Alantolactone mitigates thioacetamide-induced liver fibrosis in mice by inhibiting TLR4/MyD88/NF-κB axis
Year: 2025
Type: article
Abstract: Objective: To explore the effect of alantolactone on thioacetamide-induced liver fibrosis in mice as well as elucidate its underlying mechanism. Methods: Animals were divided into 5 groups: the control, the thioacetamide group (150 mg/kg/twice weekly), the thioacetamide groups treated with alantolactone (5 and 10 mg/kg) or silymarin (50 mg/kg), respectively. All treatments were continued for 6 successive weeks, followed by collection of sera and tissue samples. Biochemical, histological, and immunohistochemical analyses were performed to examine the hepatoprotective effects of alantolactone. Results: Alantolactone ameliorated thioacetamide-induced hepatic impairment and prevented the rise of serum activities of liver enzymes. Its hepatoprotective effect was further confirmed by histological examinations. Moreover, alantolactone lowered the expression of transforming growth factor-beta 1 and alpha-smooth muscle actin, hydroxyproline content as well as COL1A1 mRNA expression. It restored antioxidant balance and inhibited thioacetamide-induced upregulated expression of interleukin-1 beta, interleukin-6, and tumor necrosis factor-alpha, Toll-like receptor 4 (TLR4), myeloid differentiation primary response 88 (MyD88), and nuclear factor kappa B (NF-κB). Conclusions: Alantolactone protects against thioacetamide-induced liver fibrosis in mice by reducing collagen deposition, oxidative stress, and inflammation. These effects are mediated, at least partly, by the inhibition of TLR4/MyD88/NF-κB axis.
Authors: Haifa Almukadi, Nabih N. Alotaibi, Rasheed A. Shaik, Ashraf B. Abdel-Naim, Ahmed Esmat, Basma G. Eid
Institutions: King Abdulaziz University, Ministry of Health
Language: English
Subfield: Hepatology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W4412958566