Potential neuroprotective effect of the HMGB1 inhibitor Glycyrrhizin in neurological disorders.

Glycyrrhizin (Glycyrrhizic Acid), a bioactive triterpenoid saponin found in Glycyrrhiza glabra, has been used for a long time in traditional medicine. Glycyrrhizin possesses a plethora of pharmacological activities including anti-inflammatory, antioxidant, anti-microbial and anti-ageing potential. It is a well-established pharmacological inhibitor of high mobility group box 1 (HMGB1), a ubiquitous protein with pro-inflammatory cytokine-like activity. HMGB1 contributes to an array of inflammatory diseases when released extracellularly, primarily via the activation of cell signaling upon binding to receptor for advanced glycation end products (RAGE) and toll-like receptor 4 (TLR4). HMGB1 neutralization strategies have demonstrated disease-modifying outcomes against several pre-clinical models of neurological disorders, mainly through inhibition of HMGB1 expression and release. In this review, we aim to enlighten the therapeutic potential of glycyrrhizin against different neurological disorders. Current research studies demonstrate the therapeutic potential of glycyrrhizin against several HMGB1-mediated pathological conditions including Traumatic brain injury, Neuroinflammation and associated conditions, Epileptic seizures, Alzheimer's disease and related pathology, Parkinson's disease and Multiple sclerosis. Glycyrrhizin's effects in neurological disorders are mainly attributed to attenuation of neuronal damage by inhibiting HMGB1 expression and translocation as well as by downregulating expression of inflammatory cytokines. Current scientific evidence indicates that glycyrrhizin might be a promising therapeutic alternative that could overcome the limitations of current treatment strategy against these neurological disorders discussed herein mainly via halting disease progression. However, future research is warranted for deeper exploration of the precise underlying molecular mechanism as well as for clinical translation.