Vitexin mitigates AIM2 inflammasome-mediated mitochondrial dysfunction and neuroinflammation in chronic constriction injury induced neuropathy model

Abstract

The chronic constriction injury (CCI) replicates trauma-induced peripheral neuropathy by increasing oxidative-nitrosative stress, inflammation and mitochondrial dysfunction through compression of the peripheral nerves. Vitexin, a natural flavonoid was investigated for its effect on mitochondrial dysfunction -induced AIM2 inflammasome activation in CCI induced neuropathic pain in rats. The study was conducted through in vitro and in-vivo methods through vitexin treatment to LPS (1.5 μg/mL) exposed SHSY5Y cells as well as over CCI induced SD rats (3 mg/kg/day and 6 mg/kg/day, i.p.,14 days) Neuropathic pain was assessed through several behavioral evaluations. For understating the molecular mechanism, we investigated the impact of vitexin on oxidative stress, mitochondrial dysfunction, and molecular protein expressions. Our studies showed altered behaviour and functional parameters, including hyperalgesia, allodynia, damaged sciatic functions as well as increased oxidative stress, and activation of inflammasomes such as ASC, NF-κB, AIM2, and caspase 1. Furthermore, the expression of SIRT1, SIRT3, PGC-1α, and TFAM was reduced, indicating mitochondrial dysfunction. Treatment with vitexin prevented behavioral hypersensitivity, improved sciatic functions, decreased oxidative stress and inhibited AIM2 associated other inflammasome activation and mitochondrial dysfunction both in-vitro and in-vivo. Vitexin, showed neuroprotective potential by ameliorating mitochondrial dysfunction, and associated AIM2 inflammasome activation in experimental trauma induced neuropathic pain. This research offers a detailed understanding of the mechanisms involved in pathophysiology of CCI induced neuropathic pain and suggest that targeting mitochondrial dysfunction and AIM2 inflammasome may be beneficial in the management of neuropathic pain.