Tetrastigma hemsleyanum alleviates sarcoidosis through metabolomic regulation and Th17/Treg immune homeostasis

Abstract

• β-sitosterol, oleanolic acid and procyanidin B1 were significantly different components in aqueous and ethanol extract of T. hemsleyanum. • T. hemsleyanum suppressed inflammatory response and maintained the Treg/Th17 immune homeostasis in sarcoidosis mice. • T. hemsleyanum relieved the metabolic disorder in sarcoidosis mice. This study investigated the protective effects and mechanism of Tetrastigma hemsleyanum ( T. hemsleyanum ) in sarcoidosis mice. Through the integrated analysis of network pharmacology, molecular docking and HPLC, oleanolic acid, procyanidin B1 and β-sitosterol were considered to be the major components of T. hemsleyanum against sarcoidosis. T. hemsleyanum remarkably attenuated the increase of IL-6 and IL-17A, the percentage of Th17 cells by 33. 85%-63.00% and the expression of RORγt in a dose-dependent manner ( P < 0.01). Simultaneously, T. hemsleyanum obviously elevated the levels of IL-35 and TGF-β, accompanied by the increasing expression of Foxp3 in a dose-dependent manner and the enhancement of Treg cells proportion ( P < 0.01). Furthermore, T. hemsleyanum could regulate the levels of 22 endogenous metabolites involved in linoleic acid, arachidonic acid, and glycerophospholipid metabolism. Comprehensively, the therapeutic effect of T. hemsleyanum on sarcoidosis was achieved by suppressing the inflammatory response, maintaining Th17/Treg immune homeostasis and regulating abnormal glycerolipid metabolism.