Identification of the polyphenols from Lonicera flos-Lonicera Caulis compatibility in gut content and their implication in ameliorating gouty arthritis.

Sanmiao wan alleviates inflammation and exhibits hypouricemic effect in an acute gouty arthritis rat model

Phytochemical characterization and pharmacological mechanisms of Huazhuo Sanjie Chubi Decoction in treating gouty arthritis: A multivariant approach.

Based on network pharmacology and molecular docking methods, to explore the possible targets and mechanisms of Bidens pilosa L. in treatment of liver fibrosis. The TCMSP, GeneCard, OMIM, TTD and DrugBank databases were used to obtain the targets of Bidens pilosa L and liver fibrosis, than the intersection targets were screened out by Venny 2.1.0, the protein-protein interaction (PPI) network and the core targets were obtained by the STRING database. Use Cytoscape3.7.2 software to draw the "traditional Chinese medicine-component-target-disease" network. The DAVID database platform was explored to analyze the biological process and pathway, and predict the anti-liver fibrosis mechanism of Bidens pilosa L. AutoDock and PyMol were used to verify the molecular docking between the active ingredients of Bidens pilosa L. and the core targets. Six active components of Bidens pilosa L. and 106 intersection targets were screened. PIK3R1, HSP90AA1, SRC, TP53, AKT1, RELA and other core targets were screened by PPI network analysis. The results of GO and KEGG enrichment analysis showed that the anti-liver fibrosis of Bidens pilosa L mainly involved in the regulation and negative regulation of apoptosis process, positive regulation of protein kinase B signal transduction, positive regulation of cell migration and other biological processes. Pathways acting on cancer, fluid shear stress and atherosclerosis, lipids and atherosclerosis, PI3K-AKT signaling pathway, MAPK signaling pathway and other signaling pathways. Molecular docking showed that the active components of Bidens pilosa L. displayed good binding activity with core target proteins, and the average binding energy was -7.47 kcal/mol. The possible mechanism of the active components against liver fibrosis is to regulate the PI3K-AKT, MAPK, and other signaling pathways by acting on core targets such as PIK3R1, HSP90AA1, SRC, TP53, AKT1, RELA, and induce the apoptosis of activated HSC cells to reverse and improve liver fibrosis.

Gouty arthritis (GA) is an inflammatory joint disease caused by the deposition of monosodium urate (MSU)crystals within the joint space and surrounding tissues. In traditional Chinese medicine, Rhizoma Drynariae (Gusuibu) has long been widely used in the clinical treatment of GA, and flavonoids are considered its key bioactive constituents. This research employed network pharmacology to construct a component-target network of total flavonoids of Rhizoma Drynariae (TFRD) against GA, thereby identifying key components, core targets, and related pathways. Rat models were established by intra-articular injection of a monosodium urate crystal suspension and treated with TFRD or the positive control, colchicine, by oral gavage. After sample collection, network pharmacology-based prediction resultswere subsequently validated using rat serum metabolomics, enzyme-linked immunosorbent assay (ELISA), and Western blot analysis. Network pharmacology analysis indicated that the anti-GA effects of TFRD are mediated through key targets, including IL6, AKT1, TNF, EGFR, JUN, and PTGS2, and are mainly associated with inflammation, immune, and apoptosis-related pathways, such as the IL-17, TNF, NF-κB, MAPK, PI3K-AKT, JAK-STAT, and T-cell receptor signaling pathways. Similarly, metabolomics also uncovered the pivotal roles of the inflammatory response. Hematoxylin and eosin (H&E) staining confirmed that TFRD reduced infiltration of inflammatory cells. ELISA assay confirmed that the TFRD group significantly inhibited the expression of inflammatory factors TNF-α, IL-6, and IL-17A in synovial tissue. Western blot analysis revealed that TFRD inhibited the GA-induced hyperphosphorylation of AKT, MAPK p38, and NF-κB p65 in rat synovial tissue. TFRD can effectively ameliorate the inflammation-triggered changes in the GA rats by directly modulating related inflammatory factors and pathways.

