Glycyrrhizin Combined with Electroacupuncture Relieves Parkinson's Disease Progression Through the Inhibition of HMGB1-mediated Microglial Autophagy.

Abstract

BACKGROUND: Microglial autophagy is closely related to the development of Parkinson's disease (PD). The objective of this research was to investigate the effect of glycyrrhizin (Gly) combined with electroacupuncture (EA) on PD mice and its potential regulation of microglial autophagy. METHODS: A PD mouse model was constructed using the administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), followed by the administration of Gly to PD mice and EA. The activation of BV2 cells was triggered by lipopolysaccharide (LPS). Western blotting, immunofluorescence, flow cytometry, Nissl staining, and immunohistochemistry were used to investigate the molecular mechanism that governs how microglial autophagy levels influence PD progression. RESULTS: Elevated levels of HMGB1 were observed in both patients with PD and PD mice. Gly inhibited HMGB1 expression and extracellular secretion by increasing SIRT1 activity and subsequently inhibit BV2 autophagy. EA inhibited the autophagy of microglia in PD mice by inhibiting the activation of TRPV1 and reducing the expression of HMGB1 in vivo. Gly combined with EA downregulated HMGB1 expression, inhibited microglial autophagy and improved the PD process, resulting in better effects than Gly or EA alone. CONCLUSION: Gly combined with EA can reduce the level of autophagy in microglia by downregulating HMGB1, thereby improving the PD process and providing a theoretical basis for the clinical treatment of PD.