San Pian decoction can treat nitroglycerin-induced migraine in rats by inhibiting the PI3K/AKT and MAPK signaling pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: San Pian decoction (SPD), a traditional Chinese medicine preparation composed of eight herbs, has been reported to alleviate migraine. However, its active ingredients and the potential mechanism of action remains unclear. The purpose of this study was to comprehensively analyze SPD for the treatment of chronic migraine based on pharmacological direction and to identify the active ingredients and pharmacological mechanism of SPD in the treatment of migraine. MATERIALS AND METHODS: The active components in SPD were identified by AB SCIEX quadrupole time-of-flight mass spectrometer, and the prediction targets and pharmacological networks related to migraine were constructed. The mechanism of SPD in treating migraine was studied through network pharmacology, which was further verified using pharmacological experiments. RESULTS: A total of 489 targets of 26 compounds were identified. Based on Venn analysis, we found 117 intersection targets between SPD and migraine, that is, these targets were related to the treatment of migraine. Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that the treatment of migraine using SPD was related to the PI3K/AKT and MAPK signaling pathways. The effect of SPD on migraine was verified by measuring the levels of the inflammatory factors, nitric oxide (NO), interleukin (IL-6), endothelin (ET),5-hydroxytryptamine(5-HT), indoleamine 2,3-dioxygenas (IDO), tumor necrosis factor (TNF-α) and calcitonin gene-related peptide (CGRP). Lastly, real-time polymerase chain reaction and western blotting were used to verify gene and protein expression in the PI3K/AKT and MAPK signaling pathways. Expression of the genes P38, JNK, ERK, PI3K and AKT, and the protein expression of p-P38, p-JNK, p-ERK, p-AKT and p-PI3K were significantly downregulated. Our findings indicated that SPD could prevent inflammation by regulating the inflammatory cytokines and key genes and proteins in the PI3K/AKT and MAPK signaling pathways to treat migraine. CONCLUSION: Our findings reveal that SPD could treat nitroglycerin-induced migraine by regulating p-AKT, p-pI3k, p-p38, p-ERK, p-JNK, IL-6, and TNF-α inflammatory factors in the PI3K/AKT and MAPK signaling pathways.

Proteomics and metabolomics analyses reveal the full spectrum of inflammatory and lipid metabolic abnormalities in dyslipidemia.

Dyslipidemia is a common, chronic metabolic disease associated with cardiovascular complications. Due to the multiplicity of etiological factors, the pathogenesis of dyslipidemia is still unclear. In this study, we combined proteomics and metabolomics methods to analyze the plasma of patients with dyslipidemia and healthy subjects. isobaric tags for relative and absolute quantification (iTRAQ) markers, combined with LC-MS/MS proteomics technology and the UHPLC/Orbitfast-X Tribrid system, were used to establish the metabolite profile in clinical dyslipidemia. A total of 137 differentially expressed proteins, mainly related to biological processes such as protein activation cascades, adaptive immune responses, complement activation, acute inflammatory responses, and regulation of acute inflammatory responses, were identified. These proteins are involved in the regulation of important metabolic pathways, such as immunity and inflammation, coagulation and hemostasis, lipid metabolism, and oxidation and antioxidant defenses. The analysis of clinical metabolites showed there were 69 different metabolites in plasma, mainly related to glycerolipid, sphingolipid, porphyrin, α-linolenic acid, linoleic acid, and arachidonic acid metabolism, suggesting that the regulation of inflammation and lipid metabolism may be disturbed in patients with dyslipidemia. Among these, significant changes were observed in indole-3-propionic acid (IPA), which is considered as a potential biomarker of dyslipidemia. The combined analysis of proteins and metabolites showed that arachidonic acid, linoleic acid, and lipid metabolic pathways were closely related to dyslipidemia. IPA may be a potential biomarker. The information provided in this study may provide new insights into the pathogenesis of animal models of dyslipidemia and related disease models, as well as potential intervention targets.