Revealing the potential bioactive components and mechanism of Qianhua Gout Capsules in the treatment of gouty arthritis through network pharmacology, molecular docking and pharmacodynamic study strategies

Objective: Hedyotis diffusa-Scutellaria barbata herb pair (HS) has therapeutic effects on a variety of cancers, and this study aims to systematically explore the multiple mechanisms of HS in the treatment of colorectal cancer (CRC). Methods. The active ingredients of HS were obtained from TCMSP, and the potential targets related to these ingredients were screened from the STITCH, SuperPred, and Swiss TargetPrediction databases. Targets associated with CRC were retrieved by Drugbank, TTD, DisGeNET, and GeneCards. We used a Venn diagram to screen the intersection targets and used Cytoscape to construct the herb-ingredient-target-disease network, and the core targets were selected. The Go analysis and KEGG pathway annotation were performed by R language software. We used PyMol and Autodock Vina to achieve molecular docking of core ingredients and targets. Results: A total of 33 active ingredients were obtained from the HS, and 762 CRC-related targets were reserved from the four databases. We got 170 intersection targets to construct the network and found that the four ingredients with the most targets were quercetin, luteolin, baicalein, and dinatin, which were the core ingredients. The PPI analysis showed that the core targets were STAT3, TP53, MAPK3, AKT1, JUN, EGFR, MYC, VEGFA, EGF, and CTNNB1. Molecular docking results showed that these core ingredients had good binding potential with core targets, especially the docking of each component with MAPK obtained the lowest binding energy. HS acts simultaneously on various signaling pathways related to CRC, including the PI3K-Akt signaling pathway, proteoglycans in cancer, and the MAPK signaling pathway. Conclusions: This study systematically analyzed the active ingredients, core targets, and central mechanisms of HS in the treatment of CRC. It reveals the role of HS targeting PI3K-Akt signaling and MAPK signaling pathways in the treatment of CRC. We hope that our research could bring a new perspective to the therapy of CRC and find new anticancer drugs.

Background: Chlorogenic acid (CGA), a polyphenolic substance extracted from many traditional Chinese medicines, exerts a mitigative effect in dementia, including Alzheimer’s disease (AD). However, the pathological mechanisms of CGA against AD remain obscure. Objective: To elucidate the core targets, functional characteristics, and underlying mechanisms of CGA against AD using network pharmacology approaches and molecular docking technologies. Methods: GEO database was used to identify the differentially expressed genes (DEGs) in AD. PharmMpper, TargetNet, and SwissTargetPrediction predicted the CGA-related targets. STRING and Cytoscape were employed to construct and analyze the PPI network. Moreover, the Metascape platform was used to perform the GO biological processes and KEGG pathways enrichment. Molecular docking was performed using Autodock Vina software. Results: A total of 5437 targets related to AD were identified with |log2Fold Change (FC)| ≥ 1 and P < 0.05. Based on public databases, 193 putative target genes of CGA were screened. Using the Venn diagram, we found 137 co-targets between CGA and AD. According to the PPI network, 23 core targets for CGA to treat AD were obtained. KEGG enrichment displayed that the PI3K-Akt signaling pathway, MAPK signaling pathway, apoptosis, and NOD-like receptor signaling pathway were several important signaling pathways involved in CGA against AD. SRC, EGFR, HSP90AA1, MAPK1, RHOA, and PIK3R1 were hub targets associated with the activities of CGA against AD. Molecular docking analysis revealed a good binding affinity between CGA and these targets through hydrogen bonds. Conclusion: CGA might exert therapeutic effects in AD by regulating multiple targets and signaling pathways. However, further in vitro and in vivo experiments are required to thoroughly confirm the detailed targets and mechanisms of CGA against AD.

