Traditional Chinese Medicine Database Research Articles

Mechanism investigation of anti-NAFLD of Shugan Yipi Granule based on network pharmacology analysis and experimental verification

As a classical traditional Chinese patent medicine, Shugan Yipi Granule is widely used in China to treat non-alcoholic fatty liver disease (NAFLD) recently. Our previous study confirmed that Shugan Yipi Granule are effective in NAFLD. However, its underlying mechanism is still unknown. This study aims to investigate the mechanism of Shugan Yipi Granule on NAFLD based on network pharmacology prediction, liquid chromatography-mass spectrometry (LC-MS) analysis and in vitro verification. We obtained the active ingredients and targets of Shugan Yipi Granule and NAFLD from 6 traditional Chinese medicine databases, and the crucial components and targets screened by protein-protein interaction (PPI) network were used for molecular docking. Plasma metabolomics of NAFLD patients treated with Shugan Yipi Granule for one month was analyzed using LC-MS methods and MetaboAnalyst 4.0 to obtain significant differential metabolites and pathways. Finally, free fatty acid (FFA) induced HepG2 cells were treated with different concentrations of quercetin and kaempferol, then oil red o (ORO) and triglyceride (TG) level were tested to verify the lipid deposition of the cell. Network pharmacology analysis showed that the main active ingredients of Shugan Yipi Granule include quercetin, kaempferol and other 58 ones, as well as 188 potential targets. PI3K/Akt signaling pathway was found to be the most relevant pathway for the treatment of NAFLD. Non-targeted metabolomics showed that quercetin and kaempferol were significantly up-regulated differential metabolites and were involved in metabolic pathways such as thyroid hormone signaling. In vitro results showed that quercetin, kaempferol were effective in reducing lipid deposition and TG content by inhibiting cellular fatty acid uptake. Ultimately, with the network pharmacology and serum metabolomics analysis, quercetin and kaempferol were found to be the important active ingredients and significantly up-regulated differential metabolites of Shugan Yipi Granule against NAFLD, which we inferred that they may regulate NAFLD through PI3K/Akt signaling pathway and thyroid hormone metabolism pathway. The in vitro experiment verification results showed that quercetin and kaempferol attenuated the lipid accumulation and TG content by inhibiting the fatty acid uptake in the FFA-induced HepG2 cell. Current study provides the necessary experimental basis for subsequent in-depth mechanism research.

PTGS2 as target of compound Huangbai liquid in the nursing of pressure ulcer.

Pressure ulcer refers to ulceration and necrosis caused by local skin and cell tissues being compressed for a long time, continuous ischemia, hypoxia, and malnutrition. However, role of prostaglandin-endoperoxide synthase 2 (PTGS2) in the management of pressure ulcers in with compound Huangbai liquid is still unclear. Traditional Chinese medicine components and related targets of compound Huangbai liquid were collected through traditional Chinese medicine systems pharmacology (TCMSP) and Batman-traditional Chinese medicine database. Disease-related targets were obtained using the Gene Cards database. The protein-protein interaction (PPI) network was constructed using the Search tool for retrieval of interacting genes (STRING) and analyzed by Cytoscape to obtain the core components. To evaluate the clinical efficacy of the compound Huangbai liquid in the treatment of pressure ulcers, 40 patients with pressure ulcers were selected and divided into an observation group and a control group, with 20 individuals in each group. The observation group received treatment with compound Huangbai liquid. Sixty-five components and 480 targets of compound Huangbai liquid were obtained from TCMSP and Batman - traditional Chinese medicine databases. Two hundred seventy-three pressure ulcer-related targets were obtained. Seventy-two potential targets of compound Huangbai pigment in treatment of pressure ulcer were obtained, and 2 unrelated targets were deleted. There were 70 nodes and 1167 edges in PPI network. Gene ontology (GO) function is involved in biological processes such as reactive oxygen species metabolism and cellular response to chemical stress. Cellular components such as platelet α granules lumen and membrane rafts were involved. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment results showed that compound Huangbai liquid in treatment of pressure ulcer. The clinical results indicate that the compound Huangbai liquid has a good therapeutic effect on pressure ulcers. PTGS2 may be a target for treatment of pressure ulcers with compound Huangbai liquid, providing a new direction for its treatment.

Integrating Data Mining with Metabolomics to Analyze the Mechanism of the "Pearl-Borneol" Pair in Promoting Healing of Diabetic Wounds.

