Diosmin Alleviates Pain via Mechanisms Involving Acetylcholinesterase and TRPV1 Inhibition: An In Silico and In Vivo Study.

Abstract

BACKGROUND: Diosmin, a flavonoid glycoside with reported anti-inflammatory effects, was evaluated for its potential analgesic activity using in vivo and in silico studies. METHODS: The antinociceptive effect of diosmin was evaluated in mice using capsaicin- and formalin-induced paw-licking tests as well as hot plate and tail flick assays. Target prediction using Similarity Ensemble Approach (SEA) and molecular docking were conducted to validate diosmin's interaction with Transient Receptor Potential Vanilloid 1 (TRPV1) and acetylcholinesterase (AChE) in silico. FINDINGS: Diosmin (60 and 30 mg/kg) significantly reduced pain behaviour by 90.8% and 83.2%, respectively, in the capsaicin-induced paw-licking test, while BCTC, a TRPV1 antagonist, significantly blocked diosmin action. In the formalin test, atropine significantly blocked the action of diosmin at the early phase. Diosmin at 60 mg/kg increased hot plate latency by 104.8%. In the tail flick test, diosmin at 60 and 30 mg/kg increased latency by 103.7% and 90.6%, respectively, indicating central analgesic effects. No significant alterations in body temperature were observed. Docking studies confirmed diosmin's favourable binding to the active site of AChE with a binding energy of -9.77 kcal/mol. Diosmin engages the TRPV1 vanilloid pocket mainly through hydrophobic interactions. CONCLUSION: Diosmin exerts central and peripheral antinociceptive effects mediated, at least partially, through TRPV1 antagonism and cholinergic pathways.