Integrated Network Pharmacology and Experimental Study: Bioactive Compounds and Mechanisms of XuanTong BuLuo Decoction in Treating Diabetic Cardiomyopathy.
Jul 2026· Current pharmaceutical design· Vol 32· 0 citations
Medicine
TL;DR
It is demonstrated that XTBLD exerts cardioprotective effects against DCM via regulating its key active components, core targets (CDKN1A, IGFBP3), and related signaling pathways, providing a scientific basis for XTBLD's clinical application in DCM management.
Abstract
INTRODUCTION
Diabetic Cardiomyopathy (DCM) is a serious diabetic complication with limited therapies. While XuanTong BuLuo Decoction (XTBLD) benefits diabetic complications, its active components and anti-DCM mechanisms are unclear. This study aimed to predict XTBLD's active ingredients, key targets, and related pathways against DCM via network pharmacology, and verify them by animal experiments.
Methods
Network pharmacology and molecular docking were used to screen XTBLD's active components, potential targets against DCM, and their binding affinity. Animal experiments evaluated XTBLD's therapeutic effects on DCM by assessing glycemic control, inflammation, and key protein expression in related pathways.
Results
A total of 173 active ingredients were screened from XTBLD, with 217 intersecting genes obtained. Enrichment analysis revealed 125 signaling pathways, with 11 involved in XTBLD against DCM. Five main active components were identified using UPLC-MS/MS. In diabetic mice, XTBLD showed positive effects on blood glucose control, inflammatory response, and creatine kinase isoenzyme levels, as well as the expression of cyclin-dependent kinase inhibitor 1 and insulin-like growth factor binding protein 3.
Discussion
This study demonstrates that XTBLD exerts cardioprotective effects against DCM via regulating its key active components, core targets (CDKN1A, IGFBP3), and related signaling pathways, providing a scientific basis for XTBLD's clinical application in DCM management.
Conclusion
XTBLD may exhibits a potential protective effect on glycemic control and myocardial injury by regulating signaling pathways associated with cell growth, apoptosis, and inflammatory responses, with puerarin, luteolin, formononetin, kaempferol, and quercetin proposed as its potential main active components.
Background Diabetic nephropathy (DN) is a serious microvascular complication of diabetes that urgently requires effective treatments with low toxicity. The traditional Chinese medicine formula Yiqi Yangyin Qingre decoction (YQYYQR) has demonstrated potential in alleviating DN, yet its pharmacological mechanism remains unclear. Methods UPLC‐MS/MS combined with network pharmacology was utilized to qualitatively analyze YQYYQR′s bioactive components and predict therapeutic targets. Integrating public databases and GEO‐derived DN‐related genes, core targets were identified via intersection and subjected to pathway enrichment. Molecular docking validated key component–core target interactions, with in vivo DN mouse experiments and transcriptome sequencing performed for verification. Results This study identified 376 bioactive components from YQYYQR, corresponding to 1284 potential therapeutic targets. Cross‐analysis between these targets and DN‐related genes yielded 57 overlapping targets, among which GSK3β and NFKB1 were screened as core hub genes. Network pharmacology and transcriptomic pathway enrichment analyses indicated that the mechanism of YQYYQR in intervening DN involves biological processes such as autophagy and inflammatory response. In vivo, YQYYQR significantly improved mouse proteinuria and renal function and alleviated pathological kidney damage. Mechanistically, YQYYQR enhanced the inhibitory phosphorylation of GSK3β at Ser9, thereby facilitating TFEB nuclear translocation and activating the autophagy‐lysosomal pathway. Simultaneously, it suppresses the NLRP3/ASC/caspase‐1/GSDMD‐N–mediated pyroptosis pathway, ultimately reducing renal inflammation. Conclusion YQYYQR exerts a protective effect against DN progression by targeting core genes including GSK3β, regulating the GSK3β‐TFEB axis to restore autophagic flux via the autophagy‐lysosomal pathway, and inhibiting NLRP3‐mediated pyroptosis to mitigate excessive renal inflammation.
Shujiao Zhang, Yiran Xie, Jingyi Tang et al.· Journal of Diabetes Research· 0 citations
Diabetes retinopathy (DR) is a progressive microvascular complication of diabetes mellitus characterized by oxidative stress, inflammation, and neurovascular dysfunction. Current therapies provide limited efficacy, highlighting the need for multi-targeted, natural therapeutic alternatives.
Syzygium samarangense
(SS) is a phytochemical-rich medicinal plant with potential anti-Diabetes properties.
