Capsaicin Attenuates Hepatic Stellate Cells Activation by Inhibiting the PI3K/AKT/mTOR Pathway

Objectives: To investigate the inhibitory effect of capsaicin on the activation of hepatic stellate cells (HSCs) and elucidate the underlying mechanism. Methods: Cultured HSCT6 cells were treated with capsaicin at various concentrations. The Cell Counting Kit-8 (CCK-8) assay was performed to detect cell proliferation, and western blot analysis was used to evaluate the expression of fibrotic and apoptotic proteins, and the activation of the PI3K/AKT/mTOR pathway. Results: Capsaicin dose-dependently inhibited HSC cell proliferation and suppressed HSC cell fibrosis, as demonstrated by reduced protein levels of Fibronectin, Collagen I, Collagen III, α-SMA, and tissue inhibitors of metalloproteinase 1 (TIMP-1). Furthermore, capsaicin-induced HSC cell apoptosis is characterized by decreased Bcl-2 levels and increased Bax protein expression. Capsaicin also inhibited HSC activation by downregulating epidermal growth factor (EGF)-induced PI3K/AKT/mTOR signaling. Additionally, the inhibitory effects of capsaicin were enhanced with PI3K inhibitor LY294002 in HSCs. Conclusions: Capsaicin attenuates HSC activation by inhibiting the PI3K/AKT/mTOR pathway.