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

Abstract

Objective: To evaluate the hepatoprotective effects of the ethanol fraction of Verbascum thapsus L. (EFVT) against CCl4-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 (CCl4)-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 CCl4-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.

Keywords

Liver injury / Verbascum thapsus / CCl₄ / Xenobiotics / Oxidative stress / HepG2 / NF-κB

Conflict of interest statement

Hafiz Muhammad Zubair is an editorial board member of this journal but has no role in the decision to publish this article. No potential conflict of interest relevant to this article was reported.

Funding

The study received no extramural funding.

Data availability statement

The data supporting the findings of this study are available from the corresponding author upon request.

Authors’ contributions

AA carried out the animal study, performed biochemical experiments, and drafted the original manuscript. HMZ supervised the project, managed research administration, contributed to conceptualization, and performed qPCR. FA conducted MTT assays and phytochemical screening tests. NUR and SMI prepared fractions and assisted in statistical analyses. SK carried out validation. AS performed histological analysis and review. UID, MA, and MSM contributed to manuscript review and editing.

Publisher’s note

The Publisher of the Journal remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Acknowledgments

The authors would like to thank their respective universities for the support. Special thanks are extended to Mr. Muhammad Naveed Sheas and Dr. Samiullah Malik from The Islamia University of Bahawalpur for their assistance in plant collection.

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