Exploring the Anti-Cancer Properties of Nasturtium officinale L. via the HOTAIR/miR-124/Notch1 Pathway in Rat Hepatocellular Carcinoma: An Investigation Using Biochemical, Molecular, Immunohistochemical, and Histopathological Methods

This study aimed to explore the potential of Nasturtium officinale L. leaves extract (NOLE) in safeguarding hepatocytes against N-diethylnitrosamine (DEN)-induced hepatocellular carcinoma (HCC) by investigating its effects on biochemical, molecular, and antioxidant pathways.The study also delved into NOLE's role in modulating the HOTAIR/miR-124/Notch1 axis pathway.In this study, 50 Wistar rats were divided into five groups (n=10/group): normal, HCC-induced (100 mg/kg DEN), HCC rats treated with 100 and 200 mg/kg DEN + NOLE, and normal rats treated with 200 mg/kg NOLE.At the study's conclusion, serum levels of liver function markers (such as albumin, total protein, bilirubin, C-reactive protein, ALT, AST, and ALP), inflammatory cytokines (IL-6, IL-1b, IL-10, and TNF-a), and oxidative parameters [including glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT) enzyme activity, and nitric oxide (NO) levels] were assessed.The levels of HOTAIR, miR-124, Notch1, and Jagged1 genes and proteins in liver tissue were measured.Immunohistochemical analysis was used to evaluate P53-positive cells in liver hepatocytes.DEN administration led to significant alterations in body and liver weight, serum liver enzymes, antioxidant levels, inflammatory markers, and expression of genes/proteins related to the HOTAIR/miR-124/Notch1 axis in liver pathways.NOLE exhibited dose-dependent effects in mitigating these changes, notably enhancing weight, liver health, antioxidant capacity, and inflammatory responses, especially at the 200 mg/kg dosage.Histopathological assessments revealed structural improvements in liver tissue with NOLE treatment.In conclusion, our study highlights the potential of NOLE in exerting anti-cancer effects against DEN-induced HCC.