Chronic diabetic wounds pose a significant threat to the health of diabetic patients, representing severe and enduring complications. Globally, an estimated 2.5% to 15% of the annual health budget is associated with diabetes, with diabetic wounds accounting for a substantial share. Exploring new therapeutic agents and approaches to address delayed and impaired wound healing in diabetes becomes imperative. Traditional Chinese medicine (TCM) has a long history and remarkable efficacy in treating chronic wound healing. In this study, all topically applied proprietary Chinese medicines (pCMs) for wound healing officially approved by the National Medical Products Administration (NMPA) were collected from the NMPA TCM database. Data mining was employed to obtain a high-frequency TCM ingredients pair, Pearl-Borneol (1:1). This study investigated the effect and molecular mechanism of the Pearl-Borneol pair on the healing of diabetic wounds by animal experiments and metabolomics. The results from animal experiments showed that the Pearl-Borneol pair significantly accelerated diabetic wound healing, exhibiting a more potent effect than the Pearl or Borneol treatment alone. Meanwhile, the metabolomics analysis identified significant differences in metabolic profiles in wounds between the model and normal groups, indicating that diabetic wounds had distinct metabolic characteristics from normal wounds. Moreover, Vaseline-treated wounds exhibited similar metabolic profiles to the wounds from the model group, suggesting that Vaseline might have a negligible impact on diabetic wound metabolism. In addition, wounds treated with Pearl, Borneol, and Pearl-Borneol pair displayed significantly different metabolic profiles from Vaseline-treated wounds, signifying the influence of these treatments on wound metabolism. Subsequent enrichment analysis of the metabolic pathway highlighted the involvement of the arginine metabolic pathway, closely associated with diabetic wounds, in the healing process under Pearl- Borneol pair treatment. Further analysis revealed elevated levels of arginine and citrulline, coupled with reduced nitric oxide (NO) in both the model and Vaseline-treated wounds compared to normal wounds, pointing to impaired arginine utilization in diabetic wounds. Interestingly, treatment with Pearl and Pearl-Borneol pair lowered arginine and citrulline levels while increasing NO content, suggesting that these treatments may promote the catabolism of arginine to generate NO, thereby facilitating faster wound closure. Additionally, borneol alone significantly elevated NO content in wounds, potentially due to its ability to directly reduce nitrates/nitrites to NO. Oxidative stress is a defining characteristic of impaired metabolism in diabetic wounds. The result showed that both Pearl and Pearl-Borneol pair decreased the oxidative stress biomarker methionine sulfoxide level in diabetic wounds compared to those treated with Vaseline, indicating that Pearl alone or combined with Borneol may enhance the oxidative stress microenvironment in diabetic wounds. In summary, the findings validate the effectiveness of the Pearl-Borneol pair in accelerating the healing of diabetic wounds, with effects on reducing oxidative stress, enhancing arginine metabolism, and increasing NO generation, providing a mechanistic basis for this therapeutic approach.

Epigallocatechin gallate and curcumin inhibit Bcl-2: a pharmacophore and docking based approach against cancer

The protein Bcl-2, well-known for its anti-apoptotic properties, has been implicated in cancer pathogenesis. Identifying the primary gene responsible for promoting improved cell survival and development has provided compelling evidence for preventing cellular death in the progression of malignancies. Numerous research studies have provided evidence that the abundance of Bcl-2 is higher in malignant cells, suggesting that suppressing Bcl-2 expression could be a viable therapeutic approach for cancer treatment. In this study, we acquired a compound collection using a database that includes constituents from Traditional Chinese Medicine (TCM). Initially, we established a pharmacophore model and utilized it to search the TCM database for potential compounds. Compounds with a fitness score exceeding 0.75 were selected for further analysis. The Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) analysis identified six compounds with favorable therapeutic characteristics. The compounds that successfully passed the initial screening process based on the pharmacodynamic model were subjected to further evaluation. Extra-precision (XP) docking was employed to identify the compounds with the most favorable XP docking scores. Further analysis using the Molecular Mechanics Generalized Born Surface Area (MM-GBSA) method to calculate the overall free binding energy. The binding energy between the prospective ligand molecule and the target protein Bcl-2 was assessed by a 100 ns molecular dynamics simulation for curcumin and Epigallocatechin gallate (EGCG). The findings of this investigation demonstrate the identification of a molecular structure that effectively inhibits the functionality of the Bcl-2 when bound to the ligand EGCG. Consequently, this finding presents a novel avenue for the development of pharmaceuticals capable of effectively addressing both inflammatory and tumorous conditions.

