Clarifying the mechanism of Curcumin in the treatment of neuropathic pain based on network pharmacology and molecular docking technology.

Abstract

This study aims to identify the primary targets of Curcumin in neuropathic pain and clarify the underlying mechanisms involved. Network pharmacology and bioinformatics are used to explore the potential targets and biological functions of Curcumin in the treatment of neuropathic pain. The model of chronic neuropathic pain was established by ligation of the unilateral sciatic nerve to investigate the effect of Curcumin on neuropathic pain in rats. Paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) measured by thermal stimulation were tested. H&E and TUNEL were used to detect tissue injury and apoptosis, respectively. Apoptosis-related proteins (caspase3, caspase9, cleaved-caspase3, cleaved-caspase9, Bax, Bcl-2) were detected by western blot. ELISA was used to detect the levels of inflammatory factors (IL-6, IL-10, TNF-α, and IL-1β) and oxidative stress indicators (ROS, SOD, and GSH-PX) in blood samples. The expression of core genes and proteins obtained from network pharmacology analysis was detected using RT-PCR and western blot, respectively. A total of 56 Curcumin-related targets were obtained. After intervention with Curcumin, the neuropathic pain symptoms can be significantly alleviated. The tissue damage and apoptosis were significantly inhibited. Curcumin could regulate the levels of inflammatory factors (IL-6, IL-10, TNF-α, and IL-1β) and oxidative stress indicators (ROS, SOD, and GSH-PX). The expressions of core genes and proteins (CCL-5, CXCR2, (P-)JAK2, (P-)STAT3, SRC, (P-)PI3K, (P-)AKT, HIF-1α, and NF-κB) were also adjusted by Curcumin. Curcumin exhibited biological functions of anti-apoptosis, anti-inflammation, and anti-oxidant stress against neuropathic pain. Curcumin can serve as a potential natural product for the treatment of neuropathic pain in the clinical setting.