Kaempferol is a common flavonoid aglycone widely found in plants. It exhibits beneficial therapeutic effects in the treatment of arthritis. However, the effects of kaempferol on gouty arthritis (GA) have not been verified. This study aimed to explore the potential mechanisms by which kaempferol regulates GA by network pharmacology and experimental validation. Potential drug targets for GA were identified with a protein-protein interaction network. Then, we performed a KEGG pathway analysis to elucidate the major pathway involved in the kaempferol-mediated treatment of GA. In addition, the molecular docking was performed. A rat model of GA was constructed to verify the results of network pharmacology analysis and investigate the mechanism of kaempferol against GA. The network pharmacology study indicated that there were 275 common targets of kaempferol and GA treatment. Kaempferol exerted therapeutic effects on GA, in part, by regulating the IL-17, AGE-RAGE, p53, TNF, and FoxO signaling pathways. Molecular docking results showed that kaempferol stably docked with the core MMP9, ALB, CASP3, TNF, VEGFA, CCL2, CXCL8, AKT1, JUN, and INS. Experimental validation suggested that kaempferol eased MSU-induced mechanical allodynia, ankle edema, and inflammation. It significantly suppressed the expression of IL-1β, IL-6, TNF-α, and TGF-β1 and restored Th17/Treg imbalance in MSU-induced rats and IL-6-induced PBMCs. Kaempferol also affected RORγt and Foxp3 through IL-17 pathway. The present study clarifies the mechanism of kaempferol against GA and provides evidence to support its clinical use.

BackgroundJianpi Qingre Tongluo Prescription [also named Huangqin Qingrechubi Capsule (HQC)] is an empirical prescription for the treatment of gouty arthritis (GA) with excellent clinical efficacy. Mechanistically, HQC suppresses inflammation and lipid metabolism imbalance in GA by regulating long non-coding RNA H19 (lncRNA H19). Nevertheless, the detailed mechanism requires further investigation.PurposeThis study further explored the mechanism of HQC in suppressing inflammation and improving lipid metabolism via lncRNA H19 in GA.MethodsA rat model of GA was established to analyze the effects of HQC on joint injury, inflammation, and lipid metabolism in GA. Subsequently, network pharmacology was employed to identify the key pathway involved in the effects of HQC on inflammation and lipid metabolism in GA. Based on clinical and animal experimental observations, a co-culture model of GA-peripheral blood mononuclear cells and GA-fibroblast-like synoviocytes was constructed to validate the mechanism of HQC in regulating GA-related inflammation and lipid metabolism from the perspective of N6-methyladenosine (m6A) modification of lncRNA H19.ResultsHQC alleviated joint injury and improved the abnormal levels of inflammatory factors (hs-CRP, IL-4, IL-1β, and TNF-α) and lipid metabolites (TC, TG, lipoprotein, adiponectin, leptin, visfatin, and resistin) in GA rats. The IL-17 pathway was identified as an important node in HQC's effects on improving inflammation and lipid metabolism in GA. Alterations of lncRNA H19 and the IL-17 pathway were observed in GA patients and rats, which were closely correlated with inflammation and lipid metabolites. Cellular experiments revealed that high expression of lncRNA H19, attributed to ALKBH5/FTO-mediated demethylation, facilitated inflammation and lipid metabolism imbalance in GA via activating the IL-17 pathway. HQC could repress inflammation and improve lipid metabolism in GA through inhibiting the IL-17 pathway by increasing ALKBH5/FTO-mediated m6A modification of lncRNA H19; these effects might be achieved by Carthamidin.ConclusionHQC inhibited inflammation and improved lipid metabolism in GA via inactivation of the IL-17 pathway by regulating m6A modification of lncRNA H19. Our findings further support the great potential of HQC as a candidate drug for GA treatment.Graphical Supplementary InformationThe online version contains supplementary material available at 10.1186/s13020-026-01379-z.