Material basis and mechanism of Bletillae Rhizoma for melasma, gastrointestinal hemorrhage, lung cancer and bronchoplumonary inflammation as "homotherapy for heteropathy" based on UHPLC-Q-Exactive Orbitrap HRMS coupled with network pharmacology and molecular docking

Based on UHPLC-Q-Exactive Orbitrap HRMS coupled with the network pharmacology and molecular docking, the common material basis and molecular mechanisms of Bletillae Rhizoma for melasma, gastrointestinal hemorrhage, lung cancer and bronchoplumonary inflammation as "homotherapy for heteropathy" were explored. The fingerprint of 17 batches of Bletillae Rhizoma from different areas was established using HPLC, and the similarity analysis was carried out. The common chemical components of the 17 batches of Bletillae Rhizoma were identified using UHPLC-Q-Exactive Orbitrap HRMS. Depending on the bioavailability and drug-like properties of the common components, the active chemical components were screened, and then their protein targets were collected using the Traditional Chinese Medicine Database and Analysis Platform(TCMSP) and SwissTargetPrediction database. The protein targets related to diseases were retrieved from the databases DrugBank, TTD and GeneCards to produce a Venn diagram. The shared targets were obtained between drugs and diseases as "homotherapy for heteropathy" targets. The protein-protein interaction(PPI) was analyzed with the STRING database, and KEGG and GO analyses of the "homotherapy for heteropathy" targets were performed using the Bioconductor database. Cytoscape 3.7.2 software was employed to construct the "chemical components of Bletillae Rhizoma-homotherapy for heteropathy targets" network and PPI network, and topological analysis was conducted to screen out the key active chemical components and core targets. Finally, the affinity between the active components and core targets was evaluated using the molecular docking by AutoDock Vina 4.2.6, which verified the interaction between them. Thirteen common peaks were identified by fingerprint chromatography, and the similarity between different batches was 0.941-0.998. Fifty-three chemical components were identified by mass spectrometry in Bletillae Rhizoma, and 18 common chemical constituents were obtained in the 17 batches of Bletillae Rhizoma. Network pharmacologic screening showed that the pharmacodynamic substances of Bletillae Rhizoma for melasma, gastrointestinal hemo-rrhage, lung cancer and bronchoplumonary inflammation with "homotherapy for heteropathy" were 11 compounds, such as polysaccharides, biphenanthrenes, dihydrophenanthrenes and bibenzyls. There were 42 common targets identified for the treatment of different diseases. These targets were involved in biological processes such as cell response to chemical stress, reactive oxygen species and positive regulation of protein kinase B signal transduction. They were also involved in 121 signaling pathways, encompassing vital pathways such as PI3K-Akt, ErbB, Rap1, FoxO, MAPK and estrogen. Molecular docking results showed a strong affinity between the key active components and the core targets. This study provides a preliminary explanation of how Bletillae Rhizoma exerts its therapeutic effect on chloasma, gastrointestinal hemorrhage, lung cancer, and bronchopneumonic lesions as "homotherapy for heteropathy" through a combined action involving multiple components, targets, and pathways. These findings offer a certain theoretical basis for the further deve-lopment and application of Bletillae Rhizoma.

Resveratrol activates MAPK/ERK pathway to regulate oestrogen metabolism in type I endometrial cancer

