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

Aims: 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. Main methods: Rats were treated with Glyc (50 mg/kg, i.p.) for 3 weeks and 3-NP (10 mg/kg, i.p.) was admin-istered at the latter 2 weeks alongside to induce HD. Key findings: 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 inflam-mation. 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-Kappa B p65 signaling off, reduced IL-6, IL-beta, TNF-alpha, 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. Significance: Accordingly, the current study demonstrated a promising neuroprotective effect of Glyc against experimentally induced HD through alleviating deleterious events by diverse mechanisms.

Automated summary

The study reveals the neuroprotective effect of Glycyrrhizin (Glyc) against experimentally induced Huntington's disease (HD), which is achieved through diverse mechanisms including improvement of neurobehavioral deficits, attenuation of oxidative stress, and reduction of inflammation. The findings provide valuable insights into the potential mechanism of action of Glyc against HD.