Celastrol ameliorates inflammatory pain and modulates HMGB1/NF-κB signaling pathway in dorsal root ganglion. (23rd January 2019)

• Record Type: Journal Article
• Authors: Zhang, Xiumei; Zhao, Wenpin; Liu, Xingfang; Huang, Zhihua; Shan, Reai; Huang, Cheng
• Is Part Of: Neuroscience letters. Volume 692(2019)
• Page Start: 83
• Page End: 89
• Publication Date: 2019-01-23
• Subjects: Chronic inflammatory pain -- Celastrol -- HMGB1 -- NF-κB -- Dorsal root ganglion; Neurology -- Periodicals; Neurology -- Periodicals; Research -- Periodicals; Neurologie -- Périodiques; Neuroanatomie -- Périodiques; Neuropharmacologie -- Périodiques; Neurophysiologie -- Périodiques; Neurology; Periodicals; Electronic journals; 617.48
• DOI: 10.1016/j.neulet.2018.11.002
• Languages: English
• ISSNs: 0304-3940

Abstract

Highlights: Establishing CFA-induced chronic inflammatory pain rat model was to explore the role of neuroinflammation in CFA rats. Celastrol possessing anti-inflammatory activity was further confirmed in DRG of CFA rats. Elucidating the molecular mechanism by which celastrol alleviates CFA-induced inflammatory pain in DRG. Abstract: Evidences reported that high mobility group box 1 (HMGB1) played a pivotal role in the modulation of chronic inflammatory pain. Celastrol, a bioactive component extracted from Tripterygium wilfordii Hook, possesses anti-inflammatory activity, but the underlying mechanism remains to be fully clarified. We aim to investigate whether HMGB1 in dorsal root ganglion (DRG) participates in the effect of celastrol on inflammatory pain. Complete Freund's adjuvant (CFA)-induced inflammatory pain rat model was used. Paw withdrawal latency (PWL) was detected to evaluate the effects of celastrol on CFA-evoked inflammatory pain. After application of celastrol (1mg/kg, i.p.) on day 1, 3, 7 and 14 post-CFA injection, the expression levels of HMGB1, NF-κB, some proinflammatory markers, GFAP and CD11b in DRG were determined by qRT-PCR and western blot analysis. These results showed that celastrol significantly suppressed HMGB1, NF-κB and IL-1β mRNA and protein expression in DRG and alleviated CFA-evoked thermal hyperalgesia. Furthermore, celastrol obviously inhibited COX-2 protein expression and down-regulated IL-6, IL-17, TNF-α, MCP-1, GFAP and CD11b mRNA levels in DRG of CFA rats. Collectively, the present study firstly provide evidences of the anti-inflammatory effect of celastrol via suppressing CFA-induced the activation of HMGB1/NF-κB signaling pathway in DRG, which maybe a potential therapeutic target for celastrol alleviating inflammatory pain.