ObjectiveEndometrial cancer (EC) is an oestrogen-dependent tumour, the occurrence of which is closely related to an imbalance of oestrogen homeostasis. Our previous studies explored the effects of Resveratrol(Res) on oestrogen metabolism. However, systematic research on the exact mechanism of action of Res is still lacking. Based on network pharmacology, molecular docking and animal experiments, the effects and molecular mechanisms of Res on endometrial cancer were investigated.MethodsThe target of Res was obtained from the high-throughput experiment and reference-guided database of TCM (HERB) and the Encyclopedia of Traditional Chinese Medicine (ETCM) databases, and the target of endometrial cancer was obtained by using the Genecards database. Venny map was used to obtain the intersection target of Res in the treatment of endometrial cancer, and the protein interaction network of the intersection target was constructed by importing the data into the STRING database. Then, the drug–disease–target interaction network was constructed based on Cytoscape 3.9.1 software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed for intersection targets using the OmicShare cloud platform. Res and core targets were analysed by molecular docking. EC model mice induced by MNNG were randomly divided into the control group, Res group, MNNG group, MNNG + Res group, and MNNG + Res + MAPK/ERKi group. The protein levels of ERK and p-ERK in the mouse uterus were detected by Western blot. The levels of E1, E2, E3, 16-epiE3, 17-epiE3, 2-MeOE1, 4-MeOE1, 2-MeOE2, 4-MeOE2, 3-MeOE1, 2-OHE1, 4-OHE1, 2-OHE2, 4-OHE2, and 16α-OHE1 in the serum and endometrial tissue of mice were measured by LC‒MS/MS.ResultsA total of 174 intersection targets of Res anti-endometrial cancer were obtained. The signalling pathways analysed by KEGG enrichment included the AGE-RAGE signalling pathway in diabetic complications, the PI3K-Akt signalling pathway and the MAPK signalling pathway. The top 10 core targets were MAPK3, JUN, TP53, CASP3, TNF, IL1B, AKT1, FOS, VEGFA and INS. Molecular docking showed that in addition to TNF, other targets had good affinity for Res, and the binding activity with MAPK3 was stable. Western blot results showed that Res increased the phosphorylation level of ERK and that MAPK/ERKi decreased ERK activation. In the LC-MS/MS analysis, the levels of 2-MeOE1, 2-MeOE2 and 4-MeOE1 in serum and uterine tissue showed a significantly decreasing trend in the MNNG group, while that of 4-OHE2 was increased (P < 0.05). The concentrations of 4-MeOE1 in serum and 2-MeOE1 and 2-MeOE2 in the endometrial tissue of mice were significantly increased after Res treatment, and those of 4-OHE2 in the serum and uterus of mice were significantly decreased (P < 0.05). Meanwhile, in the MAPK/ERKi intervention group, the effect of Res on the reversal of oestrogen homeostasis imbalance was obviously weakened.ConclusionRes has multiple targets and multiple approaches in the treatment of endometrial cancer. In this study, it was found that Res regulates oestrogen metabolism by activating the MAPK/ERK pathway. This finding provides a new perspective for subsequent research on the treatment of endometrial cancer.

Research of active compounds from Allii Macrostemonis Bulbus and potential targets against Non-Hodgkin's Lymphoma based on Network pharmacology.

Non-Hodgkin's Lymphoma (NHL) is a series of lymphoid malignancies in some aggressive subtypes with unsatisfactory treatment effects. Allii Macrostemonis Bulbus (Xie Bai) is a traditional Chinese medicine with anti-cancer activities, which may potentially suppress aggressive NHL. This study tries to discover active components and targets of Xie Bai in treating NHL by network pharmacology-based approaches. Compounds and related targets of Xie Bai were collected from the Traditional Chinese Medicine Database and Analysis Platform. Target genes associated with NHL were searched by GeneCards and DisGeNET, then the overlapped targets were further analyzed by STRING tool, GO, and KEGG pathway enrichment analysis. Molecular docking was employed to verify the interaction between compounds and targets. 11 bioactive compounds were successfully identified, with 30 targets that were screened out for the treatment of NHL. Functional enrichment analysis suggested that Xie Bai exerted its potential effects against NHL via pathways in cancer, such as PI3K/ AKT, p53, and MAPK signaling pathways. Molecular docking results showed that 3 active compounds (quercetin, beta-sitosterol, and naringenin) had good affinity with selected 6 targets（TP53, AKT1, CASP3, CCND1, HPK1, and NLRP3). Identifying six potential genes could accurately be docked with Xie Bai and had close interactions with NHL, which may provide insight into further research and new treatment strategy.

Molecular screening of phytocompounds targeting the interface between influenza A NS1 and TRIM25 to enhance host immune responses

