Glycyrrhizic Acid Protects against Thioacetamide-Induced Hepatic Fibrosis in Rats by Inhibition of HMGB1 and its crosstalk with Autophagy-Related Protein Beclin-1 | ||||
| Bulletin of Egyptian Society for Physiological Sciences | ||||
| Volume 44, Issue 4, October 2024, Page 256-271 PDF (948.49 K) | ||||
| Document Type: Original Article | ||||
| DOI: 10.21608/besps.2024.312629.1173 | ||||
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| Authors | ||||
Seham Z. Nassar1; NADA A.H. Soliman 2; Shaymaa A. Abdulmalek 3; Rania G. Aly 4; Soha Elatrebi 5; Eman A. Allam  6
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| 1Department of Medical Physiology, Faculty of Medicine, Alexandria University, Alexandria, Egypt | ||||
| 2Medical Biochemistry department, Faculty of Medicine, Alexandria University, Egypt | ||||
| 3Department of Biochemistry, Faculty of Science, Alexandria University, Egypt | ||||
| 4Department of Pathology, Faculty of Medicine, Alexandria University, Alexandria, Egypt | ||||
| 5Department of Clinical Pharmacology, Faculty of Medicine, Alexandria University, Egypt | ||||
| 6Medical physiology department, faculty of medicine, Alexandria university | ||||
| 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. | ||||
| Keywords | ||||
| Autophagy; Hepatic fibrosis; Beclin1; High mobility group box 1 (HMGB1); Glycyrrhizic acid | ||||
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