Scoparone inhibits the development of hepatocellular carcinoma by modulating the p38 MAPK/Akt/NF‐κB signaling in nonalcoholic fatty liver disease mice

Abstract

Background and study aimThe mechanisms underlying the progression of non‐alcoholic fatty liver disease (NAFLD) into hepatocellular carcinoma (HCC) remains confusing and the therapeutics approaches are also challenging. Here, we aimed to investigate the effects of scoparone on the treatment of HCC stemmed from NAFLD and the underlying mechanisms.Materials and methodsA model of NAFLD‐HCC was created in mice, and these mice were treated with scoparone. Biochemical assays were conducted to assess the levels of biochemical markers. Tumors were evaluated through morphological examination. Histopathological analyses were performed using oil red O, Hematoxylin and Eosin, and Masson coloration assays. Immunohistochemistry (IHC) and RT‐PCR were performed to analyze protein expression and measure mRNA expression levels, respectively.ResultsScoparone could ameliorate the pathological alterations observed in NAFLD‐HCC mouse model. IHC analysis indicated an upregulation of NF‐κB p65 expression in both NAFLD and NAFLD‐HCC models, which was subsequently reverted by scoparone administration. Furthermore, scoparone treatment resulted in a reversal of the increased mRNA expression levels of NF‐κB target genes, including TNF‐α, MCP‐1, iNOS, COX‐2, NF‐κB, and MMP‐9, which were originally elevated in the NAFLD‐HCC condition. Additionally, scoparone exhibited a capacity to counteract the activation of the MAPK/Akt signaling in the NAFLD‐HCC model.ConclusionThese findings suggest that scoparone holds promise as a potential therapeutic agent for NAFLD‐associated HCC, and its model of action may involve the regulation of inflammatory pathways governed by the MAPK/Akt/NF‐κB signaling cascade.

Pharmacological therapy of metabolic dysfunction-associated steatotic liver disease-driven hepatocellular carcinoma

“…The most recent study showed that scoparone attenuates the pathological alterations observed in MASLD-HCC mouse models. Scoparone inhibits activation of mitogen-activated protein kinase (MAPK)/Akt signaling and reverses upregulation of NF-κB p65 and its target genes, including NF-κB, TNF-α, cyclooxygenase (COX-2), MCP-1, iNOS, and MMP-9, in MASLD-HCC models (Ye et al, 2023). These results suggest that scoparone is a potential therapeutic agent for MASLD-HCC as it inhibits MAPK/Akt/NF-κB-mediated inflammatory pathways.…”