Verbascum thapsus L. ethanol fraction mitigates CCl4-induced hepatic damage via inhibition of TNFα-NF-κB signaling and oxidative stress in rats

Objective: To evaluate the hepatoprotective effects of the ethanol fraction of Verbascum thapsus L. (EFVT) against CCl 4 -induced liver injury and elucidate its underlying mechanisms. Methods: The assessment of antioxidant properties and cell viability was conducted using the 2,2-diphenyl-1-picrylhydrazyl assay and HepG2 cells, respectively. The in vivo hepatoprotective efficacy of EFVT was evaluated in a rat model of carbon tetrachloride (CCl 4 )-induced liver injury by determining biochemical parameters, and oxidative stress- and inflammation-related markers. Gas chromatography-mass spectrometry was also employed for the qualitative analysis of its phytochemical composition. Results: GC-MS analysis of EFVT revealed the presence of several bioactive compounds such as 3 methyl mannoside and 9,12-octadecadienoic acid. Oral administration of EFVT significantly mitigated CCl 4 -induced liver injury, as evidenced by reduced levels of total bilirubin, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, and malondialdehyde, boosted activities of catalase and superoxide dismutase, as well as enhanced glutathione levels. Histopathological examinations indicated EFVT restored abnormal liver architecture and reduced inflammation. Additionally, EFVT substantially downregulated the mRNA levels of IL-6, IL-1β, TNF-α , and NF-κB , and upregulated IL-10 expression. Conclusions: These findings underscore the therapeutic potential of EFVT in ameliorating liver damage associated with oxidative stress, providing scientific validation for its traditional utilization in ethnomedicine.