkably enhanced the state of hypertensive rats. Twelve compounds were isolated and identified, and five compounds were isolated from this plant for the first time. The isolated compounds also exhibited good resistance against injury of HUVECs. Moreover, pharmacokinetics and Caco-2 cell monolayers demonstrated AZEAE had better absorption capacity than DDK, and DDK exhibited differences in tissues distribution and gender difference. This study was the first to assess the potential hypertensive applications of A. zerumbet in vivo and vitro , and the first direct and concise study of the in vivo behavior of DDK and AZEAE. [Display omitted] • The effect and mechanism of AZEAE on hypertensive rats were measured for the first time. • Twelve bioactive substances were identified and were tested for anti-HUVECs injury. • The effect and mechanism of dihydro-5,6-dehydrokavain on HUVECs was measured for the first time. • The pharmacokinetics of monomer and DDK from AZEAE were studied for the first time. • The tissues distribution of DDK was evaluated for the first time. [ABSTRACT FROM AUTHOR]