Essential oil from Chrysanthemi Flos alleviates the nitroglycerin-induced migraine in mice by regulating the vasoactive substances and the PI3K/AKT signal pathway.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE: Chrysanthemi Flos, the flowers of Chrysanthemum morifolium Ramat., is used to treat the headache and vertigo. However, the therapeutic effect and the potential mechanisms of the essential oil from Chrysanthemi Flos (EOCF) against migraine remain unknown. AIM OF THE STUDY: The purpose of this research is to investigate the pharmacological properties and the molecular mechanisms of EOCF. MATERIALS AND METHODS: The chemical components of EOCF were identified by GC-MS and NMR techniques. The anti-neuroinflammatory effect was examined based on the LPS-stimulated BV2 cell model using the Griess and ELISA methods. A nitroglycerin-induced migraine model and an acetic acid-stimulated writhing test in mice were used to assess the anti-migraine and analgesic effects, respectively. Network pharmacology, molecular docking, ELISA and western blotting were utilized to mechanistic analysis perform. RESULTS: 32 compounds were identified tentatively by GC-MS, and 4 compounds were isolated and structurally elucidated through HPLC and NMR methods, respectively. The results of cell experiments revealed that EOCF significantly inhibited the nitric oxide (NO) production with the ICvalue of 29.75 μg/mL and the levels of TNF-α and IL-6 in BV2 cells stimulated by LPS. In the nitroglycerin-induced migraine mice, EOCF treatment significantly reduced the migraine-like head scratching, the serum levels of CGRP and ET-1, and the brain level of CRLR, while increased the levels of 5-HT and 5-HT1B in brain tissues. Molecular docking indicated strong binding affinity between the ingredients of EOCF and 5-HT1B. Network pharmacology results and western blotting validation indicated that EOCF prominently suppressed the PI3K-AKT pathway. Furthermore, EOCF also displayed the analgesic effect by decreasing the number of writhing and the serum levels of PGE2 and CGRP in the acetic acid-induced writhing model mice. CONCLUSIONS: This research disclosed that EOCF ameliorated migraine by regulating the vasoactive substances and the PI3K/AKT signal pathway. The study supported the traditional use of Chrysanthemi Flos for remedying headache.