The regulatory effects of Yinchen Wuling powder on chronic Hepatitis B patients with NAs by integrating network pharmacology and metabolomics: A randomized -controlled clinical study

Integrated network pharmacology, transcriptomics, and metabolomics analysis to reveal the mechanism of salt Eucommiae cortex in the treatment of chronic kidney disease mineral bone disorders via the PPARG/AMPK signaling pathway

Integration of network pharmacology and proteomics to elucidate the mechanism and targets of traditional Chinese medicine Biyuan Tongqiao granule against allergic rhinitis in an ovalbumin-induced mice model

Integrated network pharmacology, molecular docking and in vivo experiments to elucidate the extenuative mechanisms of ginseng polysaccharide against Toxoplasma gondii-induced testicular toxicity.

Background: Heart failure (HF), the final stage of cardiovascular diseases, is a clinical syndrome of cardiac structural or functional abnormalities. QiShenYiQi Dripping Pills, short for QSYQ, showed effectiveness and safety in the treatment of HF according to modern pharmacological research and clinical studies, but the mechanism remains unclear. This study aims to clarify the mechanism of QSYQ in treating heart failure through the analysis to critical biomarkers, targets and pathways.Materials and Methods: In this study, the efficacies of QSYQ in non-human primates and rodents were evaluated, and the mechanism was demonstrated by integrating network pharmacology and metabolomics analysis. Furthermore, the targets from network pharmacology and the metabolites from targeted metabolomics were jointly analyzed to screen the critical pathways.Results: In rhesus monkeys with spontaneous chronic heart failure, nasogastric administration of QSYQ for 12 weeks caused profound improvement of systolic and diastolic function as evidenced by echocardiography detection. Consistently, QSYQ administration especially with higher dose lowered the blood pressure and improved the ventricular remodeling, collagen deposition and fibrosis markedly in Spontaneous Hypertension Rats (SHR) model. Computational prediction showed that QSYQ exhibited anti-HF effects possibly through HIF-1 signaling pathway, FoxO signaling pathway, TNF signaling pathway, PI3K-Akt signaling pathway and other enriched paths. Metabolomics analysis obtained 23 significantly altered metabolites, revealing that QSYQ significantly regulated the abnormal levels of fatty acids, carnitines, organic acids pyridines, nucleosides, which were mostly involved in myocardial energy metabolism related pathways.Conclusion: Based on serum and myocardium metabolomics and network pharmacology, the present study revealed that the actions of QSYQ in treating HF depend on multi-components, multi-targets and multi-pathways.

EASL Recognition Awardee 2013: Professor Yun-Fan Liaw

Integrated network pharmacology and metabolomics to investigate the effects and possible mechanisms of Dehydroevodiamine against ethanol-induced gastric ulcers

Evidence of the benefits of cordycepin (Cpn) for treating obesity is accumulating, but detailed knowledge of its therapeutic targets and mechanisms remains limited. This study aimed to systematically identify Cpn's therapeutic targets and pathways in Western diet (WD)-induced obesity using integrated network pharmacology, transcriptomics, and experimental validation. A Western diet (WD)-induced mice model was used to evaluate the effectiveness of Cpn in ameliorating obesity. A network pharmacology analysis was then employed to identify the potential anti-obesity targets of Cpn. GO functional enrichment and KEGG pathway analysis were performed to elucidate the potential functions of the identified targets, followed by constructing a protein-protein interaction network to screen the core targets. Meanwhile, quantitative transcriptomics was conducted to validate and broaden the network pharmacology findings. Finally, molecular docking and quantitative real-time PCR assay were used for the core target validation. Cpn treatment effectively alleviated obesity-related symptoms in WD-induced mice. The metabolic pathway, insulin signaling pathway, HIF-1 signaling pathway, FoxO signaling pathway, lipid and atherosclerosis pathway, and core targets including CPS1, HRAS, MAPK14, PAH, ALDOB, AKT1, GSK3B, HSP90AA1, BHMT2, EGFR, CASP3, MAT1A, APOM, APOA2, APOC3, and APOA1 are involved in regulating the therapeutic effect of Cpn. This study comprehensively uncovers the potential mechanism of Cpn against obesity based on network pharmacology and quantitative transcriptomics, which provides evidence for revealing the pathogenesis of obesity, suggesting that Cpn is a possible lead compound for anti-obesity treatment.

