Protective effects and mechanisms of Lizhong decoction against non-alcoholic fatty liver disease in a rat model.
Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan
OBJECTIVE:To investigate the protective effects and molecular mechanisms of Lizhong decoction (, LZD) against non-alcoholic fatty liver disease (NAFLD). METHODS:Male Wistar rats were fed a high-fat diet for four weeks to induce NAFLD, and were administered LZD by gavage for four weeks. Potential therapeutic targets for NAFLD were analyzed using network pharmacology. Liver pathology was evaluated using Oil Red O and hematoxylin-eosin staining. Furthermore, mitochondrial function, lipid metabolism, oxidative stress, and inflammatory response were examined. RESULTS:Rats with NAFLD exhibited high levels of hepatic damage and cholesterol deposition. Moreover, apoptosis was increased, superoxide dismutase and glutathione content were reduced, malondialdehyde content was increased, and the protein expression of inflammatory cytokines and p-c-Jun N-terminal kinase was increased. The LZD treatment ameliorated mitochondrial dysfunction, reduced liver damage, inhibited oxidative stress and inflammatory response, upregulated peroxisome proliferator-activated receptor (PPAR)-γ expression, and suppressed dipeptidyl peptidase 4 (DPP4) expression in the liver. CONCLUSION:It was found that LZD alleviates NAFLD by activating PPAR-γ and inhibiting DPP4.
10.19852/j.cnki.jtcm.2022.05.009
A UPLC-Q-TOF/MS and network pharmacology method to explore the mechanism of Anhua fuzhuan tea intervention in nonalcoholic fatty liver disease.
Food & function
The possible mechanism by which the active components of Anhua fuzhuan tea act on FAM in NAFLD lesions was investigated. 83 components of Anhua fuzhuan tea were analysed by UPLC-Q-TOF/MS. Luteolin-7-rutinoside and other compounds were first discovered in fuzhuan tea. According to the TCMSP database and the Molinspiration website tool to predict and review the literature reports, 78 compounds were identified in fuzhuan tea with possible biological activities. The PharmMapper, Swiss target prediction, and SuperPred databases were used to predict the action targets of biologically active compounds. The GeneCards, CTD, and OMIM databases were mined for NAFLD and FAM genes. Then, a fuzhuan Tea-NAFLD-FAM Venn diagram was constructed. Using the STRING database and CytoHubba program of Cytoscape software, protein interaction analysis was performed, and 16 key genes, including PPARG, were screened. GO function and KEGG enrichment analyses of the screened key genes showed that Anhua fuzhuan tea may regulate FAM in the process of NAFLD through the AMPK signalling pathway, nonalcoholic fatty liver disease pathway, . After constructing an active ingredient-key target-pathway map with Cytoscape software, combined with literature reports and BioGPS database analysis, we believe that among the 16 key genes, SREBF1, FASN, ACADM, HMGCR, and FABP1 have potential in the treatment of NAFLD. Animal experiments confirmed the effect of Anhua fuzhuan tea in improving NAFLD and confirmed that this tea can interfere with the gene expression of the above five targets by the AMPK/PPAR pathway, providing support for Anhua fuzhuan tea interfering with FAM in NAFLD lesions.
10.1039/d2fo02774g
Prediction of the mechanisms of action of Qutan Huoxue decoction in non-alcoholic steatohepatitis (NASH): a network pharmacology study and experimental validation.
Pharmaceutical biology
CONTEXT:Qutan Huoxue decoction (QTHX) is used to treat non-alcoholic steatohepatitis (NASH) with good efficacy in the clinic. However, the mechanism is not clear yet. OBJECTIVE:This study investigates the mechanism of QTHX in the treatment of NASH. MATERIALS AND METHODS:Potential pathways of QTHX were predicted by network pharmacology. Fourty Sprague Dawley (SD) rats (half normal diet, half high-fat diet) were fed six to eight weeks, primary hepatocytes and Kupffer cells were extracted and co-cultured by the 0.4-micron trans well culture system. Then, the normal co-cultured cells were treated by normal serum, the NASH co-cultured cells were treated with various concentrations of QTHX-containing serum (0, 5, 7.5 or 10 μg/mL) for 24 h. The expression of targets were measured with Activity Fluorometric Assay, Western blot and PCR assay. RESULTS:Network pharmacology indicated that liver-protective effect of QTHX was associated with its anti-inflammation response, oxidative stress, and lipid receptor signalling. 10 μg/mL QTHX significantly reduced the inflammation response and lipid levels in primary hepatocytes (ALT: 46.43 ± 2.76 U/L, AST: 13.96 ± 1.08 U/L, TG: 0.25 ± 0.01 mmol/L, TC: 0.14 ± 0.05 mmol/L), comparing with 0 μg/mL NASH group (ALT: 148 ± 9.22 U/L, AST: 53.02 ± 2.30 U/L, TG: 0.74 ± 0.07 mmol/L, TC: 0.91 ± 0.07 mmol/L) ( < 0.01). Meanwhile, QTHX increased expression of SOCS1 and decreased expression of TLR4, Myd88, NF-κB. CONCLUSIONS:The study suggested that QTHX treats NASH in rats by activating the SCOS1/NF-κB/TLR4 pathway, suggesting QTHX could be further developed as a potential liver-protecting agent.
