Solasodine Containing Solanum torvum L. Fruit Extract Prevents Chronic Constriction Injury-Induced Neuropathic Pain in Rats: In Silico and In Vivo Evidence of TRPV1 Receptor and Cytokine Inhibition

Mol Neurobiol. 2023 Sep;60(9):5378-5394. doi: 10.1007/s12035-023-03412-w. Epub 2023 Jun 14.

Abstract

This study aimed to assess the efficacy of ethanolic extract of Solanum torvum L. fruit (EESTF) containing solasodine in treating chronic constriction injury (CCI)-induced neuropathic pain in rats. Three-dimensional (3D) simulation studies of solasodine binding were conducted on the TRPV1 receptor, IL-6, and TNF-α structures. For in vivo justification, an assessment of behavioral, biochemical, and histological changes was designed after a CCI-induced neuropathic pain model in rats. On days 7, 14, and 21, CCI significantly increased mechanical, thermal, and cold allodynia while producing a functional deficit. IL-6, TNF-α, TBARS, and MPO levels also increased. SOD levels of catalase and reduced glutathione levels also decreased. Administration of pregabalin (30 mg/kg, oral), solasodine (25 mg/kg, oral), and EESTF (100 and 300 mg/kg, oral) significantly reduced CCI-induced behavioral and biochemical changes (P < 0.05). The protective nature of EESTF was also confirmed by histological analysis. Capsaicin, a TRPV1 receptor agonist, abolished the antinociceptive effects of EESTF when used previously. From the observations of the docking studies, solasodine acted as an antagonist at TRPV1, whereas the docking scores of solasodine against TNF-α and IL-6 were reported to be -11.2 and -6.04 kcal/mol, respectively. The attenuating effect of EESTF might be related to its antagonistic effects on TRPV1, suppression of cytokines, and anti-inflammatory and antioxidant properties.

Keywords: Antioxidants; Cytokines; Neuropathy; Solanum torvum L.; Solasodine; TRPV.

MeSH terms

  • Animals
  • Constriction
  • Cytokines*
  • Fruit / metabolism
  • Hyperalgesia / complications
  • Hyperalgesia / drug therapy
  • Hyperalgesia / metabolism
  • Interleukin-6
  • Neuralgia* / complications
  • Neuralgia* / drug therapy
  • Neuralgia* / prevention & control
  • Rats
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Cytokines
  • TRPV1 receptor
  • solasodine
  • Tumor Necrosis Factor-alpha
  • Interleukin-6