18β-glycyrrhetinic acid accelerates liver regeneration after partial hepatectomy in mice

• 18β-glycyrrhetinic acid accelerated liver regeneration after partial hepatectomy. • 18β-glycyrrhetinic acid facilitated hepatocyte proliferation by promoting the G1/S phase transition of the cell cycle. • Accelerated liver regeneration by 18β-glycyrrhetinic acid was associated with activation of MAPK/ERK signaling pathway. 18β-Glycyrrhetinic acid (18β-GA), a key bioactive triterpenoid in Glycyrrhiza uralensis Fisch, is recognized for its hepatoprotective effects in liver injury. However, the role of 18β-GA on liver regeneration after partial hepatectomy (PHx) remains unknown. This study aims to investigate the effects and underlying mechanisms of 18β-GA in facilitating liver regeneration after PHx. PHx mice were orally gavaged with 18β-GA for 7 days. The promotion of 18β-GA on liver regeneration was evaluated by liver/body weight ratio, BrdU, Ki67 and PCNA. Cell cycle transition was performed to evaluate hepatocyte proliferation. The effects of 18β-GA on protein and mRNA expression levels within the MAPK/ERK signaling pathway were systematically evaluated. 18β-GA significantly accelerated liver mass recovery and promoted hepatocyte proliferation after PHx. 18β-GA treatment facilitated the cellular G1/S phase transition and upregulated the expression of the proliferation-related protein CCND1, PCNA and p-Rb. Moreover, 18β-GA significantly increased the levels of growth factors including Hgf , Egf , Tgf-α and Hb-egf . Furthermore, mechanistic investigations suggested that 18β-GA activated the MAPK/ERK signaling pathway and increased the expression of p-ERK1/2, c-JUN, c-FOS, and c-MYC in vitro and in vivo . Application of ERK inhibitor U0126 effectively abolished 18β-GA-induced activation of MAPK/ERK signaling pathway. 18β-GA exhibited a significant promoting effect on liver recovery following PHx, potentially through modulation of the MAPK/ERK signaling pathway to accelerate liver regeneration.