10.1080/13880209.2023.2182892
Qinlian hongqu decoction ameliorates hyperlipidemia via the IRE1-α/IKKB-β/NF-κb signaling pathway: Network pharmacology and experimental validation.
Journal of ethnopharmacology
ETHNOPHARMACOLOGICAL RELEVANCE:Qinlian Hongqu decoction (QLHQD) is a traditional Chinese medicine (TCM) formula. It has previously been found to mitigate hyperlipidemia, although its mechanism requires further clarification. AIM OF THE STUDY:This study explored QLHQD's mechanism in treating hyperlipidemia based on network pharmacology and experimental validation. MATERIALS AND METHODS:The components of QLHQD were analyzed by means of ultrahigh performanceliquid chromatography-quadrupole/orbitrapmass spectrometry (UHPLC-Q-Orbitrap-HRMS) and the targets of hyperlipidemia were predicted using the Swiss ADME, GeneCards, OMIM, DrugBank, TTD, and PharmGKB databases. A drug-component-target-disease network was constructed using Cytoscape v3.7.1. Moreover, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses were performed using the Bioinformatics platform. Based on the KEGG results, the non-alcoholic fatty liver disease signaling pathways were selected for experimental validation in an animal model. RESULTS:We identified 34 components of QLHQD, 94 targets of hyperlipidemia, and 18 lipid metabolism-related pathways from the KEGG analysis. The results of the animal experiment revealed that QLHQD alleviated lipid metabolism disorders, obesity, insulin resistance, and inflammation in rats with hyperlipidemia induced by high-fat diets. Additionally, it reduced the expression of IRE1-α, TRAF2, IKKB-β, and NF-κB proteins in the liver of hyperlipidemic rats. CONCLUSION:QLHQD is able to significantly mitigate hyperlipidemia induced via high-fat diets in rats. The mechanism of action in this regard might involve regulating the IRE1-α/IKKB-β/NF-κB signaling pathway in the liver, thereby attenuating inflammatory responses and insulin resistance.
10.1016/j.jep.2023.116856
Study on the action mechanism of the Polygonum perfoliatum L. on non-alcoholic fatty liver disease, based on network pharmacology and experimental validation.
Journal of ethnopharmacology
ETHNOPHARMACOLOGICAL RELEVANCE:Traditional Chinese medicine (TCM) holds that non-alcoholic fatty liver disease (NAFLD) belong to the category of "thoracic fullness". Polygonum perfoliatum L. (PPL), a Chinese medicinal herb with the effect of treating thoracic fullness, was recorded in the ancient Chinese medicine book "Supplements to Compendium of Materia Medica". It has been used since ancient times to treat NAFLD. However, the underlying mechanism and active components of PPL against NAFLD remains unclear. AIM OF STUDY:To identify the main active components and the anti-NAFLD mechanism of PPL. MATERIALS AND METHODS:Network pharmacology, UPLC/QE-HFX analysis, and molecular docking were employed to determine the main bioactive compounds and key targets of PPL for the NAFLD treatment. This effect was further validated with administration of PPL (200 mg/kg and 400 mg/kg) to NAFLD model mice for 5 weeks. Systemic signs of obesity, biochemical parameters, and histological changes were characterized. Immunohistochemistry, western blot, and PCR analysis were conducted to elucidate the mechanistic pathways through which PPL exerts its effects. RESULTS:Network pharmacology revealed 77 crossover genes between the PPL and NAFLD. The kyoto encyclopedia of genes and genomes (KEGG) analysis show that PPL treat NAFLD mainly regulating glucose-lipid metabolism mediated by PI3K/AKT signal pathway. The Gene Ontology (GO) enrichment analysis show that PPL treat NAFLD mainly regulating inflammation mediated by cytokine-mediated signaling pathway. In accordance with the anticipated outcomes, administration of PPL in a dose-dependent manner effectively mitigated insulin resistance induced by a high-fat diet (HFD) by activating the PI3K/AKT signaling pathway. Histopathological evaluation corroborated the hepatoprotective effects of PPL against HFD-induced hepatic steatosis, as evidenced by the inhibition of de novo fatty acid synthesis and promotion of fatty acid β-oxidation (FAO). Further research showed that PPL blocked cytokine production by inhibiting the NF-κB pathway, thereby reducing immune cell infiltration. Furthermore, five flavonoids from PPL, including quercetin, baicalein, galangin, apigenin, and genistein were identified as key compounds based on ingredient-target-pathway network analysis. Molecular docking show that these active compounds have favorable binding interactions with AKT1, PIK3R1, and MAPK1, further confirming the impact of PPL on the PI3K/AKT pathway. CONCLUSIONS:Through the combination of network pharmacology prediction and experimental validation, this work determined that therapeutic effect of PPL on NAFLD, and such protective effect is mediated by activating PI3K/AKT-mediated glucolipid metabolism pathway and hepatic NF-κB-mediated cytokine signaling pathway.
