Xiongshao Zhitong granules alleviate nitroglycerin-induced migraine by regulating the TRPV1-mediated NLRP3 inflammatory pathway in rats
Abstract
BACKGROUND: Migraine is a prevalent neurological disorder accompanied by a considerable economic burden. Xiongshao Zhitong granules (XSZT) have anti-inflammatory and analgesic functions in the clinic and are used for migraine therapy. However, the mechanisms by which XSZT treats migraine remain unclear.
PURPOSE: To discover the underlying mechanism and active ingredients of XSZT in the treatment of migraine.
METHODS: The nitroglycerin (NTG)-induced chronic migraine (CM) model was established and used to detect the therapeutic effect of XSZT on migraine. To elucidate the mechanism, we detected transient receptor potential vanilloid 1 (TRPV1) -mediated NOD-like receptor protein 3 (NLRP3) inflammasome activation in the CM rat model and the LPS-induced inflammatory BV-2 cell model using Western blotting, immunofluorescence and ELISA techniques. The potentially active ingredients of XSZT were determined by UHPLC-LTQ-Orbitrap MS, molecular docking, and surface plasmon resonance.
RESULTS: Our findings revealed that XSZT reduced the number of head scratching, increased the periorbital pain threshold and shortened the time spent in the dark box, decreased c-Fos expression in the CM rat model, suggesting an analgesic effect of XSZT on migraine. XSZT inhibited neurogenic inflammation, including downregulating CGRP, TNF-α, IL-1β and IL-18 levels and decreasing the degranulation rate of mast cells. Additionally, XSZT suppressed the expression and activation of TRPV1 and the NLRP3…
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