Oroxylin A induces apoptosis of activated hepatic stellate cells through endoplasmic reticulum stress. - GreenMedInfo Summary
Oroxylin A induces apoptosis of activated hepatic stellate cells through endoplasmic reticulum stress.
Apoptosis. 2019 Dec ;24(11-12):905-920. PMID: 31538267
Mianli Bian
Hepatic stellate cell (HSC) activation plays an indispensable role in hepatic fibrosis. Inducing apoptosis of activated HSCs can attenuate or reverse fibrogenesis. In this study, we initially found that oroxylin A (OA) protected CCl-induced liver injury accompanied by endoplasmic reticulum stress (ERS) activation of HSCs in mice. In vitro, OA treatment markedly reduced fibrogenesis by modulating extracellular matrix synthesis and degradation. OA inhibited cell proliferation and induced cell cycle arrest of HSCs at S phase. Further, OA was observed to induce HSC apoptosis, as indicated by caspase activation. Using the eIF2α dephosphorylation inhibitor salubrinal, we found that ERS pathway activation was required for OA to induce HSC apoptosis. ERS-related proteins were significantly upregulated by OA treatment, and salubrinal abrogated the effects of OA on HSCs. Thus, we inferred that OA attenuated HSC activation bypromoting ERS. In vivo, inhibition of ERS by salubrinal partly abrogated the hepatoprotective effect of OA in CCl-treated mice. In conclusion, our findings suggest a role for ERS in the mechanism underlying amelioration of hepatic fibrosis by OA.