10.1016/j.jep.2023.117330
Integrating transcriptomics and network pharmacology to reveal the mechanisms of total Rhizoma Coptidis alkaloids against nonalcoholic steatohepatitis.
Journal of ethnopharmacology
ETHNOPHARMACOLOGICAL RELEVANCE:Non-alcoholic steatohepatitis (NASH) has emerged as a major cause of cirrhosis and hepatocellular carcinoma, posing a significant threat to public health. Rhizoma Coptidis, a traditional Chinese medicinal herb has been shown to have significant curative effects on liver diseases. Total Rhizoma Coptidis Alkaloids (TRCA) is a primarily alkaloid mixture extracted from Rhizoma Coptidis, and its constituents are widely accepted to have hepatoprotective effects. AIM OF THE STUDY:This work aimed to investigate the efficacy and potential mechanisms of TRCA in ameliorating NASH through both in vitro experiments and in vivo mouse models. MATERIALS AND METHODS:The study employed a mice model induced by a high-fat diet (HFD) to evaluate the effectiveness and pharmacological mechanisms of TRCA in alleviating NASH. Transcriptomic sequencing and network pharmacology were used to explore the possible targets and mechanisms of TRCA to ameliorate NASH. Further validation was performed in free fatty acid (FFA)-induced human hepatocytes (LO2) and human hepatocellular carcinoma cells (HepG2). RESULTS:TRCA effectively ameliorated the main features of NASH such as lipid accumulation, hepatitis and hepatic fibrosis in the liver tissue of mice induced by HFD, as well as improved glucose tolerance and insulin resistance in mice. Combined with transcriptomic and network pharmacological analyses, 68 core targets associated with the improvement of NASH by TRCA were obtained. According to the KEGG results, the core targets were significantly enriched in the PI3K-AKT signaling pathway whereas TRCA ameliorated the aberrant down-regulation of the PI3K-AKT signaling pathway induced by HFD. Furthermore, the five highest-ranked genes were obtained by PPI network analysis. Moreover, our findings suggest that TRCA may impede the progression of HFD-induced NASH by regulating the expression of PPARG, MMP9, ALB, CCL2, and EGFR. CONCLUSIONS:TRCA can ameliorate HFD-induced liver injury by modulating aberrant downregulation of the PI3K-AKT signaling pathway. Key proteins such as PPARG, MMP9, ALB, CCL2, and EGFR may be critical targets for TRCA to ameliorate NASH. This finding supports using Rhizoma Coptidis, a well-known herbal medicine, as a potential therapeutic agent for NASH.
10.1016/j.jep.2023.117600
Integrating metabolomics and network pharmacology to reveal the mechanisms of Delphinium brunonianum extract against nonalcoholic steatohepatitis.
Journal of ethnopharmacology
ETHNOPHARMACOLOGICAL RELEVANCE:Herba Delphinii Brunoniani, a Tibetan Material Medica, derived from the aerial parts of Delphinium brunonianum Royle, possesses efficacy of cooling blood to remove apthogentic heat, and dispelling wind to arrest itching, and has been used for the treatment for liver disease according to Tibetan Medicine Theories in Shel Gong Shel Phreng. However, the mechanisms of action remain unclear. AIM OF THE STUDY:This work aimed to investigate the efficacy mechanism of Delphinium brunonianum extract (DBE) on nonalcoholic steatohepatitis (NASH), a kind of liver disease by integrating serum metabolomics and network pharmacology analysis. MATERIALS AND METHODS:In this study, NASH model mice were established by a high-fat diet. The indexes of lipid accumulation, insulin resistance, and inflammatory reaction were used to evaluate the efficacy of DBE. A combination of UHPLC-QTOF-MS based metabolomics and network pharmacology was established to illustrate the serum biomarkers of NASH mice and to demonstrate the anti-NASH mechanisms of DBE. Serum metabolomics demonstrated potential metabolites and the corresponding metabolic pathways in the efficacy of DBE. Network pharmacology screened the targets of DBE against NASH. Finally, the mechanisms of DBE against NASH were verified by in-vivo pharmacology. RESULTS:Metabolomics revealed that DBE significantly regulated the abnormal levels of twenty-two metabolites, which involved the biosynthesis of unsaturated fatty acids and steroid hormone, linoleic acid metabolism, arachidonic acid metabolism, and alpha-Linolenic acid metabolism pathways. Network pharmacology showed that DBE exhibited anti-NASH effects through regulating the targets of PTGS2, PLA2, ALOX5, ALOX15, FASN, and CYP450. Finally, united pharmacological verification result, we found that the mechanisms of DBE against NASH may be related to the regulation of the unsaturated fatty acids biosynthesis and the arachidonic acid metabolism pathway. CONCLUSIONS:Integrating serum metabolomic and network analysis, we found that DBE might inhibit the pathological process of NASH by regulating the relative targets and the metabolic pathways, which may be a potential mechanism for the anti-NASH efficacy of DBE. This integrated strategy also provided a rational way for revealing the pharmacodynamic mechanisms of multi-components, multi-targets, and multi-pathways in Traditional Chinese Medicine (TCM).