BackgroundInfluenza A virus causes severe respiratory illnesses, especially in developing nations where most child deaths under 5 occur due to lower respiratory tract infections. The RIG-I protein acts as a sensor for viral dsRNA, triggering interferon production through K63-linked poly-ubiquitin chains synthesized by TRIM25. However, the influenza A virus's NS1 protein hinders this process by binding to TRIM25, disrupting its association with RIG-I and preventing downstream interferon signalling, contributing to the virus's evasion of the immune response. MethodsIn our study we used structural-based drug designing, molecular simulation, and binding free energy approaches to identify the potent phytocompounds from various natural product databases (>100,000 compounds) able to inhibit the binding of NS1 with the TRIM25. ResultsThe molecular screening identified EA-8411902 and EA-19951545 from East African Natural Products Database, NA-390261 and NA-71 from North African Natural Products Database, SA-65230 and SA- 4477104 from South African Natural Compounds Database, NEA- 361 and NEA- 4524784 from North-East African Natural Products Database, TCM-4444713 and TCM-6056 from Traditional Chinese Medicines Database as top hits. The molecular docking and binding free energies results revealed that these compounds have high affinity with the specific active site residues (Leu95, Ser99, and Tyr89) involved in the interaction with TRIM25. Additionally, analysis of structural dynamics, binding free energy, and dissociation constants demonstrates a notably stronger binding affinity of these compounds with the NS1 protein. Moreover, all selected compounds exhibit exceptional ADMET properties, including high water solubility, gastrointestinal absorption, and an absence of hepatotoxicity, while adhering to Lipinski’s rule. ConclusionOur molecular simulation findings highlight that the identified compounds demonstrate high affinity for specific active site residues involved in the NS1-TRIM25 interaction, exhibit exceptional ADMET properties, and adhere to drug-likeness criteria, thus presenting promising candidates for further development as antiviral agents against influenza A virus infections.

Comparative metabolomics profiling reveals the unique bioactive compounds and astringent taste formation of rosehips

Rosehips are a prominent source of numerous bioactive compounds. However, despite their extensive potential, the metabolic profiles among different rosehip species have not been fully elucidated. In this study, 523 secondary metabolites from rosehips of 12 Rosa species were identified using ultra-high-performance liquid chromatography-tandem mass spectrometry. They were primarily composed of flavonoids and phenolic acids. A K-means analysis revealed the characteristic metabolites in different rosehips. For example, R. persica contained a more abundant supply of phenolic acids, while R. roxburghii harbored a richer array of terpenoids. A total of 73 key active ingredients were screened from traditional Chinese medicine databases, and they indicated that R. persica is more promising for use in functional foods or health supplements compared with the other fruits. Moreover, a differential analysis identified 47 compounds as potential contributors to the astringent taste of rosehips, including ellagic acid 4-O-glucoside and cadaverine. This study provides valuable information to develop new functional foods of rosehips and improve the quality of their fruits.

Exploring the mechanism of Jinlida granules against type 2 diabetes mellitus by an integrative pharmacology strategy

Jinlida granule (JLD) is a Traditional Chinese Medicine (TCM) formula used for the treatment of type 2 diabetes mellitus (T2DM). However, the mechanism of JLD treatment for T2DM is not fully revealed. In this study, we explored the mechanism of JLD against T2DM by an integrative pharmacology strategy. Active components and corresponding targets were retrieved from Traditional Chinese Medicine System Pharmacology (TCMSP), SwissADME and Bioinformatics Analysis Tool for Molecular Mechanisms of Traditional Chinese Medicine Database (BATMAN-TCM) database. T2DM-related targets were obtained from Drugbank and Genecards databases. The protein–protein interaction (PPI) network was constructed and analyzed with STRING (Search Toll for the Retrieval of Interacting Genes/proteins) and Cytoscape to get the key targets. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Gene and Genomes (KEGG) enrichment analyses were performed with the Database for Annotation, Visualization and Integrated Discovery (DAVID). Lastly, the binding capacities and reliability between potential active components and the targets were verified with molecular docking and molecular dynamics simulation. In total, 185 active components and 337 targets of JLD were obtained. 317 targets overlapped with T2DM-related targets. RAC-alpha serine/threonine-protein kinase (AKT1), tumor necrosis factor (TNF), interleukin-6 (IL-6), cellular tumor antigen p53 (TP53), prostaglandin G/H synthase 2 (PTGS2), Caspase-3 (CASP3) and signal transducer and activator of transcription 3 (STAT3) were identified as seven key targets by the topological analysis of the PPI network. GO and KEGG enrichment analyses showed that the effects were primarily associated with gene expression, signal transduction, apoptosis and inflammation. The pathways were mainly enriched in PI3K-AKT signaling pathway and AGE-RAGE signaling pathway in diabetic complications. Molecular docking and molecular dynamics simulation verified the good binding affinity between the key components and targets. The predicted results may provide a theoretical basis for drug screening of JLD and a new insight for the therapeutic effect of JLD on T2DM.

Mechanism of Si Ni San Combined with Astragalus in Treating Hepatic Fibrosis: A Network Pharmacology and Molecular Docking Study.

