Combinatorial chemistry & high throughput screening最新文献

{"title":"Exploring Shared Genetic Features and Molecular Mechanisms between Non-Alcoholic Steatohepatitis and Hepatocellular Carcinoma through Bioinformatics.","authors":"ChengLong Tian, Zheng Li, QinLong Liu","doi":"10.2174/0113862073323011240912072514","DOIUrl":"https://doi.org/10.2174/0113862073323011240912072514","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular Carcinoma (HCC) is one of the most common malignant tumors in the world, characterized by high incidence, high malignancy, and low survival rate. Currently, 1/4 of adults in the world suffer from Non-Alcoholic Fatty Liver Disease (NAFLD), with an incidence rate of 27% in Asia.</p><p><strong>Methods: </strong>We used TCGA and GEO public database data sets to conduct weighted gene coexpression network analysis to identify relevant gene modules, defined the intersection of tumorigenesis-related modules and NASH development-related modules as shared genes, and then used single-factor Cox, LASSO, and multivariate Cox regression analysis screened out core shared genes and verified their prognostic value. We further investigated the relationship between core shared genes and immune infiltration, tumor mutational load, and drug sensitivity. Finally, RT-qPCR was used to verify its mRNA expression in different cell lines.</p><p><strong>Results: </strong>We identified Karyopherin α 2 (KPNA2) as the core shared gene between NASH and HCC. Patients were divided into low-risk groups and high-risk groups based on the expression of KPNA2. The prognosis of the low-risk group was significantly better than that of the highrisk group. Furthermore, we found significant differences in tumor immune cell infiltration, somatic mutations, microsatellite instability, and drug sensitivity between different expression groups.</p><p><strong>Conclusion: </strong>There are very few studies on the molecular mechanism of the relationship between NAFLD and HCC. Our study demonstrates that KPNA2 is a potential therapeutic target and immune-related biomarker for patients with NAFLD and HCC.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142361242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dihuangzicao Granules Regulate the AGE/RAGE/NF-κB Signaling Pathway to Inhibit Inflammation in Psoriatic Mice via Network Pharmacology and Experimental Validation.","authors":"Chong Lyu, Xianhua Qiao, Zhe Shi, Juanjuan Gao, Xiao Li, Shibin Jiang, Chengcheng Wang","doi":"10.2174/0113862073313333240912080819","DOIUrl":"10.2174/0113862073313333240912080819","url":null,"abstract":"<p><strong>Aim: </strong>Psoriasis is an immune-mediated skin disease that occurs worldwide and is characterized by high prevalence and chronicity. Psoriasis has a complex pathogenesis and is difficult to cure. Therefore, continuous exploration of the pathogenesis of psoriasis and the search for new drug treatment methods are crucial for improving treatment efficiency and reducing psychological damage to psoriasis patients. The active ingredients in Dihuang Zicao granules (DHZCG) can effectively treat psoriasis. Therefore, this study aimed to analyze the active ingredients of DHZCG and their potential mechanisms for treating psoriasis.</p><p><strong>Methods: </strong>The effective components of DHZCG were screened via the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Genetic information for psoriasis was retrieved from the GeneCards, OMIM and DisGENET databases. Protein-Protein Interaction (PPI) analysis was performed, and component‒target‒disease networks were constructed. Important molecular biological processes and signaling pathways were screened via GO and KEGG analyses. Molecular docking of the active ingredients and key targets was performed via AutoDock Vina (1.1.2). A mouse model of psoriasis was established and divided into a control group, model group, low-dose DHZCG group (L-DHZCG), medium-dose DHZCG group (M-DHZCG), and high-dose DHZCG group (H-DHZCG). Hematoxylin and Eosin (HE) staining was performed to determine the pathological changes in the skin of each group of mice, and the Psoriasis Area Severity Index (PASI) score was used to assess skin damage. ELISA and RT‒ PCR were used to measure the levels of the inflammatory factors TNF-a, IL-17A, and IL-23 in the serum and skin tissue of the mice, respectively. Western blotting was used to analyze the expression of proteins related to the AGE/RAGE signaling pathway. Immunofluorescence was used to examine the expression of the inflammatory factor NF-kB. Immunohistochemistry was used to measure IL-1β and TNF-a expression in skin tissues.