10.1016/j.jep.2022.115268
Network Pharmacology to Reveal the Molecular Mechanisms of Rutaceous Plant-derived Limonin Ameliorating Non-alcoholic Steatohepatitis.
Critical reviews in immunology
BACKGROUND:Limonin shows promise in alleviating non-alcoholic fatty liver disease. We investigated the mechanisms of limonin against non-alcoholic steatohepatitis (NASH) using network pharmacology and molecular docking. METHODS:Public databases provided NASH- and limonin-associated targets. VennDiagram identified potential limonin targets for NASH. Enrichment analysis explored the limonin-NASH relationship. PPI network analysis, CytoHubba models, and bioinformatics identified hub genes for NASH treatment. Molecular docking assessed limonin's binding ability to hub targets. RESULTS:We found 37 potential limonin targets in NASH, involved in oxidative stress, inflammation, and signaling pathways. PPI network analysis revealed seven hub genes (STAT3, NFKBIA, MTOR, TLR4, CASP8, PTGS2, NFKB1) as NASH treatment targets. Molecular docking confirmed limonin's binding to STAT3, CASP8, and PTGS2. Animal experiments on high-fat diet mice showed limonin reduced hepatic steatosis, lipid accumulation, and expression of p-STAT3/STAT3, CASP8, and PTGS2. CONCLUSION:Limonin's therapeutic effects in NASH may stem from its antioxidant and anti-inflammatory properties. STAT3, CASP8, and PTGS2 are potential key targets for NASH treatment, warranting further investigation.
10.1615/CritRevImmunol.2023050080
and demonstration of the regulatory mechanism of Qi-Ge decoction in treating NAFLD.
Annals of medicine
BACKGROUND:Nonalcoholic fatty liver disease (NAFLD), a chronic and progressive liver disease, often causes steatosis and steatohepatitis. Qi-Ge decoction (QGD) shows a good effect against NAFLD in the clinic. But the molecular mechanism for QGD in improving NAFLD is unknown. PURPOSE:This study explored the molecular mechanism of QGD in NAFLD model rats using comprehensive network pharmacology, molecular docking and verification strategies. METHODS:Active components and targets of QGD were obtained from public database. The overlapped genes between QGD and NAFLD targets were analyzed by enrichment analysis. Active components and targets were used to predict molecular docking analysis. Finally, seven key targets were screened out and the gene expression were verified in the NAFLD rat's liver tissues after QGD treatment. RESULTS:Fifty-eight common QGD therapeutic targets were associated with NAFLD. Molecular docking demonstrated that seven targets had strong binding ability for the corresponding active ingredients. GO analysis identified 18 biological process entries, which were mainly related to regulation of lipid storage, lipid localization and peptide transport. KEGG analysis identified multiple signaling pathways, which were mainly associated with tumor necrosis factor signaling and NAFLD. data confirmed that the effect of QGD in the treatment of NAFLD was mainly exerted through improving liver steatosis and inflammatory cell infiltration. Additionally, QGD upregulated the expression of MAPK8 and ESR1 and downregulated the transcriptional expression of IL6, VEGFA, CASP3, EGFR and MYC. These targets may affect lipid metabolism by regulating lipid storage and inflammation. CONCLUSION:The integration of results obtained and indicated that QGD regulates multiple targets, biological processes and signaling pathways in NAFLD, which may represent a complex molecular mechanism by which QGD improves NAFLD.Key messagesQGD intervention is related to multiple biological processes such as inflammation, oxidation and cell apoptosis in NAFLD.Lipid and atherosclerosis, TNF signaling pathway, IL-17 signaling pathway, non-alcoholic fatty liver disease and AGE-RAGE signaling pathway in diabetic complications are the main pathways for QGD intervention NAFLD.The active components of QGD can form good binding with relevant target proteins through intermolecular forces, exhibiting excellent docking activity.
