Ruan, Yonglan; Ling, Jinying; Ye, Fan; Cheng, Nuo; Wu, Fei; Tang, Zongxiang; Cheng, Xiaolan; Liu, Hongquan published the artcile< Paeoniflorin alleviates CFA-induced inflammatory pain by inhibiting TRPV1 and succinate/SUCNR1-HIF-1α/NLPR3 pathway>, Product Details of C19H34O2, the main research area is paeoniflorin SUCNR TRPV HIF NLRP CFA inflammatory pain signaling; Inflammatory pain; NLPR3; Paeoniflorin; SUCNR1; Succinate; TRPV1.
Treatment of chronic inflammatory pain remains a major goal in the clinic. It is thus of prime importance to characterize inherent pathophysiol. pathways to design new therapeutic strategies and analgesics for pain management. Paeoniflorin (PF), a monoterpenoid glycoside from Paeonia lactiflora Pallas plants, possesses promising anti-nociceptive property. However, therapeutic effect and underlying mechanism of action of PF on inflammatory pain have not yet been fully elucidated. In this study, we aim to investigate the analgesic effect further and clarify its mechanism of action of PF on complete freund’s adjuvant (CFA)-evoked inflammatory pain. Twenty-four male mice were divided into 3 groups: sham, CFA, and CFA + PF groups (n = 8/group). Mice were treated with normal saline or PF (30 mg/kg) for 11 days. Footpad swelling (n = 8/group), mech. (n = 8/group) and thermal hypersensitivity (n = 8/group) were measured to evaluate the analgesic effect of PF on CFA-injected mice. At the end of the animal experiment, blood and L4-L6 dorsal root ganglion neurons were collected to assess the therapeutic effect of PF on CFA-induced inflammatory pain. Next, hematoxylin and eosin, quant. realtime PCR, ELISA, capsaicin and di-Me succinate induced pain test (n = 8/group), motor coordination test (n = 8/group), tail flicking test (n = 8/group), pyruvate and succinate dehydrogenase assay (n = 6/group), immunohistochem. staining, were performed to clarify the action mechanism of PF on CFA-evoked inflammatory pain. Besides, the effect of PF on TRPV1 was evaluated by whole-cell patch clamp recording on primary neurons (n = 7). Finally, mol. docking further performed to evaluate the binding ability of PF to TRPV1. PF significantly relieved inflammatory pain (P < 0.001) and paw edema (P < 0.001) on a complete Freund adjuvant (CFA)-induced peripheral inflammatory pain model. Furthermore, PF inhibited neutrophil infiltration (P < 0.01), IL-1β increase (P< 0.01), and pain-related peptide substance P release (P < 0.001). Intriguingly, CFA-induced succinate aggregation was notably reversed by PF via modulating pyruvate and SDH activity (P < 0.01). In addition, PF dampened the high expression of subsequent succinate receptor SUCNR1 (P < 0.01), HIF-1α(P < 0.05), as well as the activation of NLRP3 inflammasome (P < 0.05) and TRPV1 (P < 0.05). More importantly, both capsaicin and di-Me succinate supplementation obviously counteracted the pain-relieving effect of PF and TRPV1 (P < 0.01 or P < 0.001). Our findings suggest that PF can significantly relieve CFA-induced paw swelling, as well as mech. and thermal hyperalgesia. PF alleviated inflammatory pain partly through inhibiting the activation of TRPV1 and succinate/SUCNR1-HIF-1α/NLRP3 pathway. Furthermore, we found that PF exerted its analgesic effect without affecting motor coordination and pain-related cold ion-channels. In summary, this study may provide valuable evidence for the potential application of PF as therapeutic strategy for inflammatory pain treatment. International Immunopharmacology published new progress about Analgesia. 112-63-0 belongs to class esters-buliding-blocks, and the molecular formula is C19H34O2, Product Details of C19H34O2.
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