Baicalein, isolated from Scutellaria baicalensis, protects against endothelin-1-induced pulmonary artery smooth muscle cell proliferation via inhibition of TRPC1 channel expression

Abstract

Ethnopharmacological relevanceWe investigated the antiproliferative effects of baicalein, isolated from Scutellaria baicalensis (Huang-qin), on ET-1-mediated pulmonary artery smooth muscle cells (PASMCs) proliferation and the mechanisms underlying these effects. Materials and methodsIntrapulmonary artery smooth muscle cells were isolated and cultured from female Sprague-Dawley rats and used during passages 3–6. The proliferation of PASMCs was quantified by cell counting and XTT assay. The protein expression of TRPC1 and PKCα were determined by western blotting. The cell cycle pattern was assayed by flow cytometry. The intracellular calcium concentrations ([Ca2+]i) were measured using the fluorescent indicator fura-2-AM and flow cytometry. ResultsBaicalein (0.3–3μM) inhibited PASMCs proliferation, promoted cell cycle progression, enhanced [Ca2+]i levels, increased capacitative Ca2+ entry (CCE), upregulated the canonical transient receptor potential 1 (TRPC1) channel and membrane protein kinase Cα (PKCα) expression induced by ET-1 (0.1μM). The PKC activator PMA (1μM) reversed the inhibitory effects of baicalein on ET-1-induced upregulation of TRPC1 expression and S phase accumulation, while the PKC inhibitor chelerythrine (1μM) potentiated baicalein-mediated G2/M phase arrest and TRPC1 channel inhibition. ConclusionOur findings suggest that baicalein protects against ET-1-induced PASMCs proliferation via modulation of the PKC-mediated TRPC channel.