10.1080/07853890.2023.2200258
Kangtaizhi Granule Alleviated Nonalcoholic Fatty Liver Disease in High-Fat Diet-Fed Rats and HepG2 Cells via AMPK/mTOR Signaling Pathway.
Zhang Jiaxin,Du Haixia,Shen Menglan,Zhao Zhengqi,Ye Xinmiao
Journal of immunology research
Kangtaizhi granule (KTZG) is a Chinese medicine compound prescription and has been proven to be effective in nonalcoholic fatty liver disease (NAFLD) treatment clinically. However, the underlying mechanisms under this efficacy are rather elusive. In the present study, network pharmacology and HPLC analysis were performed to identify the chemicals of KTZG and related target pathways for NAFLD treatment. Network pharmacology screened 42 compounds and 79 related targets related to NAFLD; HPLC analysis also confirmed six compounds in KTZG. Further experiments were also performed. In an study, SD rats were randomly divided into five groups: control (rats fed with normal diet), NAFLD (rats fed with high-fat diet), and KTZG 0.75, 1.5, and 3 groups (NAFLD rats treated with KTZG 0.75, 1.5, and 3 g/kg, respectively). Serum lipids were biochemically determined; hepatic steatosis and lipid accumulation were evaluated with HE and oil red O staining. In an study, HepG2 cells were incubated with 1 mM FFA to induce lipid accumulation with or without KTZG treatment. MTT assay, intracellular TG level, oil red O staining, and glucose uptake in cells were detected. Western blotting and immunohistochemical and immunofluorescence staining were also performed to determine the expression of lipid-related genes PPAR-, SREBP-1, p-AKT, FAS, and SIRT1 and genes in the AMPK/mTOR signaling pathway. In high-fat diet-fed rats, KTZG treatment significantly improved liver organ index and serum lipid contents of TG, TC, LDL-C, HDL-C, ALT, and AST significantly; HE and oil red O staining also showed that KTZG alleviated hepatic steatosis and liver lipid accumulation. In FFA-treated HepG2 cells, KTZG treatment decreased the intracellular TG levels, lipid accumulation, and attenuated glucose uptake significantly. More importantly, lipid-related genes PPAR-, SREBP-1, p-AKT, FAS, and SIRT1 expressions were ameliorated with KTZG treatment in high-fat diet-fed rats and FFA-induced HepG2 cells. The p-AMPK and p-mTOR expressions in the AMPK/mTOR signaling pathway were also modified with KTZG treatment in high-fat diet-fed rats and HepG2 cells. These results indicated that KTZG effectively ameliorated lipid accumulation and hepatic steatosis to prevent NAFLD in high-fat diet-fed rats and FFA-induced HepG2 cells, and this effect was associated with the AMPK/mTOR signaling pathway. Our results suggested that KTZG might be a potential therapeutic agent for the prevention of NAFLD.
10.1155/2020/3413186
Network pharmacology and molecular docking-based investigation on traditional Chinese medicine Astragalus membranaceus in oral ulcer treatment.
Medicine
To analyze the mechanism of Astragalus membranaceus (AM) in molecular level in the oral ulcer (OU) treatment with reference to network pharmacology. Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform database was used in screening the AM active components and AM action targets; GeneCards database was used to screen OU targets; the common target were screened by Venny online tool; Cytoscape software was applied to construct the target gene regulation map of AM active components; STRING database was used to construct the protein-protein interaction network and the key targets were screened as per degree value; gene ontology enrichment and KEGG pathway enrichment of interactive genes were calculated through David database. There were 17 active ingredients and 429 target spots in Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform database. There are 606 target genes for OU in GeneCards database. There are 67 common targets, including 10 key targets: IL10, IL6, TNF, IL1B, CXCL8, CCL2, TLR4, IL4, ICAM1, and IFNG. It involves 30 gene ontology terms and 20 KEGG signal channels. The molecular docking results showed that quercetin and kaempferol had a good binding activity with IL6, IL1B, TNF, and CCL2. Network pharmacological analysis shows that AM can regulate multiple signal pathways through multiple targets to treat OU.
10.1097/MD.0000000000034744
Progress and Prospects of Research Ideas and Methods in the Network Pharmacology of Traditional Chinese Medicine.
Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques
In recent years, the emerging network pharmacology has been extensively applied to the field of traditional Chinese medicine and has made great contributions to the modernization of TCM. Therefore, this paper provides an overview of the progress of research ideas and methods in the network pharmacology in the last few years in the field of traditional Chinese medicine and presents insights into future research methods and ideas in the network pharmacology. Problems with the current network pharmacology are discussed and prospects of its future development are put forward.
