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Use network pharmacology combined with molecular docking to study the effects of Simiao-Yongan Decoction (SMYAD) intervenes in Knee Osteoarthritis (KOA) related targets and signaling pathways, and explores the molecular mechanism of SMYAD in treating KOA. The active ingredients and targets of SMYAD, which concluded 4 traditional Chinese medicines, were screened in TCMSP, and the related gene targets of KOA were screened in the disease databases GeneCards, MalaCards, DisGeNET, and Comparative Toxicogenomics Database, and their intersection data were obtained after integration. And used Cytoscape 3.9.1, the software topologies the network diagram of "compound-drug-active ingredient-target protein-disease." Obtains the protein-protein interaction network diagram through STRING, and enriches and analyzes the obtained core targets. Carry out molecular docking matching verification on the main active ingredients and key targets of the drug. 106 active ingredients and 175 targets were screened from SMYAD to intervene in KOA, 36 core targets were obtained through protein-protein interaction screening, and 10 key targets played an important role. The enrichment results showed that the biological process of gene ontology mainly involved positive regulation of gene expression, negative regulation of apoptosis process, and positive regulation of apoptosis process. KEGG signaling pathway mainly involves AGE-RAGE signaling pathway in diabetic complications, TNF signaling pathway, hypoxia-inducible factor-1 signaling pathway, IL-17 signaling pathway. The pathway of Reactome mainly involves interleukin-4 and interleukin-13 signaling, cytokine signaling in immune system, immune system, apoptosis. Molecular docking showed that the mainly effective components of SMYAD can fully combine with TNF, IL1B, IL6, and CASP3. The results show that the main active ingredients and potential mechanism of action of SMYAD in the treatment of KOA have the characteristics of multiple targets and multiple pathways, which provides ideas and basis for further in-depth exploration of its specific mechanism., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Pulmonary arterial hypertension (PAH) is a progressive and malignant disease characterized by pulmonary small arteries and right ventricle (RV) remodeling that can lead to severe RV dysfunction and death. The current therapeutic targets for RV dysfunction, which is strongly linked to mortality, are far from adequate. Therefore, we investigated the effect of ursolic acid (UA), a pentacyclic triterpenoid carboxylic acid, on PAH-induced RV remodeling and its underlying mechanism. We established a PAH model by injecting Sprague Dawley rats with monocrotaline (MCT, 60 mg/kg, ip), as verified by echocardiography and hemodynamic examination. Proteomic analysis was performed on RV samples using a Q Exactive high-field mass spectrometer, followed by KEGG enrichment analysis. The effect of 4 weeks of UA (50 mg/kg) treatment on RV remodeling was explored based on ultrasound, hemodynamic parameters, and histological changes, with the mechanism verified in vivo and in vitro by qRT-PCR and western blotting. RV hypertrophy, fibrosis, increased apoptosis, and abnormal metabolism were induced by MCT and suppressed by UA via a mechanism that changed the expression of key markers. UA also attenuated the Phenylephrine-induced hypertrophy of neonatal rat ventricular myocytes and upregulated peroxisome proliferator-activated receptor-alpha (PPARα), a key fatty acid metabolism regulator, and its downstream factor carnitine palmitoyl transferase 1b. In conclusion, UA exerts beneficial effects on PAH-induced RV dysfunction and remodeling by regulating PPARα-dependent fatty acid metabolism.