Pretreatment of artesunate promoted hepatocyte proliferation by activating the PI3K/Akt/mTOR signaling pathway in mice

Purpose:  Artesunate (ART) has been implicated in regulating the many processes of liver injury, but its roles in liver regeneration still need to be illustrated.

Methods:  In the present study, ART was used to pretreat hepatocyte cell line NCTC1469 to study the effect of ART on hepatocyte proliferation in vitro. Furthermore, the potency of ART as a regimen to promote liver regeneration and restore liver function was evaluated following partial hepatectomy (PH) on C57BL/6 mice.

Results:  ART concentration-dependently promoted hepatocyte proliferation and reduced apoptosis. Cell cycle and Ki-67 immunohistochemical analyses demonstrated that ART supplementation promoted the proliferation of hepatocytes and accelerated liver regeneration. Our results provided evidence that ART improved liver function in a dose-dependent manner, as indicated by decreased serum alanine aminotransferase, aspartate aminotransferase, and increased albumin, and hepatocyte growth factor levels in PH mice. Meanwhile, ART promoted the PI3K/Akt/mTOR signaling in NCTC1469 cells and liver tissue of PH mice. In addition, PI3K inhibitor LY294002 blocked the promotion effect of ART on hepatocyte proliferation and cell cycle progression.

Conclusion:  ART promoted hepatocyte proliferation via activation of the PI3K/Akt/mTOR pathway, which was beneficial to liver regeneration of PH-induced liver injury.

Key words
Artesunate; Cell Proliferation; Liver Regeneration; TOR Serine-Threonine Kinases