10.18433/jpps32911
Network pharmacology-based strategy to investigate the bioactive ingredients and molecular mechanism of Evodia rutaecarpa in colorectal cancer.
BMC complementary medicine and therapies
BACKGROUND:Evodia rutaecarpa, a traditional herbal drug, is widely used as an analgesic and antiemetic. Many studies have confirmed that Evodia rutaecarpa has an anticancer effect. Here, our study explored the bioactive ingredients in Evodia rutaecarpa acting on colorectal cancer (CRC) by utilizing network pharmacology. METHODS:We clarified the effective ingredients and corresponding targets of Evodia rutaecarpa. CRC-related genes were obtained from several public databases to extract candidate targets. Candidate targets were used to construct a protein-protein interaction (PPI) network for screening out core targets with topological analysis, and then we selected the core targets and corresponding ingredients for molecular docking. Cell proliferation experiments and enzyme-linked immunosorbent assays (ELISAs) verified the anticancer effect of the bioactive ingredients and the results of molecular docking. RESULTS:Our study obtained a total of 24 bioactive ingredients and 100 candidate targets after intersecting ingredient-related targets and CRC-related genes, and finally, 10 genes-TNF, MAPK1, TP53, AKT1, RELA, RB1, ESR1, JUN, CCND1 and MYC-were screened out as core targets. In vitro experiments suggested that rutaecarpine excelled isorhamnetin, evodiamine and quercetin in the inhibition of CRC cells and the release of TNF-α was altered with the concentrations of rutaecarpine. Molecular docking showed that rutaecarpine could effectively bind with TNF-α. CONCLUSION:The pairs of ingredients-targets in Evodia rutaecarpa acted on CRC were excavated. Rutaecarpine as a bioactive ingredient of Evodia rutaecarpamight effectively inhibit the proliferation of CRC cells by suppressing TNF-α.
10.1186/s12906-023-04254-8
A network pharmacology and molecular docking approach to reveal the mechanism of Chaihu Anxin Capsule in depression.
Frontiers in endocrinology
Introduction:As one of the most frequently diagnosed mental disorders, depression is expected to become the most common disease worldwide by 2030. Previous studies have shown that Chaihu Anxin Capsule has powerful antidepressant effects. However, its mechanisms are not fully understood. The aim of our research is to reveal the mechanisms of Chaihu Anxin Capsule in treating depression. Methods:Information about the ingredients of the herb was gathered using the TCMSP. Genes associated with antidepressants were gathered from the GeneCards database. An "herbal-ingredient-target" network was constructed and analyzed using Cytoscape software. The PPI network of the antidepressant targets of Chaihu Anxin Capsule was constructed using the STRING database. KEGG pathway and GO enrichment were used to analyze the antidepressant targets. Molecular docking technology was used to confirm the capacity of the primary active ingredients of Chaihu Anxin Capsule to bind to central targets using AutoDock Vina and PyMOL software. Results:Network analysis showed that five targets might be therapeutic targets of Chaihu Anxin Capsule in depression, namely, JUN, IL6, AKT1, TP53, and STAT3. The gene enrichment analysis implied that Chaihu Anxin Capsule benefits patients with depression by modulating pathways related to lipids and atherosclerosis and the AGE-RAGE signaling pathway in diabetic complications. Molecular docking analyses revealed that JUN, IL6, AKT1, TP53, and STAT3 had good affinities for quercetin, beta-sitosterol and kaempferol. Conclusion:According to the bioinformatics data, the antidepressant effects of Chaihu Anxin Capsule may be primarily linked to cholesterol and atherosclerosis as well as the AGE-RAGE signaling pathway in diabetic complications. These results emphasize that the expected therapeutic targets may be possible indicators for antidepressant activity.
10.3389/fendo.2023.1256045
Network pharmacology and molecular docking approach to elucidate the mechanisms of Liuwei Dihuang pill in diabetic osteoporosis.
Journal of orthopaedic surgery and research
BACKGROUND:Diabetic osteoporosis (DOP) is one of the chronic complications of diabetes mellitus, but without a standardized treatment plan till now. Liuwei Dihuang pill (LDP) has gradually exerted a remarkable effect on DOP in recent years; its specific mechanism is not clear yet. METHODS:We adopted network pharmacology approaches, including multi-database search, pharmacokinetic screening, network construction analysis, gene ontology enrichment analysis, Kyoto Encyclopedia of Genes and Genomes pathway analysis and molecular docking to elaborate the active components, signaling pathways and potential mechanisms of LDP in the treatment of DOP. RESULTS:Twenty-seven active ingredients and 55 related disease targets have been found through integrated network pharmacology. Functional enrichment analysis shows that five key active ingredients, including beta-sitosterol, stigmasterol, diosgenin, tetrahydroalstonine, and kadsurenone, may give full scope to insulin secretion estrogen-level raising and angiogenesis in biological process through the pivotal targets. In addition, the underlying effect of PI3K/AKT/FOXO and VEGF pathways is also suggested in the treatment. CONCLUSION:Based on systematic network pharmacology methods, we predicted the basic pharmacological effects and potential mechanisms of LDP in the treatment of DOP, revealing that LDP may treat DOP through multiple targets and multiple signaling pathways, which provide evidence for the further study of pharmacological mechanism and broader clinical thinking.