Si Ni San combined with Astragalus (SNSQ) has demonstrated significant efficacy in the treatment of hepatic fibrosis (HF), as confirmed by clinical practice. However, its pharmacological mechanism remains unclear. This study employs network pharmacology to identify key targets and proteins for molecular docking. Additionally, animal experiments were conducted to validate the network pharmacology results, providing further insights into the mechanism of SNSQ in treating HF. Effective compounds of SNSQ were screened from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) and Encyclopedia of Traditional Chinese Medicine (ETCM) databases. Molecular formula structures of these effective compounds were obtained from the PubChem database. Partial target proteins with a probability greater than 0.6 were sourced from the SWISS database. Uniprot IDs corresponding to these target proteins were retrieved from the SUPERPRED database. The remaining target proteins of the compounds were obtained from the Uniprot database based on the Uniprot IDs. The drug target proteins were then summarized. Target points related to HF were selected from the GeneCards and OMIM databases. Common target points were identified in the Venn diagram and imported into Cytoscape 3.9.1 software to construct the "SNSQ-effective compound-target pathway-HF" network. AutoDock software was used for molecular docking of compounds and target proteins with high-degree values. The common target points underwent GO function enrichment and KEGG pathway enrichment analysis using the DAVID database. An HF rat model was established, and serum AST and ALT activities were measured. The Hyp assay kit was utilized to detect the Hyp content in liver tissue. To the transcription levels of pro-inflammatory factors (IL-1β, TNF-α, IL-6) and anti-inflammatory factors (IL-10, TGF-β1, IL-4) in rat serum and liver.IL-1β, TNF-α, IL-10, and TGF-β1 were chosen for validation through ELISA. Western blotting and qRT-PCR were used to assess the expression of related proteins, namely NFKB1, NF-κBp65, NF-κBp50, α-SMA, and Col-1 in liver tissue. qRT-PCR was also employed to study the expression of ECM synthesis and proliferation-related genes, including Cyclin D1, TIMP1, COL1A1 in HSC-T6 cells and rat liver tissue, as well as the inhibition of the ECM-related gene MMP13 in HSC-T6 cells and rat liver tissue. A total of 16 valid compounds were predicted, with kaempferol, sitosterol, and isorhamnetin exhibiting high-degree values. KEGG enrichment analysis revealed that the target genes of SNSQ were enriched in multiple pathological pathways, with the NF-Kappa B signaling pathway being predominant. Molecular docking simulations indicated strong affinities between SNSQ's primary components-kaempferol, sitosterol, isorhamnetin-and NFKB1. Experimental results demonstrated significant reductions in AST, ALT, and Hyp levels in the SNSQ group. Pro-inflammatory factors (IL-1β, TNF-ɑ) were markedly reduced, while anti-inflammatory factors (IL-10, TGF-β1) were substantially increased. The protein expression and transcription levels of α-SMA and Col-1 were significantly decreased, whereas those of NFKB1, NF-κBp65, and NF-κBp50 were notably elevated. mRNA expression levels of Cyclin D1, TIMP1, COL1A1 in HSC-T6 cells and rat liver tissue were significantly decreased, whereas MMP13 mRNA expression level was significantly increased. Treatment of HF with SNSQ involves multiple targets and pathways, with a close association with the overexpression of NFKB1 and activation of the NF-Kappa B signaling pathway. Its mechanism is closely linked to the activation of inflammatory responses, HSC activation, and proliferation.

Identification of Novel STAT3 Dimerization Inhibitor Through Structure-Based Virtual Screening for Cancer Management

Background: Signal transducer and activator of transcription 3 (STAT3) is a transcription factor that controls cell proliferation, differentiation, angiogenesis, and immunological responses. In many human malignancies, abnormal STAT3 activation promotes tumor growth via oncogenic gene expression, resulting in tumor malignancy. Many drugs with clinically authorized analogues that are used as STAT3 inhibitors for cancer therapy have several drawbacks in terms of stability and toxicity.Methods: This study used PyRx 0.8 tool to screen the Traditional Chinese Medicine (TCM) database of about 32,364 commercially available natural compounds in order to identify new STAT3 inhibitors. Physicochemical and ADME properties of selected compounds were estimated using Datawarrior and SwissADME.Result: The top 20 compounds were initially chosen based on their strong binding affinities with STAT3. Lipinski and Vaber tools were used to filter the top 20 compounds, yielding the top 6 compounds. The compounds ZINC85542844, ZINC4098720, ZINC85543599, ZINC85593523, ZINC85593528, and ZINC85593537 were passed through these filters. These compounds were found to interact with active site STAT3 residues and have several amino acid interactions in common with the control compound (STX0119).Conclusion: This study suggests that the compounds ZINC85542844, ZINC4098720, ZINC85543599, ZINC85593523, ZINC85593528, and ZINC85593537 could be used as a lead for the development of novel STAT3 inhibitors. However, further experimental validation is required to optimized them as STAT3 inhibitors.Keywords: STAT3; Transcription factor; Natural compounds; Cancer; Virtual screening