The treatment of cognitive impairment in schizophrenia is an unaddressed need due to the absence of novel treatments. Recent studies demonstrated that fingolimod and siponimod have neuroprotective effects in several neuropsychiatric disorders; however, their pharmacological mechanisms are unclear. The objective of this study was to identify potential molecular mechanisms of fingolimod and siponimod for improving cognition of schizophrenia through network pharmacology and molecular docking. The putative target genes of ingredients, schizophrenia, and impaired cognition were obtained from online databases, including SwissTargetPrediction, PharmMapper, GeneCards, CTD, DisGeNET, and OMIM. A protein–protein interaction network was constructed to identify core targets. The DAVID database was used for GO and KEGG pathway enrichment analyses. An ingredient–target–pathway–disease network was constructed using Cytoscape. Finally, the interactions between ingredients and core targets were assessed with molecular docking. The analysis revealed 260 targets shared by fingolimod and siponimod, 257 unique targets for fingolimod, and 88 unique targets for siponimod. Two signaling pathways were involved in fingolimod-mediated improvements in the cognition of schizophrenia, including the PI3K-Akt and MAPK signaling pathways. The core targets that regulated these two pathways included IL1B, AKT1, TNF, IL6, INS, BCL2, and BDNF. The MAPK signaling pathway was involved in siponimod-mediated improvement in the cognition of schizophrenia. The MAPK pathway was regulated by three core targets, namely TNF, AKT1, and CASP3. Docking scores ranged from −5.0 to −10.4 kcal/mol. Our analysis revealed that fingolimod regulates the PI3K-Akt and MAPK signaling pathways via the core targets IL1B, AKT1, TNF, IL6, INS, BCL2, and BDNF, and siponimod regulates the MAPK signaling pathways via the core targets AKT1, TNF, and CASP3 to improve the cognition of schizophrenia. Our results provide potential targets and a theoretical basis for the design of new drugs to treat the impaired cognition of schizophrenia.

Exploring the therapeutic mechanism of curcumin in prostate cancer using network pharmacology and molecular docking

The present study explored the underlying mechanism of Astragali Radix-Curcumae Rhizoma-Paridis Rhizoma(AR-CR-PR) in the treatment of colorectal cancer(CRC) by network pharmacology and molecular docking and animal tests and verified the core targets based on the orthotopic transplantation model in nude mice. The active components of AR-CR-PR were retrieved from databases such as TCMSP. The targets of drugs and the disease were obtained from PubChem, SwissTargetPrediction, TTD, and DrugBank, and the intersection targets were imported into STRING for the analysis of the protein-protein interaction(PPI). Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) analyses were performed through DAVID. AutoDock Vina was used to perform molecular docking and binding ability prediction between the active components and the core targets. The effects of AR-CR-PR on tumor growth, metastasis, and phosphorylation of core target proteins in tumor tissues based on the orthotopic transplantation model in nude mice. As revealed by network pharmacology, AR-CR-PR contained nine core components, such as quercetin, curcumin, and β-ecdysone, and the key targets included protein kinase B(AKT1), mitogen-activated protein kinase 3(MAPK3), MAPK1, and epithelial growth factor receptor(EGFR), which was indicated that the anti-CRC effect of AR-CR-PR was presumedly achieved by regulating tumor cell proliferation, apoptosis, migration, and angiogenesis through PI3 K-AKT, MAPK and other signaling pathways. The results of molecular docking showed that the nine core components had strong binding abilities to AKT1 and MAPK3. The results in vivo showed that AR-CR-PR could reduce the volume of the orthotopic tumor, inhibit liver metastasis, and decrease the phosphorylation of AKT1 and MAPK3 in the CRC model. The mechanism of AR-CR-PR in the intervention of CRC may be related to the activation of PI3 K-AKT and MAPK signaling pathway. This study provides a scientific basis for the clinical application of AR-CR-PR in the treatment of CRC and ideas for modern research on AR-CR-PR.