A data-driven systems pharmacology approach was employed to explore the anti-DR potential of
S. samarangense
phytochemicals. Twenty-nine active compounds were screened for drug-likeness using Lipinski’s Rule of Five. Overlapping targets between SS and DR were identified, yielding 403 shared targets. Network pharmacology analysis highlighted ten core proteins, including SRC, ALB, GAPDH, and TNF. Gene Ontology (GO) and KEGG pathway enrichment analyses identified key pathways such as AGE-RAGE and HIF-1 signaling. Molecular docking was performed to evaluate ligand–target interactions, followed by 500 ns molecular dynamics (MD) simulations and MM-GBSA binding free energy analysis for validation.
Docking studies identified Pinocembrin (SS5) and Stercurensin (SS4) as top-ranked ligands, with strong binding affinities toward SRC and ALB, respectively. MD simulations demonstrated superior structural stability for the SS5–SRC complex, whereas SS4–ALB exhibited moderate stability. MM-GBSA calculations further confirmed favorable binding energies, supporting their drug-like behavior. These multi-target interactions suggest that
S. samarangense
phytochemicals can modulate key DR-associated pathways.
S. samarangense
exhibits promising multi-target activity against Diabetes retinopathy. Pinocembrin (SS5) and Stercurensin (SS4) emerge as potential lead compounds for further experimental validation and drug development.
Arun Kandhan, B. Mathew, Sundarrajan Thirugnanasambandam· Frontiers in Bioinformatics· 0 citations
ETHNOPHARMACOLOGICAL RELEVANCE
Cybister chinensis Motschulsky is a traditional Chinese medicinal insect traditionally used to tonify the kidney, and clinically applied for the management of chronic kidney disease (CKD).
AIM OF THE STUDY
The present work was dedicated to identifying bioactive ingredients in the ethyl acetate fraction of C. chinensis and elucidating their mechanisms underlying the treatment of CKD.
METHODS
Compounds were isolated and used to establish fingerprints. Anti-inflammatory and anti-injury activities in vitro and grey relational analysis were applied to establish spectrum-effect relationships. Network pharmacology combined with molecular docking was employed to identify the candidate bioactive components. The effects of ethyl acetate fraction of C. chinensis were explored in doxorubicin-induced CKD rat model via Western blot, RT-PCR, transcriptomics, and metabolomics. Molecular dynamics simulation was applied to assess binding affinity of bioactive components. Cell experiments verified effects of components on inflammation, oxidative stress, and fibrosis.
RESULTS
The ethyl acetate fraction of C. chinensis was confirmed as the active fraction. Compounds 6, 10, 22, 23 and 27 were screened as the potential active components. Ethyl acetate fraction improved the condition of CKD rats, while multi-omics identified a triple-functional network against inflammation, oxidative stress, and fibrosis, with PI3K-AKT/MAPK/HIF-1 pathways verified. Cell experiments and molecular dynamics simulation identified compound 6 as the key active component, with its regulatory effects validated through PI3K-AKT/MAPK/HIF-1 pathways.
CONCLUSION
Ethyl acetate fraction of C. chinensis and its active component exerted renoprotective effects by suppressing inflammation, oxidative stress, and fibrosis in CKD via regulating PI3K-Akt, MAPK, and HIF-1 pathways.
Yun-xia Qu, Zhengze Zhang, Zhihuan Li et al.· Journal of Ethnopharmacology· 0 citations
INTRODUCTION
The global prevalence of Alcoholic Liver Disease (ALD) is rising, presenting a significant public health challenge. Taraxacum, a medicinal-food homologous plant, demonstrates hepatoprotective properties, yet its mechanisms remain unclear. This study aimed to identify the core bioactive components of Taraxacum and validate their mechanisms and therapeutic efficacy in ALD mice.
METHODS
In this study, comprehensive compositional analysis of Taraxacum was performed utilizing ultra-performance liquid chromatography coupled with UPLC-QE-MS. Active components of Taraxacum and their associated targets relevant to ALD were identified through integration of public databases. Subsequently, a Protein-Protein Interaction (PPI) network and a "Drug-components-targets" network were constructed. Key targets and key bioactive components were screened from these networks. The core component was further determined via molecular docking simulations, and its therapeutic efficacy was evaluated in the ALD mouse model by examining pertinent biochemical markers and conducting histopathological examination.
