Discovery of tetrahydropalmatine and protopine regulate the expression of dopamine receptor D2 to alleviate migraine from Yuanhu Zhitong formula
Abstract
BACKGROUND: Migraine is the third most common disease worldwide, leading to severely decreased quality of life for the patients. In spite of great efforts endeavored in pharmacological and nonpharmacological therapeutic strategies for treating migraine, the outcome is rather disappointing in terms of efficacy. Compelling evidence shows that the expression level of dopamine receptor D2 (DRD2) plays an essential role in progression of migraine.
PURPOSE: To explore potential therapeutical possibilities, the attention was paid to Yuanhu Zhitong formula (YHZTF), which is a classical traditional Chinese medicine prescription frequently applied to relieve pain. The aim of this study was to identify the promising compounds derived from YHZTF with anti-migraine effects and investigate the underlying molecular mechanism.
METHODS: The high-resolution mass spectrometry and molecular networking were performed for comprehensive chemical profiling of YHZTF. Network pharmacology was used to generate herbal-component-target-pathway network. Based on the pathway enrichment analysis, the active substances of anti-migraine and the potential molecular mechanism were further determined by performing animal experiments combined with molecular docking strategy.
RESULTS: In total, 31 substances were identified in YHZTF, including alkaloids such as tetrahydropalmatine and protopine. The analysis of herbal-component-target-pathway network suggests that the alkaloid substances (e.g. tetrahydropalmatine…
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