</p><p><strong>Results: </strong>Sixty genes associated with psoriasis treatment by DHZCG, including core genes encoding IL-6, TNF-a, AKT1, IL-1β, TP53, NFKB1, BCL2, and MAPK3, were identified. Through the construction of a psoriasis mouse model, DHZCG treatment effectively reduced skin damage and significantly decreased the levels of the validated factors TNF-a, IL-17A, IL- 23, IL-1b, and NF-kB in the serum and damaged skin. Furthermore, the reduction in the levels of these inflammatory factors by DHZCG is associated with the downregulation of the AGE/RAGE signaling pathway.</p><p><strong>Conclusion: </strong>DHZCG reduces inflammation and alleviates psoriasis by downregulating the AGE/RAGE/NF-kB signaling pathway. This study is beneficial for providing a theoretical basis for the development of drugs for psoriasis and for offering personalized treatment strategies for the clinical management of psoriasis.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142361241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structural Insights and Biological Activities of Furan-Based Drugs in the Treatment of Human Diseases.","authors":"Avinash Kumar Mishra, Kuldeep Singh, Sunam Saha, Harsh Bhardwaj, Jeetendra Kumar Gupta, Kamal Shah, Shivendra Kumar, Divya Jain, Hritik Verma","doi":"10.2174/0113862073319757240912055303","DOIUrl":"https://doi.org/10.2174/0113862073319757240912055303","url":null,"abstract":"<p><p>Neurodegenerative diseases present significant public health challenges, driving the search for innovative therapeutic strategies. This review explores the neuroprotective potential of furan-containing compounds, which are derived from various natural and synthetic sources. These compounds are observed for their diverse pharmacological activities, including antioxidant and anti-inflammatory properties. By scavenging free radicals and mitigating oxidative stress, they address a key aspect of neurodegeneration. Additionally, furan derivatives modulate inflammatory pathways, potentially reducing neuroinflammation, a critical factor in the progression of these disorders. The review also highlights the impact of these compounds on neuronal survival and regeneration, suggesting their role in promoting neurogenesis and enhancing neuronal plasticity. Their interactions with neurotransmitter systems further support their neuroprotective effects, particularly in maintaining synaptic function and neurotransmission. The potential applications of furan-containing compounds are discussed concerning specific neurodegenerative diseases, such as Alzheimer's and Parkinson's. Insights from preclinical studies and in vitro experiments underscore their therapeutic promise across various experimental models. While still in the early stages of research, the evidence suggests that furan-containing compounds could be valuable in developing effective interventions for neurodegenerative diseases. This review emphasizes the need for further investigation into these compounds to realize their potential as neuroprotective agents fully.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the Therapeutic Potential of Rutin in Psoriasis: Network Pharmacology and Experimental Validation.","authors":"Xinyue Li, Yingying Han, Xinghua Liang, Yuan Hu, Guangping Lang","doi":"10.2174/0113862073336573240909113013","DOIUrl":"https://doi.org/10.2174/0113862073336573240909113013","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to investigate the potential therapeutic efficacy of rutin in the management of psoriasis and elucidate its underlying molecular mechanisms.</p><p><strong>Methods: </strong>A systems biology approach, utilizing network pharmacology, was employed to identify and analyze putative targets of rutin relevant to psoriasis. The impact of rutin on the Psoriasis Area and Severity Index (PASI) scores was assessed in an imiquimod (IMQ)-induced murine psoriasis model. Histopathological alterations in the skin lesions were examined using hematoxylin and eosin (H&E) staining. Expression levels of key inflammatory mediators, including Tnf, Hif1a, Ptgs2, Tlr4, Nfkb1, Mtor, and Il2, were quantified using quantitative real-time polymerase chain reaction (qRT-PCR).</p><p><strong>Results: </strong>A comprehensive analysis revealed 62 potential targets of rutin in the context of psoriasis, with these targets being part of 72 interconnected signaling pathways. In vivo studies demonstrated a significant reduction in PASI scores in rutin-treated mice compared to those in the control group. Additionally, rutin treatment was associated with marked improvements in skin lesions, characterized by reduced crust formation and epidermal thickness. qRT-PCR analysis indicated that rutin administration downregulated the mRNA expression of Tnf, Hif1a, Ptgs2, Tlr4, Nfkb1, Mtor, and Il2 in the lesional skin.