Elucidating the mechanism of action of Isobavachalcone induced autophagy and apoptosis in non-small cell lung cancer by network pharmacology and experimental validation methods

BackgroundLung cancer is the leading cause of cancer deaths, and non-small cell lung cancer (NSCLC) accounts for the majority of lung cancer-related mortality. In recent years, there have been numerous treatments for non-small cell lung cancer, but the cure and survival rates are still extremely low. Isobavachalcone (IBC) belongs to the chalcone component of the traditional Chinese medicine Psoralea corylifolia L., and is a unique Protein kinase B (AKT) pathway inhibitor with significant anticancer effects. Previous studies have shown that IBC possess a variety of biological properties, including anti-cancer, anti-inflammatory, and antioxidant properties. This study focused on the use of network pharmacology analysis, molecular docking technology and experimental validation to elucidate the potential mechanisms of IBC for the treatment of NSCLC. MethodsScreening key genes and pathways of IBC action in NSCLC using network pharmacology. The IBC target genes were from The Encyclopedia of Traditional Chinese Medicine (ETCM) and BATMAN-TCM databases, the NSCLC target genes were from GeneCards, Online Mendelian Inheritance in Man (OMIM) and The Therapeutic Target database (TTD) databases, both of which were taken as intersecting genes for protein–protein interaction network analysis and enrichment analysis, and the binding energies of the compounds to the core targets were further verified by molecular docking. Cell lines in vitro experiments were then performed to further unravel the mechanism of IBC for NSCLC. ResultsA total of 279 potential targets were retrieved by searching the intersection of IBC and NSCLC targets. Protein-protein interaction (PPI) network analysis indicated that 6 targets, including AKT1, RXRA, NCOA1, RXRB, RARA, PPARG were hub genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis suggested that IBC treatment of NSCLC mainly involves steroid binding, transcription factor activity, Pathways in cancer, cAMP signaling pathway, Adenosine 5‘-monophosphate (AMP)-activated protein kinase (AMPK) signaling pathway. Among them, the AMPK signaling pathway, which contained the largest number of enriched genes, may play a greater role in the treatment of NSCLC. Then, the results of in vitro experiment indicated that IBC could inhibit proliferation of NSCLC cells and induce cell autophagy and apoptosis. The results also showed that IBC could increase the protein expression of AMPK and decrease the protein expression of AKT and mammalian target of rapamycin (mTOR), suggesting that IBC can treat NSCLC by inducing cellular autophagy and apoptosis as well as modulating AMPK and AKT signaling pathways. ConclusionsIn summary, this study provided a new insight into the protective mechanism of IBC against NSCLC through network pharmacology and experimental validation.

The Activity, Composition and Molecular Mechanism of Bothriospermum zeylanicum (Hornem.) Fisch. Et Mey Alleviation of Nonsmall Cell Lung Cancer

Objective: To study the effect of the ethyl acetate extract of Bothriospermum zeylanicum (Hornem.) Fisch., the active ingredients and mechanism of Et Mey (EAF) in nonsmall cell lung cancer (NSCLC) were explored. Methods: 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay was used to measure the effect of EAF on the proliferation of A549, HL-60, SMMC-7721, MDA-MB-231, and SW480 tumor cells. The components were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS), and the blood components were retrieved from the constituents absorbed into the blood and metabolites of traditional Chinese medicine (DCABM-TCM) database. The mechanism was determined by network pharmacology and verified by molecular docking. Results: The IC50 values for the proliferation of tumor cell strains were 41.13, 56.72, 36.69, 48.63, and 44.48 μg/mL, respectively. A concentration of 100 μg/mL had the strongest inhibitory effect on A549 cells. A total of 33 chemical components were identified by LC-MS, 7 of which have been reported to have certain anti-NSCLC effects, and a total of 6 blood components were identified using the DCABM-TCM database. Network pharmacology analysis revealed that anti-NSCLC activity mainly involves EGFR tyrosine kinase inhibitor resistance, the PI3K-Akt signaling pathway, the AGE-RAGE signaling pathway in diabetic complications, the HIF-1 signaling pathway and the VEGF signaling pathway. The molecular docking results verified that hesperetin, luteolin, and pinocembrin bind well to the AKT1, IL6, EGFR, BCL2, and CASP3 target proteins. Conclusion: The ethyl acetate fraction of B. zeylanicum (Hornem.) Fisch. Et Mey had obvious ant-non NSCLC activity, which may be related to resistance to EGFR tyrosine kinase inhibitors and the PI3K-Akt signaling pathway in diabetic complications, and its active ingredients may be hesperetin, luteolin, and pinocembrin.

