Glycyrrhizic Acid Protects against Thioacetamide-Induced Hepatic Fibrosis in Rats by Inhibition of HMGB1 and its crosstalk with Autophagy-Related Protein Beclin-1

Nassar, Seham Z.; Soliman, NADA A.H.; Abdulmalek, Shaymaa A.; Aly, Rania G.; Elatrebi, Soha; Allam, Eman A.

doi:10.21608/besps.2024.312629.1173

Glycyrrhizic Acid Protects against Thioacetamide-Induced Hepatic Fibrosis in Rats by Inhibition of HMGB1 and its crosstalk with Autophagy-Related Protein Beclin-1

Document Type : Original Article

Authors

¹ Department of Medical Physiology, Faculty of Medicine, Alexandria University, Alexandria, Egypt

² Medical Biochemistry department, Faculty of Medicine, Alexandria University, Egypt

³ Department of Biochemistry, Faculty of Science, Alexandria University, Egypt

⁴ Department of Pathology, Faculty of Medicine, Alexandria University, Alexandria, Egypt

⁵ Department of Clinical Pharmacology, Faculty of Medicine, Alexandria University, Egypt

⁶ Medical physiology department, faculty of medicine, Alexandria university

10.21608/besps.2024.312629.1173

Abstract

Background: The pathogenesis of hepatic fibrosis (HF) involves hepatic stellate cells (HSC) activation to myofibroblasts that synthesize and secrete extracellular matrix (ECM). Autophagy has a role in the activation of quiescent HSCs. Beclin 1 regulates the formation of early autophagosome; however, its activity could be inhibited by binding to Bcl-2. The binding of the latter to Beclin 1 is mediated by a chromatin-associated nuclear protein; the High mobility group box 1 (HMGB1). This study aimed to analyze the effect of inhibiting Beclin 1 autophagy pathway using HMGB1 protein inhibitor, Glycyrrhizic acid (GA), on the progression of HF in a thioacetamide (TAA) induced rat model.
Methods: HF was induced in 20 Wistar male rats; by TAA injection intraperitoneally twice weekly for eight consecutive weeks; divided into two random groups: untreated HF group and GA treated group. Ten rats served as controls.
Results: The current work illustrated the inhibitory effect of GA on HF as evidenced by histopathological examination, reduction of oxidative stress, inflammatory and fibrotic markers like IL-1ß, TGF-β and α-SMA aligned with a downregulation in MMP-2 and TIMP expression. Inhibition of autophagy was also evident by decreased expression of both Beclin1 and HMGB1.
Conclusion: GA acts as an inhibitor of the beclin-1 autophagy pathway and this could be a preventive therapy against development of HF.

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