Standardized Tribulus terrestris L extract ameliorates neuropathic pain through anti-inflammatory and GABAergic mechanism – In Vitro and In Vivo studies

Neuropathic pain resulting from peripheral nerve injury led to severe distress in patients. It leads to loss of sensory and motor function, including altered autonomic nerve function. The present study is aimed to explore the effects of Tribulus terrestris. L (TT) in the chronic constriction injury (CCI) pain model to elucidate its role in peripheral and central mediated analgesic response. The anti-inflammatory effect of Tribulus terrestris L was explored using LPS induced inflammation model in RAW 264.7 cell lines. Furthermore, to explore the TT activity in in vivo, 30 wistar rats were randomly divided into 5 groups (A) Sham Control, (B) CCI, (C) CCI + pregabalin, (D) CCI + Tribulus terrestris L (50 mg/kg, p.o.), (E) CCI + Tribulus terrestris L (100 mg/kg, p.o.). The rats of respective treatment groups treated with pregabalin (10 mg/kg, p.o.) and Tribulus terrestris L (50, 100 mg/kg, p.o.) for 21 days. Simultaneously mechanical hyperalgesia, allodynia, sciatic functional index was measured on 7, 14 and 21 day. In the end of the study inflammatory cytokines, caspase 3 activity were performed in sciatic nerve and spinal cord. To understand the extent of nerve degradation histopathological analysis for sciatic nerve was performed. TT was subjected to GC-MS analysis which confirms the presence of β carboline alkaloids and scopoletin. The in vitro results revealed the Tribulus terrestris L has anti-inflammatory property that is evidenced through the regulation inflammatory cytokines, NO levels and iNOS & COX2 gene expressions. Rats in CCI group exhibited a significant analgesic response in mechanical hyperalgesia and allodynia. In contrast, Tribulus terrestris L recovered the loss of sciatic functional index and sciatic nerve conduction velocity. The elevated pro-inflammatory cytokines (spinal cord and sciatic nerve) and excitatory amino acids (EAA) (cerebral tissue) caused by CCI were significantly reduced by TT. The altered activity of glutamic acid decarboxylase (GAD) and caspase 3 enzymes were regulated with TT treatment. Histopathological examination of sciatic nerve degeneration of the nerve fibers with inflammatory infiltrates are restored in treatment groups. In unison, the present study concludes that TT showed protective effect in the LPS induced inflammation in RAW 264.7 cells and CCI rats. • β carboline alkaloids and scopoletin were present in the standardized extract • TT attenuated LPS induced inflammation in RAW 264.7 cell line • TT exhibited analgesic activity in peripheral nerve injury (CCI) • TT exhibited better analgesic activity in mechanical hyperalgesia than allodynia • TT regulated the release of cytokines, EAA and expression of COX 2 enzyme