RESULTS
50 chemical components were identified from Taraxacum using UPLC-QE-MS analysis, with organic acids and flavonoids predominating. Subsequent screening via network pharmacology yielded 10 key components and 9 key targets, predominantly associated with inflammatory pathways. GO and KEGG enrichment analyses indicated significant involvement of oxidative stress responses and the HIF-1 signaling pathway, among others. Molecular docking results suggested that isorhamnetin may represent the primary active constituent against ALD, exhibiting the strongest binding affinity with MAPK3. An experiment in mouse models of alcohol-induced liver injury demonstrated that isorhamnetin significantly reduced the activities of hepatic injury markers, attenuated histopathological damage and the release of pro-inflammatory cytokines, while concurrently inhibiting oxidative stress and protecting hepatocytes.
DISCUSSION
Taraxacum therapy for ALD has the advantage of multi-component, multi-- target, and multi-pathway synergistic regulation. Comprehensive analysis demonstrated that its core component, isorhamnetin, alleviates ALD through synergistic multi-pathway mechanisms involving metabolic regulation, antioxidant defense, and anti-inflammatory effects.
CONCLUSION
This study systematically characterized the bioactive components of Taraxacum, elucidating the therapeutic efficacy of the core component, isorhamnetin, against ALD. These findings provide a scientific foundation for the development of plant- derived therapeutics targeting ALD.
Mingyu Liu, Changqing Qin, Chuanguo Liu et al.· Current Medicinal Chemistry· 0 citations
INTRODUCTION
Antipsychotic-induced hyperprolactinemia (HPRL) is a prevalent and troubling side effect that impairs treatment adherence. Xuefu Zhuyu Pills (XFZY), a traditional Chinese medicine formula, have shown efficacy in clinical practice; however, their active components and mechanisms of action remain unknown.
METHODS
We identified the components of XFZY in human plasma by UPLC-Q-TOF-MS/MS and performed network pharmacology analysis to screen key targets and core active components through topological analysis. Intersecting targets were subjected to GO and KEGG enrichment analyses on Metascape, followed by molecular docking and molecular dynamics simulations to assess binding stability between core active components and key targets.
RESULTS
A total of 67 absorbed components were found in human plasma. Based on the network pharmacology results, we identified seven core targets (AKT1, ESR1, IL6, TNF, ERBB2, CTNNB1, and MAOA) and three potential active ingredients (Makisterone B, 3-O-beta-Dglucopyranosylplatycodigenin, and 4',5,6,7-Tetramethoxyflavone). GO and KEGG suggested that hormone level regulation, the neuroactive ligand-receptor interaction, the apelin signaling pathway, and the cGMP-PKG signaling pathway may play key roles in treating HPRL caused by antipsychotic drugs.
DISCUSSION
Molecular docking results showed that the core active ingredient binds well with the key targets, and molecular dynamics simulations further verified their stability.
CONCLUSION
This study preliminarily revealed the components in human plasma of XFZY in HPRL treatment and their potential pharmacological mechanism. These findings provide a scientific basis for clinical studies.
Mingyue Liu, Zihuan Zhang, Guanli Su et al.· Combinatorial chemistry & hi...· 0 citations
Qingxin Tongmai Yin (QXTMY), a classic traditional Chinese medicine (TCM) formula widely used for cardiovascular and cerebrovascular diseases, has unclear multitarget mechanisms against atherosclerosis (AS). This study integrated network pharmacology with experimental validation to investigate these mechanisms. Network pharmacology identified 128 bioactive compounds and 135 potential targets of QXTMY, highlighting key anti‐AS targets such as TNF, IL6, insulin (INS), IL1B, MMP9, CCL2, and ALB, with the AGE‐RAGE signaling pathway as a central mechanism; principal active ingredients included quercetin, kaempferol, luteolin, and cryptotanshinone. In vitro experiments using THP‐1‐derived macrophages induced with phorbol‐12‐myristate‐13‐acetate (PMA) and oxidized low‐density lipoprotein (ox‐LDL) showed that QXTMY significantly suppressed inflammatory responses, inhibited foam cell formation, and downregulated the AGE‐RAGE signaling pathway, as measured by Western blot, ELISA, cholesterol quantification, and Nile Red staining. These findings suggest that QXTMY may exert protective effects against AS, potentially via suppression of the AGE‐RAGE‐mediated inflammatory axis. However, in vivo validation is still required to support these preliminary conclusions.
Yang Huang, Zhengshu Xia, Zhiyong Yu et al.· Mediators of Inflammation· 0 citations