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

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 < .05). ALOF extract in both doses of 250 and 500 mg/kg in cotreatment with SIL caused a significant (p < .05) decrease in the p53‐positive cells and a significant (p < .05) increase in Bcl‐2‐positive cells. Therefore, ALOF was able to modulate the proliferation of cancer cells and protect normal cells through the regulation of Bax/Bcl‐2/p53 and PI3K/Akt/mTOR signaling pathways. It seems that ALOF can be used as a prodrug or complementary treatment in the protection of hepatocytes in induced damages caused by carcinogens.