10.1186/s13018-022-03194-2
Network pharmacology and molecular docking reveal the mechanism of Angelica dahurica against Osteosarcoma.
Medicine
Osteosarcoma (OS) is a malignant bone tumor of mesenchymal origin. Angelica dahurica is a typical traditional Chinese herb. Angelica dahurica is used in the treatment of a variety of tumors. However, the studies of Angelica dahurica for OS have not been reported. To investigate Angelica dahurica's potential mechanism of action in the treatment of OS, we used network pharmacology and molecular docking methods in this study. Of which the network pharmacology includes the collection of active ingredients of Angelica dahurica, the collection of predicted targets of Angelica dahurica and predicted targets of OS, the analysis of therapeutic targets of Angelica dahurica, gene ontology (GO) enrichment, and Kyoto encyclopedia of genes and genomes (KEGG) enrichment. The Venn plot performance showed that there were 225 predicted targets of Angelica dahurica for the treatment of OS. The therapeutic targets enrichment analysis results showed that Angelica dahurica treated OS through multiple targets and pathways. Angelica dahurica could affect OS's proliferation, apoptosis, migration, infiltration, and angiogenesis through a signaling network formed by pivotal genes crosstalking numerous signaling pathways. In addition, molecular docking results showed that sen-byakangelicol, beta-sitosterol, and Prangenin, have a relatively high potential to become a treatment for patients with OS and improve 5-year survival in OS patients. We used network pharmacology and molecular docking methods to predict the active ingredients and significant targets of Angelica dahurica for the treatment of OS and, to a certain extent, elucidated the potential molecular mechanism of Angelica dahurica in the treatment of OS. This study provided a theoretical basis for Angelica dahurica in the treatment of OS.
10.1097/MD.0000000000031055
Network pharmacology and experimental validation of Maxing Shigan decoction in the treatment of influenza virus-induced ferroptosis.
Chinese journal of natural medicines
Influenza is an acute viral respiratory infection that has caused high morbidity and mortality worldwide. Influenza A virus (IAV) has been found to activate multiple programmed cell death pathways, including ferroptosis. Ferroptosis is a novel form of programmed cell death in which the accumulation of intracellular iron promotes lipid peroxidation, leading to cell death. However, little is known about how influenza viruses induce ferroptosis in the host cells. In this study, based on network pharmacology, we predicted the mechanism of action of Maxing Shigan decoction (MXSGD) in IAV-induced ferroptosis, and found that this process was related to biological processes, cellular components, molecular function and multiple signaling pathways, where the hypoxia inducible factor-1(HIF-1) signaling pathway plays a significant role. Subsequently, we constructed the mouse lung epithelial (MLE-12) cell model by IAV-infected in vitro cell experiments, and revealed that IAV infection induced cellular ferroptosis that was characterized by mitochondrial damage, increased reactive oxygen species (ROS) release, increased total iron and iron ion contents, decreased expression of ferroptosis marker gene recombinant glutathione peroxidase 4 (GPX4), increased expression of acyl-CoA synthetase long chain family member 4 (ACSL4), and enhanced activation of hypoxia inducible factor-1α (HIF-1α), induced nitric oxide synthase (iNOS) and vascular endothelial growth factor (VEGF) in the HIF-1 signaling pathway. Treatment with MXSGD effectively reduced intracellular viral load, while reducing ROS, total iron and ferrous ion contents, repairing mitochondrial results and inhibiting the expression of cellular ferroptosis and the HIF-1 signaling pathway. Finally, based on animal experiments, it was found that MXSGD effectively alleviated pulmonary congestion, edema and inflammation in IAV-infected mice, and inhibited the expression of ferroptosis-related protein and the HIF-1 signaling pathway in lung tissues.
10.1016/S1875-5364(23)60457-1
Integrating network pharmacology and experimental validation to explore the mitophagy-associated pharmacological mechanism of modified Shisiwei Jianzhong decoction against aplastic anemia.
