Effect of Jiawei Tongqiao Huoxue decoction in basilar artery dolichoectasia mice through yes-associated protein/transcriptional co-activator with PDZ-binding motif pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: The Jiawei Tongqiao Huoxue decoction (JTHD), composed of Acorus calamus var. angustatus Besser, Paeonia lactiflora Pall., Conioselinum anthriscoides 'Chuanxiong', Prunus persica (L.) Batsch, Ziziphus jujuba Mill., Carthamus tinctorius L., Pueraria montana var. lobata (Willd.) Maesen & S.M.Almeida ex Sanjappa & Predeep, Zingiber officinale Roscoe, Leiurus quinquestriatus, and Moschus berezovskii Flerov, was developed based on Tongqiao Huoxue decoction in Wang Qingren's "Yilin Gaicuo" in the Qing Dynasty. It has the effect of improving not only the blood flow velocity of vertebral and basilar arteries but also the blood flow parameters and wall shear stress. Especially in recent years, the potential efficacy of traditional Chinese medicine (TCM) for the treatment of basilar artery dolichoectasia (BAD) has attracted great attention as there are still no specific remedies for this disease. However, its molecular mechanism has not been elucidated. To identify the potential mechanisms of JTHD will help to intervene BAD and provide a reference for its clinical application. AIM OF THE STUDY: This study aims to establish a mouse model of BAD and explore the mechanism of JTHD regulating yes-associated protein/transcriptional co-activator with PDZ-binding motif (YAP/TAZ) pathway for attenuating BAD mice development. MATERIALS AND METHODS: Sixty post-modeling C57/BL6 female mice were randomly divided into sham-operated, model, atorvastatin calcium tablet, low-dose JTHD, and high-dose JTHD groups. After 14 days of modeling, the pharmacological intervention was given for 2 months. Then, JTHD was analyzed by liquid chromatography-tandem mass spectrometry (LC-MS). ELISA was utilized to detect the changes in vascular endothelial growth factor (VEGF) and lipoprotein a (Lp-a) in serum. EVG staining was conducted to observe the pathological changes of blood vessels. TUNEL method was employed to detect the apoptosis rate of vascular smooth muscle cells (VSMCs). Micro-CT and ImagePro Plus software were used to observe and calculate the tortuosity index, lengthening index, percentage increase in vessel diameter, and tortuosity of the basilar artery vessels in mice. Western blot analysis was performed to detect the expression levels of YAP and TAZ proteins in the vascular tissues of mice. RESULTS: Many effective compounds such as choline, tryptophan, and leucine with anti-inflammation and vascular remodeling were identified in the Chinese medicine formula by LC-MS analysis. The serum levels of VEGF in the model mice decreased significantly while the levels of Lp-a increased obviously compared with those in the sham-operated group. The intima-media of the basilar artery wall showed severe disruption of the internal elastic layer, atrophy of the muscular layer, and hyaline changes of the connective tissue. Apoptosis of VSMCs added. Dilatation, elongation, and tortuosity of the basilar artery became notable, and tortuosity index, lengthening index, percentage increase in vessel diameter, and bending angle remarkably improved. The expression levels of YAP and TAZ protein in blood vessels elevated conspicuously (P < 0.05, P < 0.01). JTHD group markedly reduced the lengthening, bending angle, percentage increase in vessel diameter, and tortuosity index of basilar artery compared with the model group after 2 months of pharmacological intervention. The group also decreased the secretion of Lp-a and increased the content of VEGF. It inhibited the destruction of the internal elastic layer, muscular atrophy, and hyaline degeneration of connective tissue in basilar artery wall. The apoptosis of VSMCs was decreased, and the expression levels of YAP and TAZ proteins were abated (P < 0.05, P < 0.01). CONCLUSIONS: The mechanism of inhibition of basilar artery elongation, dilation, and tortuosity by JTHD, which has various anti-BAD effective compound components, may be related to the reduction in VSMCs apoptosis and downregulation of YAP/TAZ pathway expression.

[Analysis of Wumei Pills in treating chronic digestive system diseases with concept of "treating different diseases with same method" based on network pharmacology and molecular docking].

The present study explored the material basis and underlying mechanism of Wumei Pills in the treatment of ulcerative colitis(UC), diabetic enteropathy(DE), and irritable bowel syndrome(IBS) based on network pharmacology and molecular docking.The active components and targets of Wumei Pills were obtained and screened out from TCMSP, and the target names were standardized by UniProt.The related targets of UC, DE, and IBS were searched from GeneCards, DisGeNET, DrugBank, and OMIM.The Venn dia-gram was constructed using the Venny 2.1 online analysis tool to obtain the common targets of the drug and diseases.The "drug-active ingredient-target" network was constructed by Cytoscape 3.7.2.Gene Ontology(GO) function enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses of common targets were carried out by DAVID.The main active components and targets were docked by AutoDock.The therapeutic mechanism of Wumei Pills was presumedly related to the regulation of the cancer pathway, TNF signaling pathway, HIF-1 signaling pathway, PI3 K-Akt signaling pathway, NF-κB signaling pathway, Toll-like receptor signaling pathway, JAK-STAT signaling pathway, etc.The results of molecular docking showed that the main active components could bind to the core targets, possessing stable conformation.The therapeutic effects of Wumei Pills against three diseases involved a variety of compounds such as flavonoids, sterols, and alkaloids in the prescriptions, which acted on key targets through multiple organs and participated in multiple signaling pathways such as apoptosis and immune inflammation, thereby exerting the therapeutic action on different diseases with the same method.This study explained the underlying mechanism of Wumei Pills in "treating different diseases with same method", and is expected to provide a theoretical basis for further understanding the mechanism of Wumei Pills and exploring the new clinical application.