Objective Bushen Huoxue Huatan Decoction (BHHD) is a classic prescription for treating polycystic ovary syndrome (PCOS). This study aims to explore the effects and possible mechanisms of BHHD on PCOS by integrating network pharmacology and clinical study. Methods The components and potential drug targets of BHHD were analysed using the TCMSP platform, and the potential pathogenesis targets for PCOS were analysed using the GeneCards and OMIM databases. Subsequently, a disease-compound-target network diagram was established to identify the targets of BHHD treatment on PCOS. In addition, protein-protein interaction analysis, KEGG pathway analysis, and Gene Ontology biological analysis were carried out to reveal the mechanisms of BHHD. To further validate the analysis, a clinical trial involving 62 PCOS patients was conducted. All patients were treated with BHHD for 3 months and the ovulation rate, anthropometric indicators, clinical symptoms, and serological indicators were measured and compared before and after treatment. Results The network pharmacology analysis showed that quercetin, luteolin, and kaempferol are the most significant active components in BHHD; STAT3, Jun, AKT1, MAPK3, MAPK1, and TP53 are the most critical drug targets; regulating hormones, reversing insulin (INS) resistance, exerting anti-inflammatory effects, and improving fertility might be the most important mechanisms of BHHD in the treatment of PCOS. After BHHD administration, the cyclic ovulation rate and the clinical symptoms including acanthosis nigricans and acne of patients were obviously improved. The serum endocrine levels of luteinising hormone (LH), LH/follicle-stimulating hormone, testosterone, dehydroepiandrosterone sulphate, insulin (INS), and area under the INS curve were evidently reversed, and the serum inflammatory factors levels including human interleukin (IL)-18, IL-16, IL-1β, IL-8, macrophage migration inhibitory factor, and human leukocyte differentiation antigen CD40 ligand were greatly reduced. Conclusion BHHD has a good therapeutic effect on PCOS, and its mechanisms may be related to regulating hormone levels, improving insulin resistance, alleviating inflammation, and promoting pregnancy.

Chapter 1: Prevention

Network pharmacology and transcriptomics to determine Danggui Yifei Decoction mechanism of action for the treatment of chronic lung injury

Le-Cao-Shi (LCS) has long been used as a folk traditional Chinese medicine formula against liver injuries, whereas its pharmacological mechanisms remain elusive. Our study aims to investigate the underlying mechanism of LCS in treating liver injuries via integrated network pharmacology, metabonomics, and experimental validation. By network pharmacology, 57 compounds were screened as candidate compounds based on ADME parameters from the LCS compound bank (213 compounds collected from the literature of three single herbs). According to online compound–target databases, the aforementioned candidate compounds were predicted to target 87 potential targets related to liver injuries. More than 15 pathways connected with these potential targets were considered vital pathways in collectively modulating liver injuries, which were found to be relevant to cancer, xenobiotic metabolism by cytochrome P450 enzymes, bile secretion, inflammation, and antioxidation. Metabonomics analysis by using the supernatant of the rat liver homogenate with UPLC-Q-TOF/MS demonstrated that 18 potential biomarkers could be regulated by LCS, which was closely related to linoleic acid metabolism, glutathione metabolism, cysteine and methionine metabolism, and glycerophospholipid metabolism pathways. Linoleic acid metabolism and glutathione metabolism pathways were two key common pathways in both network pharmacology and metabonomics analysis. In ELISA experiments with the CCl4-induced rat liver injury model, LCS was found to significantly reduce the levels of inflammatory parameters, decrease liver malondialdehyde (MDA) levels, and enhance the activities of hepatic antioxidant enzymes, which validated that LCS could inhibit liver injuries through anti-inflammatory property and by suppressing lipid peroxidation and improving the antioxidant defense system. Our work could provide new insights into the underlying pharmacological mechanisms of LCS against liver injuries, which is beneficial for its further investigation and modernization.

