Rosmanol Effectively Prevents Diethylnitrosamine-induced Hepatocellular Carcinoma in Rats by Regulating the PI3K/Akt Signaling Pathway

Abstract

Background: Hepatocellular carcinoma (HCC) is the third principal reason for tumor-linked fatalities globally. There is no effective cure for HCC due to rapid progression and poor prognosis. Rosmanol (RM) is a phenolic diterpene antioxidant that exhibits anti-inflammatory and anticancer properties.Objectives: This research aims to examine the chemopreventive efficacy of RM on the PI3K/Akt pathway as a potential mechanism for its protective effect against N-diethylnitrosamine (DEN)-induced HCC.Materials and Methods: Wistar albino male rats were separated into four sets: normal control (NC); DEN-induced HCC model; DEN+RM (40 mg/kg bw); and RM (40 mg/kg bw) alone. To evaluate the chemopreventive mechanism, we assessed the change in body weight, liver weight, hepatotoxicity markers, antioxidant enzymes, lipid peroxidation, proliferation proteins, cytokines, histopathology, and western blot. Results and Conclusion: Our data revealed that RM could reduce the loss of body weight, liver weight, toxicity enzymes, oxidative stress, inflammation, and restructuring of the hepatocellular architecture against DEN-stimulated HCC rats. RM-alone treated rats exhibited comparable activity with NC. Furthermore, RM attenuates PCNA and cyclin-D1 protein expression by the regulation of the PI3K/Akt pathway. The possible chemopreventive activities of RM may be owing to its antioxidative, anti-inflammatory, and antiproliferative effects. Thus, RM may aid as an innovative remedial agent for HCC treatment.

Keywords: Rosmanol; chemoprevention; hepatocellular carcinoma; N-diethylnitrosamine; PI3K/Akt pathway