Network Pharmacology and Molecular Docking to Elucidate the Potential Mechanism of Ligusticum Chuanxiong Against Osteoarthritis. Frontiers in pharmacology Osteoarthritis (OA) is a degenerative disease which serious affects patients. Ligusticum chuanxiong (CX) has been shown to have a certain curative effect on osteoarthritis in traditional Chinese medicine therapy. This study is based on network pharmacology and molecular docking technology to explore the potential mechanism of CX. Components of CX to treat osteoarthritis were screened in the TCMSP database and targets were predicted by the PharmMapper database, the osteoarthritis targets were collected from the GeneCards database, and intersection genes were found to be the possible targets of CX anti-OA. The STRING database and Cytoscape software were utilized for protein-protein interaction analysis and further screening of core targets. The Metascape database was used for KEGG and GO enrichment analyses. Then, the top 10 pathways were selected to construct "drug-compound-target-pathway-disease" network analysis. Finally, molecular docking was used to analyze the binding affinity of seven compounds with core targets and TNF-α. Seven compounds with 253 non-repetitive targets of CX were screened from the TCMSP database and 60 potential intersection targets of CX anti-OA were found. PPI network analysis showed that the core targets were ALB, AKT1, IGF1, CASP3, MAPK1, ANXA5, and MAPK14, while GO and KEGG pathway enrichment analyses showed that the relevant biological processes involved in the treatment of osteoarthritis by CX might include the MAPK cascade and reactive oxygen species metabolic process. The KEGG pathway analysis result was mainly associated with the MAPK signaling pathway and PI3K-AKT signaling pathway. We further docked seven ingredients with MAPK1 and MAPK14 enriched in the MAPK pathway, and TNF-α as the typical inflammatory cytokine. The results also showed good binding affinity, especially FA, which may be the most important component of CX anti-OA. Our research revealed the potential mechanism of CX in the treatment of OA, and our findings can also pave the way for subsequent basic experimental verification and a new research direction. 10.3389/fphar.2022.854215

Potential Mechanisms of Guizhi Fuling Wan in Treating Endometriosis: An Analysis Based on TCMSP and DisGeNET Databases. Journal of ethnopharmacology ETHNOPHARMACOLOGICAL RELEVANCE:Guizhi Fuling Wan (GFW), is a traditional Chinese herbal formula that consists of Cinnamomi Ramulus (Guizhi), Poria Cocos(Schw.) Wolf. (Fuling), Persicae Semen (Taoren), Radix Paeoniae Rubra (Chishao), and Cortex Moutan (Mudanpi). This formula has been used in traditional Chinese medicine for more than 1800 years to treat disorders caused by stagnation of circulation and qi (air). AIM OF THE STUDY:Based on pre-clinical and clinical studies, this review aimed to reveal the potential mechanisms of GFW in inhibiting endometriosis. The enhancement of therapeutic effects of western medications on endometriosis by GFW was also shown. MATERIALS AND METHODS:A bibliographic assessment of publications on "Guizhi Fuling Wan" and "endometriosis" indexed in PubMed, Science Direct, and China National Knowledge Infrastructure (CNKI) was conducted. Five pre-clinical studies and 13 clinical studies were selected for this review. Moreover, the targeted molecules of each herb were first extracted from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) Database and Analysis Platform followed by obtaining the endometriosis-related genes from DisGeNET. Subsequently, pathway and gene ontology analyses using David Bioinformatics Resources explored the potential mechanisms of therapeutic effects of GFW in treating endometriosis. RESULTS:Pre-clinical and clinical studies showed that GFW might inhibit the growth of endometriotic lesion through the modulation of immunity, apoptosis-regulating molecules, and angiogenesis-associated factors, while enhancing the therapeutic effects of western medications in treating endometriosis. Furthermore, pathway and gene ontology analyses demonstrated that GFW might attenuate the disease primarily by affecting AGE-RAGE signaling pathway in diabetic complications (hsa04933) as well as pathways involved in Kaposi sarcoma-associated herpesvirus infection (hsa05167), human cytomegalovirus infection (has05163), and fluid shear stress and atherosclerosis (hsa05418). These pathways were all involved in the regulation of inflammation, angiogenesis, and apoptosis and commonly affected by all herbs. CONCLUSIONS:The current review revealed that endometriosis is highly associated with aberrant inflammatory, angiogenic, and apoptotic activities. The therapeutic effects of GFW on endometriosis are likely to act through regulating these activities. 10.1016/j.jep.2024.118190