Biomedical chromatography : BMC
The aim of this work was to investigate the therapeutic effect of modified Shisiwei Jianzhong Decoction (SJD) on aplastic anemia (AA) and its potential pharmacological mechanism from the perspective of mitophagy. A comprehensive approach combining network pharmacology, mendelian randomization, molecular docking and animal experiments was applied to evaluate the properties of SJD against AA. By integrating multiple databases, it was determined that SJD exerted its therapeutic effect on AA by targeting three key targets [mammalian target of rapamycin (MTOR), poly(ADP-ribose) polymerase 1 (PARP1) and Sirtuin 1 (SIRT1)] through four core compounds (quercetin, resveratrol, genistein and curcumin). Mendelian randomization analysis identified MTOR as a risk factor for AA occurrence while PARP1 was a protective factor. Results of animal experiments showed that SJD improved peripheral blood counts and promoted the proliferation of hematopoietic stem cells. Mechanistically, SJD, especially at high dose, played a therapeutic role in AA by activating mitophagy-related proteins PTEN induced kinase 1 (PINK1)/Parkin and inhibiting the phosphatidylinositol 3-kinase (PI3K)/protein kinase (AKT)/MTOR pathway. This study revealed for the first time the core chemical composition of SJD and its pharmacological effects against AA, which can restore hematopoietic function by activating mitophagy. The results provide inspiration for the clinical application of traditional Chinese medicine in AA treatment.
10.1002/bmc.5963
Mechanism of Sijunzi Decoction in the treatment of colorectal cancer based on network pharmacology and experimental validation.
Journal of ethnopharmacology
ETHNOPHARMACOLOGICAL RELEVANCE:Sijunzi Decoction（SJZD）, as a famous classical prescription for the treatment of colorectal cancer(CRC) in the traditional Chinese medicine (TCM), has achieved good curative effects in clinical practice. However, its specific ingredients and molecular mechanisms is still unclear. AIM OF THE STUDY:To analyze the effective ingredients and molecular mechanisms of SJZD in the treatment of CRC through network pharmacology technology and experimental validation. MATERIALS AND METHODS:First, the TCM Systems Pharmacology database and analysis platform database were searched to screen the effective chemical components of SJZD. Swiss Target Prediction was used to predict corresponding potential target genes of compounds. After that, we constructed a components and corresponding target network by Cytoscape. Simultaneously, 5 disease databases were used to search and filter CRC targets, and then we constructed a drug-disease target protein-protein interaction (PPI) network. Cytoscape 3.7 was used for visualization and cluster analysis, and Metascape database was used for GO and KEGG enrichment analysis. We drew the main pathway-target network diagram. Autodock vina1.5.6 was applied to molecular docking for the main compounds and target proteins. Subsequently, the potential mechanism of SJZD on colon cancer predicted by network pharmacological analysis was experimentally studied and verified in vivo and in vitro. RESULTS:144 effective active chemical components, 897 potential targets, and 2584 CRC target genes were screened out. The number of common targets between the SJZD and CRC was 414.3250 GO biological process items and 186 KEGG signal pathways were obtained after analysis. The main compounds and the target protein had a good binding ability in molecular docking. The results of cell and animal experiments showed that SJZD could promote apoptosis and autophagy of CRC cells through PI3K/Akt/mTOR pathway. CONCLUSIONS:SJZD can treat CRC through multiple components, multiple targets and multiple pathways. We initially revealed the effective components and molecular mechanisms of SJZD in the treatment of CRC, and we used molecular docking and experiment for preliminary verification.
10.1016/j.jep.2022.115876
Network pharmacology, a promising approach to reveal the pharmacology mechanism of Chinese medicine formula.
Journal of ethnopharmacology
ETHNOPHARMACOLOGICAL RELEVANCE:Network pharmacology is a new discipline based on systems biology theory, biological system network analysis, and multi-target drug molecule design specific signal node selection. The mechanism of action of TCM formula has the characteristics of multiple targets and levels. The mechanism is similar to the integrity, systematization and comprehensiveness of network pharmacology, so network pharmacology is suitable for the study of the pharmacological mechanism of Chinese medicine compounds. AIM OF THE STUDY:The paper summarizes the present application status and existing problems of network pharmacology in the field of Chinese medicine formula, and formulates the research ideas, up-to-date key technology and application method and strategy of network pharmacology. Its purpose is to provide guidance and reference for using network pharmacology to reveal the modern scientific connotation of Chinese medicine. MATERIALS AND METHODS:Literatures in this review were searched in PubMed, China National Knowledge Infrastructure (CNKI), Web of Science, ScienceDirect and Google Scholar using the keywords "traditional Chinese medicine", "Chinese herb medicine" and "network pharmacology". The literature cited in this review dates from 2002 to 2022. RESULTS:Using network pharmacology methods to predict the basis and mechanism of pharmacodynamic substances of traditional Chinese medicines has become a trend. CONCLUSION:Network pharmacology is a promising approach to reveal the pharmacology mechanism of Chinese medicine formula.
10.1016/j.jep.2023.116306