BackgroundPolygala tenuifolia Willd (PT) is a plant with both medicinal and edible values. Traditionally, it has been used for sedation, enhancing cognition, resolving phlegm, and relieving cough. However, its protective effects and mechanisms against chronic obstructive pulmonary disease (COPD) remain unclear.Aim of the studyThis study aims to observe the protective effects of the water extract of Polygala tenuifolia Willd (WEPT) on COPD, and to preliminarily elucidate its potential therapeutic mechanisms by integrating network pharmacology, molecular docking, multi-omics analysis, and molecular experiments.Methods and materialsHPLC quantified WEPT constituents. COPD mice models established via chronic smoke exposure underwent WEPT treatment, and the therapeutic effect was evaluated by lung function test, histopathology and cytokine profiling. Integrated multi-omics analyses (network pharmacology, transcriptomics, microbiomics) identified bioactive compounds, therapeutic targets, pathway regulations, and microbiota dynamics. Molecular docking validated compound-target interactions, while immunohistochemical/fluorescence assays confirmed key protein expression in lung tissues.ResultsWEPT administration effectively reduced inflammatory cytokine levels in COPD mice, improved lung function, and alleviated histopathological damage like alveolar structural injury and airway inflammation. Network pharmacology and transcriptomic analyses identified Norhyoscyamine and Onjixanthone I as key active components, targeting PIK3CA and AKT1 via PI3K-AKT pathway regulation. Microbiome analysis showed WEPT restored gut microbiota balance. Molecular docking confirmed strong binding of bioactive compounds to core targets, while immunostaining assays demonstrated WEPT suppressed p-PI3K and p-AKT protein expression.ConclusionWEPT may exert its intervention effects on COPD through a multi-target and multi-level comprehensive regulatory mechanism.

BackgroundChronic gastritis (CG) significantly impacts patients’ quality of life and can progress to more severe gastric conditions. In China, Traditional Chinese Medicine (TCM) has been widely applied for its holistic efficacy in treating chronic superficial gastritis (CSG), including formulas like Jinhong Tablets (JHT), known for their anti-inflammatory effects. However, the mechanism of action of JHT in treating CSG still requires further clarification.PurposeThis study aimed to elucidate the mechanism by which JHT alleviates CSG, integrating network pharmacology, untargeted metabolomics, and gut microbiota analyses.MethodsThe CSG rat model was established, and treatment effects were assessed via Hematoxylin and eosin (H&E) staining. The target profiles of JHT’s components and the holistic targets of JHT were obtained. Enrichment analyses were performed on holistic targets and a multi-layer biomolecular network of JHT was established. The study also analyzed rat plasma for differential metabolites through untargeted metabolomics and evaluated the diversity and composition of gut microbiota in fecal and cecal contents samples using 16S rRNA sequencing.ResultsJHT effectively reduced gastric inflammation in CSG rats. Network pharmacology indicated that diverse metabolic processes including lipid metabolism and nitric oxide metabolism play pivotal roles in the therapeutic effects of JHT on CSG. Metabolomics analysis identified differential metabolites, including betaine, which help enrich the gut microbiota. Phospholipids and citrulline indicate the severity of CSG. The pathway enrichment of differential metabolites confirmed the network pharmacology results and indicated the association with the gut microbiota. Through gut microbiota analyses, it was discovered that JHT could augment the gut microbiota by enhancing the abundance of betaine. Additionally, JHT was shown to boost the production of short-chain fatty acids (SCFAs) by increasing the abundances of Faecalibaculum and Bifidobacterium, consequently alleviating gastric inflammation in CSG.ConclusionOur study revealed that JHT alleviated CSG through diverse metabolic processes including lipid and energy metabolism. Metabolites such as betaine, along with gut microbiota including Faecalibaculum and Bifidobacterium, play crucial roles in the therapeutic interventions. Our findings support the therapeutic potential of JHT and contribute to a deeper understanding of the role of TCM in the treatment of CSG.Graphical

Asiatic acid alleviates liver fibrosis via multiple signaling pathways based on integrated network pharmacology and lipidomics

Integrated network pharmacology, metabolomics and molecular docking analysis to reveal the mechanisms of quercetin in the treatment of hyperlipidemia