Trifluoro-Icaritin Ameliorates Neuroinflammation Against Complete Freund's Adjuvant-Induced Microglial Activation by Improving CB2 Receptor-Mediated IL-10/β-endorphin Signaling in the Spinal Cord of Rats.

Autor: Liu G; First Clinical Medical College, Gannan Medical University, Ganzhou, 341000, P. R. China., Jia D; Department of Physiology, School of Basic Medicine Sciences, Gannan Medical University, Ganzhou, 341000, P. R. China., Li W; School of Public Health and Health management, Gannan Medical University, Ganzhou, 341000, P. R. China., Huang Z; Department of Physiology, School of Basic Medicine Sciences, Gannan Medical University, Ganzhou, 341000, P. R. China., Shan R; First Clinical Medical College, Gannan Medical University, Ganzhou, 341000, P. R. China. shanreai@163.com.; Department of Anesthesiology, First Affiliated Hospital of Gannan Medical University, Jiangxi, 341000, P. R. China. shanreai@163.com.; Ganzhou Key Laboratory of Anesthesiology, Ganzhou, 341000, P. R. China. shanreai@163.com., Huang C; Department of Physiology, School of Basic Medicine Sciences, Gannan Medical University, Ganzhou, 341000, P. R. China. huangc6a2013@gmu.edu.cn.; School of Public Health and Health management, Gannan Medical University, Ganzhou, 341000, P. R. China. huangc6a2013@gmu.edu.cn.
Jazyk: angličtina
Zdroj: Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology [J Neuroimmune Pharmacol] 2024 Oct 10; Vol. 19 (1), pp. 53. Date of Electronic Publication: 2024 Oct 10.
DOI: 10.1007/s11481-024-10152-8
Abstrakt: The underlying pathogenesis of chronic inflammatory pain is greatly complex, but the relevant therapies are still unavailable. Development of effective candidates for chronic inflammatory pain is highly urgent. We previously identified that trifluoro-icaritin (ICTF) exhibited a significant therapeutic activity against complete Freund's adjuvant (CFA)-induced chronic inflammatory pain, however, the precise mechanisms remain elusive. Here, the paw withdrawal threshold (PWT), paw withdrawal latency (PWL), and CatWalk gait analysis were used to determine the pain-related behaviors. The expression and co-localization of pain-related signaling molecules were detected by Western blot and immunofluorescence staining. Our results demonstrated that ICTF (3.0 mg/kg, i.p.) effectively attenuated mechanical allodynia, thermal hyperalgesia and improved motor dysfunction induced by CFA, and the molecular docking displayed that CB2 receptor may be the therapeutic target of ICTF. Furthermore, ICTF not only up-regulated the levels of CB2 receptor, IL-10, β-endorphin and CD206, but also reduced the expression of P2Y12 receptor, NLRP3, ASC, Caspase-1, IL-1β, CD11b, and iNOS in the spinal cord of CFA rats. Additionally, the immunofluorescence staining from the spinal cord showed that ICTF significantly increased the co-expression between the microglial marker Iba-1 and CB2 receptor, IL-10, β-endorphin, respectively, but markedly decreased the co-localization between Iba-1 and P2Y12 receptor. Conversely, intrathecal administration of CB2 receptor antagonist AM630 dramatically reversed the inhibitory effects of ICTF on CFA-induced chronic inflammatory pain, leading to a promotion of pain hypersensitivity, abnormal gait parameters, microglial activation, and up-regulation of P2Y12 receptor and NLRP3 inflammasome, as well as the inhibition of CB2 receptor and IL-10/β-endorphin cascade. Taken together, these findings highlighted that ICTF alleviated CFA-induced neuroinflammation by enhancing CB2 receptor-mediated IL-10/β-endorphin signaling and suppressing microglial activation in the spinal cord, and uncovered that CB2 receptor may be exploited as a novel and promising target for ICTF treatment of chronic inflammatory pain.
(© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
Externí odkaz: