Protective effects of Althaea officinalis L. extract against N‐diethylnitrosamine‐induced hepatocellular carcinoma in male Wistar rats through antioxidative, anti‐inflammatory, mitochondrial apoptosis and PI3K/Akt/mTOR signaling pathways

Abstract Hepatocellular carcinoma is the fourth cause of death due to cancer and includes 90% of liver tumors. Therefore, in this study, it was tried to show that Althaea officinalis L. flower extract (ALOF) can protect hepatocytes against N‐diethylnitrosamine (DEN)‐induced hepatocellular carcinoma. Totally, 70 Wistar rats were divided into seven groups (n = 10/group) of sham, DEN, treatment with silymarin (SIL; DEN + SIL), treatment with ALOF (DEN + 250 and 500 ALOF), and cotreatment with SIL and ALOF (DEN + SIL + 250 and 500 ALOF). At the end of the study, the serum levels of liver indices (albumin, total protein, bilirubin, C‐reactive protein, ALT, AST, and ALP), inflammatory cytokines (IL‐6, IL‐1β, IL‐10, and TNF‐α), and oxidants parameters (glutathione peroxidase [GPx], superoxide dismutase [SOD], catalase [CAT] activity along with nitric oxide [NO] levels) were evaluated. The level of Bax, Bcl‐2, Caspase‐3, p53, PI3K, mTOR, and AKT genes were measured. ALOF in cotreatment with SIL was able to regulate liver biochemical parameters, improve serum antioxidant indices, and decrease the level of proinflammatory cytokines significantly (p