Glycyrrhizin prevents 3-nitropropionic acid-induced neurotoxicity by downregulating HMGB1/TLR4/NF-κB p65 signaling, and attenuating oxidative stress, inflammation, and apoptosis in rats

• DOI: 10.1016/j.lfs.2022.121317
• Publication Date: 2022-12-23T03:08:09Z
• Authors: Abdallah M. Gendy; Hagar M. El-Sadek; Mohamed M. Amin; Kawkab A. Ahmed; Mohamed Kotb El-S...; Alaadin E. El-Haddad; Ayman Soubh
• Keywords: Inflammation; 0301 basic medicine; Body Weight; NF-kappa B; Apoptosis; Glycyrrhizic Acid; Rats; 3. Good health; Toll-Like Receptor 4; Oxidative Stress; 03 medical and health sciences; Huntington Disease; Animals; HMGB1 Protein

Glycyrrhizin (Glyc) is a saponin triterpenoid that has signified its efficacy against Huntington's disease (HD). Nonetheless, its mechanism has not been fully clarified. Accordingly, this study was designed to evaluate the plausible mechanism of action of Glyc against 3-nitropropionic acid (3-NP)-induced HD.Rats were treated with Glyc (50 mg/kg, i.p.) for 3 weeks and 3-NP (10 mg/kg, i.p.) was administered at the latter 2 weeks alongside to induce HD.Animals exposed to 3-NP revealed a reduction in body weight, neurobehavioral abnormalities, and various deleterious effects related to overexpression of HMGB1 such as oxidative stress, apoptosis, and inflammation. Promisingly, Glyc administration provided valuable effects by reversing the decline in body weight with improved neurobehavioral deficits. Ameliorating oxidative stress via restoring GSH, SOD, and Nrf2 alongside with MDA suppression was evident. Furthermore, Glyc switched the HMGB1/TLR4/NF-κB p65 signaling off, reduced IL-6, IL-β, TNF-α, caspase-3, and increased Bcl-2 as well as BDNF. All these beneficial effects were mirrored by a better histopathological picture upon using Glyc that suppressed gliosis by reducing GFAP expression as observed in the immunohistochemistry results.Accordingly, the current study demonstrated a promising neuroprotective effect of Glyc against experimentally induced HD through alleviating deleterious events by diverse mechanisms.