</p><p><strong>Conclusion: </strong>These findings suggest that rutin holds promise as a therapeutic agent for psoriasis, as it effectively ameliorates IMQ-induced psoriasis-like skin inflammation in mice through modulation of multiple signaling pathways and inflammatory mediators.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the Potential Effects and Mechanism of Astragalus Membranaceus in Treating Ischemic Heart Failure Based on Network Pharmacology and Experimental Verification.","authors":"Chaoqun Xing, Xiao-Liang Xing, Hai Luo, Minjiang Huang, Xuemei Zhang, Zhiyong Yao","doi":"10.2174/0113862073322602240909113946","DOIUrl":"https://doi.org/10.2174/0113862073322602240909113946","url":null,"abstract":"<p><strong>Background: </strong>Astragalus membranaceus (AM) is a traditional Chinese medicine that has been clinically utilized as an adjunctive therapy for the treatment of myocardial ischemia and heart failure; however, its precise molecular mechanism of action remains unknown.</p><p><strong>Objective: </strong>This study aims to investigate the potential pharmacological effects and molecular mechanism of AM in the treatment of ischemic heart failure (IHF) using network pharmacology methods, molecular docking technology, and in vitro experiments.</p><p><strong>Methods: </strong>The active components and targets of AM were obtained from the TCMSP databases, while the disease targets of IHF were retrieved from GeneCards and OMIM databases. The analysis of overlapping targets between AM and IHF mainly included active compounds-targets network, PPI network, and GO and KEGG enrichment analysis. The association between active compounds and target proteins was verified through molecular docking. Additionally, an in vitro experimental model was used to evaluate the accuracy of the forecast results.</p><p><strong>Results: </strong>The network pharmacological analysis revealed that quercetin, kaempferol, 7-Omethylisomucronulatol, formononetin, and isorhamnetin were the core active components of AM in treating IHF. The core targets included AKT1, IL6, IL1B, PTGS2, CASP3, MMP9, and HIF1A. The molecular docking results demonstrated a strong binding affinity between these active components and targets. The KEGG pathway analysis suggested that the PI3K-AKT signaling pathway might play a central role in mediating AM's therapeutic effects on IHF. In vitro experiments demonstrated that AM treatment enhanced cell viability, reduced heart failure biomarkers, and suppressed cell apoptosis. Furthermore, the western blot analyses indicated that AM treatment effectively regulated AKT1 phosphorylation in an experimental model of IHF.</p><p><strong>Conclusion: </strong>Through integrated network pharmacological analysis, molecular docking technology, and in vitro experimental validation, it was demonstrated that AM can effectively mitigate IHF through activating PI3K-AKT signaling pathway. These findings significantly advance our understanding of the molecular mechanisms in IHF treatment and contribute further to promoting the clinical application of AM.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antioxidant Properties of Teucrium polium Extract Contribute to Neurochemical and Brain Structural Modulations in Nicotine-Induced Mice.","authors":"Afaf A Alatawi, Jamaan S Ajarem, Saud A Alarifi, Saleh A Al-Quraishy, Esam M Al-Shaebi, Sarah A Alawwad, Rashed N Herqash, Sally M Khadrawy, Noha A Ahmed, Chuanyi Wang, Saleh N Maodaa","doi":"10.2174/0113862073312840240910102115","DOIUrl":"https://doi.org/10.2174/0113862073312840240910102115","url":null,"abstract":"<p><strong>Introduction: </strong>Tobacco use is a major global health issue linked to psychiatric illnesses and high mortality rates. Nicotine, the primary compound absorbed during smoking, causes harm to various organs, particularly the brain. The current study examined the modulatory effect of Teucrium polium extract (TPE) on nicotine-induced biochemical and histological changes in the brains of mice.</p><p><strong>Methods: </strong>Twenty-four mice were divided into four groups and were treated for three weeks. Group one was the control; Group two received 100 mg/kg TPE orally; Group three was subcutaneously injected with 2.5 mg/kg nicotine, and Group four received both nicotine and TPE.</p><p><strong>Results: </strong>The brain tissue of the nicotine-induced group showed histopathological alterations and oxidative stress as indicated by increased lipid peroxidation and nitric oxide levels concomitant with decreased glutathione content and superoxide dismutase activity. DNA fragmentation was also detected by comet assay. Treatment with TPE significantly decreased oxidative stress and DNA fragmentation while increasing antioxidant biomarkers. Histopathological changes were also diminished.