Ginsenoside Rg1 improves chronic neuropathic pain by inhibiting NLRP3 inflammasome activation and cell pyroptosis in microglia

Ethnopharmacological relevance: Panax notoginseng, documented in Sheng Nong's Herbal Classic, has long been used to relieve pain. Its major bioactive component, ginsenoside Rg1, exhibits diverse pharmacological activities, but its role in chronic neuropathic pain (CNP) remains poorly understood.

Aim of the study: This study endeavors to decipher the analgesic functions of Ginsenoside Rg1 and explore the molecular mechanisms that underlie them.

Materials and methods: Sciatic nerve ligation-induced CCI was employed to create a neuropathic pain mouse model for evaluating Rg1's impact. The standard Von Frey filament test measured limb withdrawal thresholds to quantify Rg1's impact on neuropathic pain. Immunofluorescence and immunohistochemical staining determined Iba-1, NLRP3, and ROS cellular distribution and expression. Western blot analysis detected protein expressions of NLRP3-signaling, Mitophagy, and Pyroptosis - related factors.

Results: To evaluate the effect of Rg1, a mouse model of neuropathic pain was established via CCI induced by sciatic nerve ligation. Mechanistically, Rg1 promoted microglial Mitophagy through TFEB nuclear translocation. Suppressed NLRP3 expression and reduced Caspase-1 p10 and IL-1β p17 secretion confirmed NLRP3 inhibition, which 3-methyladenine reversed. Additionally, Rg1 enhanced Mitophagy by scavenging ROS, restoring mitochondrial potential, and improving abnormal mitochondria.

Conclusion: Our findings suggest that Ginsenoside Rg1 has potential as a therapeutic agent for CNP, as it effectively alleviates CNP in rats via promoting microglial Mitophagy, inhibiting NLRP3 inflammasome activation, and suppressing microglial Pyroptosis.

Chronic neuropathic pain; Ginsenoside Rg1; Microglia; Mitophagy; NLRP3 inflammasome; TFEB.