wogonin and gamma-sitosterol

BACKGROUND Heat-clearing and detoxifying herbs (HDHs) play an important role in the prevention and treatment of coronavirus infection. However, their mechanism of action needs further study. This study aimed to explore the anti-coronavirus basis and mechanism of HDHs. MATERIAL AND METHODS Database mining was performed on 7 HDHs. Core ingredients and targets were screened according to ADME rules combined with Neighborhood, Co-occurrence, Co-expression, and other algorithms. GO enrichment and KEGG pathway analyses were performed using the R language. Finally, high-throughput molecular docking was used for verification. RESULTS HDHs mainly acts on NOS3, EGFR, IL-6, MAPK8, PTGS2, MAPK14, NFKB1, and CASP3 through quercetin, luteolin, wogonin, indirubin alkaloids, ß-sitosterol, and isolariciresinol. These targets are mainly involved in the regulation of biological processes such as inflammation, activation of MAPK activity, and positive regulation of NF-kappaB transcription factor activity. Pathway analysis further revealed that the pathways regulated by these targets mainly include: signaling pathways related to viral and bacterial infections such as tuberculosis, influenza A, Ras signaling pathways; inflammation-related pathways such as the TLR, TNF, MAPK, and HIF-1 signaling pathways; and immune-related pathways such as NOD receptor signaling pathways. These pathways play a synergistic role in inhibiting lung inflammation and regulating immunity and antiviral activity. CONCLUSIONS HDHs play a role in the treatment of coronavirus infection by regulating the body's immunity, fighting inflammation, and antiviral activities, suggesting a molecular basis and new strategies for the treatment of COVID-19 and a foundation for the screening of new antiviral drugs.

Topics: Alkaloids; Caspase 3; Coronavirus; Coronavirus Infections; COVID-19 Drug Treatment; Cyclooxygenase 2; Databases, Pharmaceutical; Drugs, Chinese Herbal; Flavanones; Humans; Indoles; Interleukin-6; Lignin; Luteolin; Mitogen-Activated Protein Kinase 14; Mitogen-Activated Protein Kinase 8; Molecular Docking Simulation; Naphthols; NF-kappa B p50 Subunit; Nitric Oxide Synthase Type III; Protein Interaction Maps; Quercetin; SARS-CoV-2; Signal Transduction; Sitosterols; Transcriptome

To explore the molecular mechanism of Simiao powder in the treatment of knee osteoarthritis.. Based on oral bioavailability and drug-likeness, the main active components of Simiao powder were screened using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). GeneCard, OMIM, DisGeNET, DrugBank, PharmGkb, and the Therapeutic Target Database were used to establish target databases for knee osteoarthritis. Cytoscape software was used to construct a visual interactive network diagram of "active ingredient - action target - disease." The STRING database was used to construct a protein interaction network and analyze related protein interaction relationships. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) biological process enrichment analysis were performed on the core targets. Additionally, Discovery Studio software was used for molecular docking verification of active pharmaceutical ingredients and disease targets.. Thirty-seven active components of Simiao powder were screened, including 106 common targets. The results of network analysis showed that the targets were mainly involved in regulating biological processes such as cell metabolism and apoptosis. Simiao powder components were predicted to exert their therapeutic effect on the AGE-RAGE signaling pathway in diabetic complications, IL-17 signaling pathway, TNF signaling pathway, Toll-like receptor signaling pathway, and HIF-1 signaling pathway. The molecular docking results showed that the active components of Simiao powder had a good match with the targets of IL1B, MMP9, CXCL8, MAPK8, JUN, IL6, MAPK1, EGF, VEGFA, AKT1, and PTGS2.. Simiao powder has multisystem, multicomponent, and multitarget characteristics in treating knee osteoarthritis. Its possible mechanism of action includes inhibiting the inflammatory response, regulating immune function, and resisting oxidative stress to control the occurrence and development of the disease. Quercetin, wogonin, kaempferol, beta-sitosterol, and other active ingredients may be the material basis for the treatment of knee osteoarthritis.

Topics: Administration, Oral; Apoptosis; Drugs, Chinese Herbal; Flavanones; Humans; Inflammation; Kaempferols; Medicine, Chinese Traditional; Molecular Docking Simulation; Osteoarthritis, Knee; Oxidative Stress; Powders; Quercetin; Reproducibility of Results; Signal Transduction; Sitosterols; Software