Exploring the efficacious constituents and underlying mechanisms of sini decoction for sepsis treatment through network pharmacology and multi-omics. Phytomedicine : international journal of phytotherapy and phytopharmacology BACKGROUND:Traditional Chinese medicine prescription sini decoction (SND) can alleviate inflammation, improve microcirculation, and modulate immune status in sepsis patients. However, its underlying mechanisms remain unclear, and therapeutic effects may vary among individuals. PURPOSE:Through a comprehensive and systematic network pharmacology analysis, the purpose of this study is to investigate the therapeutic mechanisms of SND in treating sepsis. METHODS:An analysis of WGCNA identified CX3CR1 as a key gene influencing sepsis prognosis. A drug-active component-target network for SND was created using the traditional Chinese medicine systems pharmacology (TCMSP) database and Cytoscape software. Shared targets between SND and CX3CR1 high-expression gene modules were found through the GEO database. Gene module functionality was analyzed using GO, KEGG, GSEA, and GSVA. Unsupervised clustering of sepsis patients was performed based on the ferroptosis gene set, and immune cell interactions and mechanisms were explored using CIBERSORT, single-cell sequencing, and intercellular communication analysis. RESULTS:This study demonstrates that high expression of CX3CR1 improves survival rates in sepsis patients and is associated with immune cell signaling pathways. SND contains 116 active components involved in oxidative stress and lipid metabolism pathways. HMOX1, a co-expressed gene in SND and CX3CR1 high-expression gene module, plays a crucial role in sepsis survival. Unsupervised clustering analysis classified sepsis patients into three clusters based on the ferroptosis gene set, revealing differences in immune cell expression and involvement in heme metabolism pathways. Notably, intercellular interactions among immune cells primarily occur through paracrine and autocrine mechanisms in MIF, GALECTIN, and IL16 signaling pathways, modulating the immune-inflammatory microenvironment in sepsis. CONCLUSIONS:This study identifies CX3CR1 as a crucial molecule impacting sepsis prognosis through WGCNA analysis. It reveals that SND's active component, quercetin and kaempferol, target HMOX1 via related pathways to regulate heme metabolism, reduce inflammation, inhibit ferroptosis, and improve immune function, ultimately improving sepsis prognosis. These findings offer a solid pharmacological foundation and potential therapeutic targets for SND in treating sepsis. 10.1016/j.phymed.2023.155212

TCMSP: a database of systems pharmacology for drug discovery from herbal medicines. Ru Jinlong,Li Peng,Wang Jinan,Zhou Wei,Li Bohui,Huang Chao,Li Pidong,Guo Zihu,Tao Weiyang,Yang Yinfeng,Xu Xue,Li Yan,Wang Yonghua,Yang Ling Journal of cheminformatics BACKGROUND:Modern medicine often clashes with traditional medicine such as Chinese herbal medicine because of the little understanding of the underlying mechanisms of action of the herbs. In an effort to promote integration of both sides and to accelerate the drug discovery from herbal medicines, an efficient systems pharmacology platform that represents ideal information convergence of pharmacochemistry, ADME properties, drug-likeness, drug targets, associated diseases and interaction networks, are urgently needed. DESCRIPTION:The traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP) was built based on the framework of systems pharmacology for herbal medicines. It consists of all the 499 Chinese herbs registered in the Chinese pharmacopoeia with 29,384 ingredients, 3,311 targets and 837 associated diseases. Twelve important ADME-related properties like human oral bioavailability, half-life, drug-likeness, Caco-2 permeability, blood-brain barrier and Lipinski's rule of five are provided for drug screening and evaluation. TCMSP also provides drug targets and diseases of each active compound, which can automatically establish the compound-target and target-disease networks that let users view and analyze the drug action mechanisms. It is designed to fuel the development of herbal medicines and to promote integration of modern medicine and traditional medicine for drug discovery and development. CONCLUSIONS:The particular strengths of TCMSP are the composition of the large number of herbal entries, and the ability to identify drug-target networks and drug-disease networks, which will help revealing the mechanisms of action of Chinese herbs, uncovering the nature of TCM theory and developing new herb-oriented drugs. TCMSP is freely available at http://sm.nwsuaf.edu.cn/lsp/tcmsp.php. 10.1186/1758-2946-6-13