Translational preclinical evaluation of Strychnos innocua leaf extract: Investigating anti-nociceptive and antidepressant activities using in vivo and in silico models

Abstract

Background: Pain represents a complex physiological response of tissues to injury and often adversely impacts both health and quality of life.  Epidemiological data indicate that virtually all individuals will experience some form of pain during their lifetime. Strychnos innocua (family Loganiaceae) is employed in ethnomedicine for the treatment of inflammation, pain, central nervous system disorders, and various other ailments. This study investigated the antinociceptive and antidepressant effects of S. innocua leaf ethanol extract using established in vivo and in silico models.

Methods: The antinociceptive activity of the extract was evaluated in mice using the acetic acid-induced writhing test, formalin-induced pain, hyperalgesia, and allodynia in carrageenan-induced inflammation. Graded doses of the extract (250 – 1000 mg/kg) were used for these studies. The possible mechanism of action was evaluated by administering the extract in the presence of different antagonists that block antinociception pathways, using the acetic acid-induced writhing model. The tail suspension test was used to evaluate the antidepressant effect of the extract in mice at doses of 250 – 1000 mg/kg in mice. Molecular docking was done using iGemdock.

Results: The extract elicited significant (p < 0.01 – 0.001) reduction in pain behaviors in acetic acid and formalin-induced pain tests. It also showed potent antihyperalgesic and antiallodynic activities in carrageenan-induced inflammation models. Mechanistic studies indicated involvement of ATP-sensitive potassium channels, alpha-2 adrenergic receptors, and adenosine receptors in the extract’s antinociceptive effects. Molecular docking supported these findings, identifying bioactive compounds such as 9,12,15-octadecatrienoic acid and n-hexadecanoic acid as the major culprits. The extract also demonstrated significant antidepressant effects, which were further supported by docking interactions with serotonin and dopamine transporters.

Conclusion: The study outcome shows that the extract has potent antinociceptive and antidepressant properties that may be mediated through multiple pathways.

 

Keywords: Antinociceptive; hyperalgesia; allodynia; antidepressant; in silico; in vivo.