Celastrol attenuates chronic constrictive injury-induced neuropathic pain and inhibits the TLR4/NF- κB signaling pathway in the spinal cord

AbstractTripterygium wilfordii Hook F. is a well-known but poisonous traditional Chinese medicine used for treating a wide variety of inflammatory and autoimmune disorders. Celastrol, a quinone methyl triterpenoid compound and a representative component ofT. wilfordii Hook F., shows a variety of pharmacological activities, such as anti-inflammatory and antitumor activities. Here, we investigated the antineuropathic pain (NP) effect of celastrol and its potential mechanisms. Rats with chronic constrictive injury (CCI)-induced NP were used to evaluate the analgesic effect of celastrol. Gabapentin was used as a reference compound (positive control). The results showed that gabapentin (100  mg/kg, i.p.) and multiple doses of celastrol (0.5, 1 and 2 mg/kg, i.p.) increased the threshold of mechanical and thermal pain in the rats with NP. Western blot results showed that celastrol significantly inhibited the activation of microglia and astrocytes in the spinal cord of rats with NP. Add itionally, the levels of the proinflammatory cytokines tumor necrosis factor α (TNF-α), interleukin 1β and interleukin 6, detected by ELISA in the spinal cord of the rats with NP, were significantly inhibited by celastrol. Furthermore, celastrol treatment dramatically inhibited the expression of the TLR4/NF-κB signaling pathway in the spinal cord. Taken together, our findings suggested that celastrol could attenuate mechanical and thermal pain in CCI-induced NP, and this protection might be attr...
Source: Journal of Natural Medicines - Category: Drugs & Pharmacology Source Type: research