Lingze mixture (LM), a traditional Chinese herbal formula, has demonstrated clinical efficacy in treating gouty arthritis (GA). However, its pharmacological mechanisms remain largely unexplored. This study aimed to conduct an exploratory investigation into the anti-inflammatory effects of LM in a GA rat model and to preliminarily identify potential signaling pathways involved through transcriptome analysis. A rat GA model was induced by monosodium urate (MSU) injection. Animals were treated with LM at low, medium, or high doses, with etoricoxib as a positive control. Synovial inflammation was assessed histologically (H&E staining). Protein expression of TLR4, MyD88, and NF-κB was detected by immunohistochemistry (IHC). To generate mechanistic hypotheses, RNA sequencing (RNA-seq) was performed on synovial tissues from the blank, model, and medium-dose LM groups. LM treatment significantly attenuated MSU-induced synovitis and dose-dependently reduced the protein levels of TLR4, MyD88, and NF-κB. Transcriptome analysis revealed significant enrichment of the TLR4/MyD88/NF-κB and MAPK signaling pathways in the model group. Notably, medium-dose LM treatment appeared to modulate these pathways, along with alanine, aspartate, and glutamate metabolism. Our findings confirm the anti-gout efficacy of LM in vivo and provide preliminary evidence suggesting its action may be associated with the modulation of the TLR4/MyD88/NF-κB pathway. This study offers valuable mechanistic clues and a foundation for further in-depth investigation into LM’s mode of action.

Oral squamous cell carcinoma (OSCC) is a tumor type with a high mortality rate. Chlorogenic acid, abundant in resources and widely utilized in cancer treatments, has seen limited studies regarding its efficacy against OSCC. This paper investigates chlorogenic acid's mechanism in treating OSCC, aiming to guide the development of novel drugs. The study employed network pharmacology, molecular docking, and survival analysis methods. Network pharmacological analysis revealed chlorogenic acid targets 23 OSCC-related proteins, including ESR1, MMP2, MMP9, SRC, MAPK8, MAPK1, CDC42, ERBB2, ATM, and BRAF. Molecular docking simulations indicated that the primary target exhibits significant binding capacity with chlorogenic acid, with MMP9 associated with tumor migration and angiogenesis standing out. Survival analysis demonstrated that the downregulation of most primary targets correlates with improved survival rates in OSCC patients. Enrichment analysis of therapeutic targets highlighted the pivotal role of MAPK-ERK and MAPK-JNK signaling pathways in chlorogenic acid's efficacy against OSCC. This paper predicts chlorogenic acid's potential targets and proposes its molecular mechanism in treating OSCC, offering a theoretical foundation for its application in OSCC treatment. We used traditional Chinese medicine, a disease pharmacology-related information base, and an analysis platform to predict targets. The Cytoscape 3.9.1 and STING databases were used to address common targets for drugs and diseases, establish networks of protein interaction relationships, and screen core targets. Meastro11.5 was used for molecular docking simulation. R4.2.2 was used for survival analysis and joint target enrichment analysis. Network pharmacological analysis identified chlorogenic acid acting on 23 OSCC targets. Molecular docking simulations revealed a strong binding affinity of chlorogenic acid compounds with these targets, particularly MMP9, essential for tumor migration and angiogenesis. Survival analysis indicated that the downregulation of most core targets was correlated with improved OSCC patient survival. Enrichment analysis of therapeutic targets highlighted the critical roles of the MAPK-ERK and MAPK-JNK signaling pathways in the effectiveness of chlorogenic acid against OSCC. This study predicted the potential targets of chlorogenic acid in OSCC treatment and hypothesized its molecular mechanism, offering a theoretical foundation for its use in OSCC therapy.

Unraveling the mechanisms of Shaoyang Shenggu decoction in treating knee osteoarthritis through mass spectrometry and bioinformatics.