</p><p><strong>Conclusion: </strong>Through the antioxidant activity of TPE, it protected against nicotine-induced neurotoxicity in mice by impacting oxidative stress, DNA fragmentation, and brain histopathological changes.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Network Pharmacology and Validation of the Combinative Therapy of Ligusticum striatum DC. and Borneolum against Cerebral Ischemia.","authors":"Ming Ruan, Gaohong Lv, Xueqing Wang, Fengjiao Deng, Tianya Xia, Bin Yu, Shengjin Liu","doi":"10.2174/0113862073317255240902075511","DOIUrl":"https://doi.org/10.2174/0113862073317255240902075511","url":null,"abstract":"<p><strong>Background: </strong>Ligusticum striatum DC. (LDC) is often prescribed for Cerebral Ischemia (CI) and is commonly combined with Borneolum (BO) to enhance therapeutic outcomes. However, its specific active ingredients and underlying mechanisms remain unclear.</p><p><strong>Objective: </strong>This study aimed to identify the active ingredients and mechanisms of LDC and BO combination therapy against CI using network pharmacology, molecular docking, and in vivo experiments.</p><p><strong>Methods: </strong>Potential active ingredients and targets were sourced from relevant databases, and a drug-component-target-disease network was constructed to pinpoint key ingredients. Subsequently, a protein-protein interaction analysis was conducted to confirm the key targets. Following enrichment analyses of Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG), molecular docking was employed to evaluate binding energies. Finally, the therapeutic effects and mechanisms of the combination against CI were validated through in vivo experiments using male ICR mice.</p><p><strong>Results: </strong>Venn analysis identified a total of 41 components and 292 potential targets. The drugcomponent-target-disease network revealed that the key components in LDC were palmitic acid, tetramethylpyrazine, and (Z)-ligustilide, while those in BO were (+)-borneol, β-elemene, and (-)- borneol. The PPI analysis highlighted seven crucial targets. Docking results confirmed a stable affinity between these components and their targets. KEGG enrichment analysis indicated that the mechanism involved the PI3K/AKT signaling pathway. Subsequently, in vivo experiments confirmed that the combination ameliorated abnormal hippocampus morphology and reduced the release of inflammatory factors through the activation of the PI3K/AKT signaling pathway.</p><p><strong>Conclusion: </strong>The combination of LDC and BO markedly improved CI and inhibited inflammation response via activating the PI3K/AKT pathway.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142281496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Thorough Review on Ethnomedicinal Value of Bioactive Compounds of Pteridophytes against Cancer: Clinical Applications and Future Prospects.","authors":"Priya Bansal, Neeraj Kumar, Sharda Sambhakar, Abhishek Kumar, Deepti Katiyar","doi":"10.2174/0113862073318080240902080232","DOIUrl":"https://doi.org/10.2174/0113862073318080240902080232","url":null,"abstract":"<p><p>Most cancers have become immune to normal cancer therapy, like chemotherapy and radiation. Therefore, exploring more effective and economical treatment options is important. Plants and herbs contain substances called phytochemicals, which have biological effects. Many phytochemicals having antioxidant and anticancer properties have been studied previously. There is increasing evidence that phytochemicals' anti-carcinogenic benefits originate from their ability to inhibit oxidation, inflammation, cell proliferation, and angiogenesis. These phytochemicals inhibit the spread of cancer by controlling the cell cycle and other molecular processes, such as metastasis. Along with therapeutic potential, other advantages, like their abundance, greater tolerability, and economic use, increase their utility in cancer therapeutics. In recent years, a number of scientists have examined lycophytes and ferns for their potential medicinal and phytochemical properties. This analysis emphasizes the significance of chemicals obtained from ferns and their derivatives in therapeutics. The authors discuss the pteridophyte's anti-cancer properties and other medical uses in this article. This information may help researchers in further research related to the most promising anticancer phytochemicals and their possibility as alternative drugs against cancer.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142281494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Study on Shenbao Tablet in Treating Kidney-yang Deficiency Syndromebased on Metabolomics","authors":"Qing-gang Zhou, Bao-xia Han, Huan Yi, Zhao Geng, Xiao-jun Gou","doi":"10.2174/0113862073316238240827110846","DOIUrl":"https://doi.org/10.2174/0113862073316238240827110846","url":null,"abstract":"Aim: The aim of this study was to elucidate the mechanism of action of Shenbao tablets using metabolomics approach. Background: Kidney-Yang deficiency is a common syndrome type in traditional Chinese Medicine (TCM) syndrome typology, closely related to disorders of multiple metabolic pathways and is the root cause and underlying syndrome type of many diseases. Shenbao tablets can significantly improve the main symptoms of kidney yang deficiency syndrome, but the mechanism of action of Shenbao tablets on kidney yang deficiency syndrome is still unknown. Methods: The rats were intraperitoneally injected with hydrocortisone once a day for 40 days to simulate the syndrome. Traditional pharmacodynamic indicators (body mass, biochemical indicators and pathology) were used to evaluate the efficacy of the medicine. Serum, urine and feces were collected from rats. UPLC/MS metabolomics method was used to study the overall metabolic profile of serum, while GC/MS metabolomics method was used to study the metabolic spectrum of urine and feces. Results: Results showed that the syndrome was significantly improved in the treatment group, and obvious metabolic disorders were observed in rats with the syndrome, with 47 potential biomarkers identified. Pathway analysis showed that nicotinate and nicotinamide metabolism, glycine, serine and trione metabolism, aminoacyl tRNA biosynthesis, glycoxylate and dicarboxylate metabolism were the major ways for Shenbao tablet to improve kidney-yang deficiency syndrome. Conclusion: The mechanism of action of Shenbao tablet in improving the syndrome involves the regulation of energy metabolism, amino acid metabolism, bile acid metabolism, fatty acid metabolism and intestinal microorganisms. This work shows that metabolomics is a promising tool for studying the essence of syndrome theory in TCM and the mechanisms of TCM.","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":"79 1","pages":""},"PeriodicalIF":1.8,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142258712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigation of the Mechanism of Siweixizangmaoru Decoction in Improving CIA-Induced Arthritis in Rats Based on Network Pharmacology and Experimental Verification","authors":"Yanfei Niu, Yanxiang Yuan, Tong Wang, Ruiying Yuan, Min Zhang, Sicen Wang, Dikye Tsering, Shan Huang, Bin Li","doi":"10.2174/0113862073326896240901110932","DOIUrl":"https://doi.org/10.2174/0113862073326896240901110932","url":null,"abstract":"Background: Rheumatoid Arthritis (RA) is a chronic autoimmune disease with a complex etiology. Siweixizangmaoru Decoction (SXD) has been used to treat RA in Tibet for a long history as a classic Tibetan medicine formula. However, the potential pharmacological mechanism has not been elucidated yet. Aims: The aim of this study was to evaluate the efficacy and mechanism of action of SXD in the treatment of RA using network pharmacology and molecular docking analysis. Method: Network pharmacology was employed to identify the potential bioactive components and key targets of SXD for the treatment of RA. Molecular docking of key targets and potential compounds was conducted. High-performance liquid chromatography was performed to validate the predicted active components of SXD. We established a rat model of RA and evaluated the histopathology of each group of rats. In addition, the levels of inflammatory factors in serum and the expression levels of PI3K/AKT and MAPK pathway-related proteins in synovial tissue were detected. Results: The results of network pharmacological analyses indicated that apigenin, rhamnolipids, kaempferol, quercetin, and naringenin are potential bioactive components of SXD for the treatment of rheumatoid arthritis and that their therapeutic effects may be related to the PI3K-Akt and MAPK pathways. The results of in vivo experiments show that SXD improved the arthritis index, significantly reduced joint swelling, and improved synovial inflammation and cartilage destruction. Conclusion: Network pharmacology, along with experimental validation, provided a useful approach for understanding the pharmacological mechanism of Siweixizangmaoru decoction in RA.","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":"10 1","pages":""},"PeriodicalIF":1.8,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142258709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}