Research on the Mechanism of Traditional Chinese Medicine Treatment for Diseases caused by Human Coronavirus COVID-19

Background: Human coronaviruses are a large group of viruses that exist widely in nature and multiply through self-replication. Due to its suddenness and variability, it poses a great threat to global human health and is a major problem currently faced by the medical and health fields. background: Human coronaviruses are a large group of viruses that exist widely in nature and multiply through self-replication. Due to its suddenness and variability, it poses a great threat to global human health and is a major problem currently faced by the medical and health fields. Objective: COVID-19 is the seventh known coronavirus that can infect humans. The main purpose of this paper is to analyze the effective components and action targets of the Longyi Zhengqi formula and Lianhua Qingwen formula, study their mechanism of action in the treatment of new coronavirus pneumonia (new coronavirus pneumonia), compare the similarities and differences of their pharmacological effects, and obtain the pharmacodynamic mechanism of the two traditional Chinese medicine compounds. Method: Obtain the effective ingredients and targets of Longyi-Zhengqi Formula and Lianhua- Qingwen Formula from ETCM (Encyclopedia of Traditional Chinese Medicine) and other traditional Chinese medicine databases, use GeneCards database to obtain the relevant targets of COVID-19, and use Cytoscape software to build the component COVID-19 target network of Longyi-Zhengqi Formula and the component COVID-19 target network of Lianhua-Qingwen Formula. STRING was used to construct a protein interaction network and screen key targets. GO (Gene Ontology) was used for enrichment analysis and KEGG (Kyoto Encyclopedia of Genes and Genomes) was used for pathways to find out the targets and pathways related to the treatment of COVID-19. Results: In the GO enrichment analysis results, there are 106 biological processes, 31 cell localization and 28 molecular functions of the intersection PPI network targets of Longyi-Zhengqi Formula- COVID-19, 224 biological processes, 51 cell localization and 55 molecular functions of the intersection PPI network targets of Lianhua-Qingwen Formula-COVID-19. In the KEGG pathway analysis results, the number of targets of Longyi-Zhengqi Formula on the COVID-19 pathway is 7, and the number of targets of Lianhua-Qingwen Formula on the COVID-19 pathway is 19; In the regulation analysis results, Longyi-Zhengqi Formula achieves the effect of treating COVID-19 by regulating IL-6, and Lianhua-Qingwen Formula achieves the effect of treating pneumonia by regulating TLR4. Conclusion: This paper explores the mechanism of action of Longyi-Zhengqi Formula and Lianhua-Qingwen Formula in treating COVID-19 based on the method of network pharmacology, and provides a theoretical basis for traditional Chinese medicine to treat sudden diseases caused by human coronavirus in terms of drug targets and disease interactions. It has certain practical significance.

Targeting human progesterone receptor (PR), through pharmacophore-based screening and molecular simulation revealed potent inhibitors against breast cancer

Breast cancer, the prevailing malignant tumor among women, is linked to progesterone and its receptor (PR) in both tumorigenesis and treatment responsiveness. Despite thorough investigation, the precise molecular mechanisms of progesterone in breast cancer remain unclear. The human progesterone receptor (PR) serves as an essential therapeutic target for breast cancer treatment, warranting the rapid design of small molecule therapeutics that can effectively inhibit HPR. By employing cutting-edge computational techniques like molecular screening, simulation, and free energy calculation, the process of identifying potential lead molecules from natural products has been significantly expedited. In this study, we employed pharmacophore-based virtual screening and molecular simulations to identify natural product-based inhibitors of human progesterone receptor (PR) in breast cancer treatment. High-throughput molecular screening of traditional Chinese medicine (TCM) and zinc databases was performed, leading to the identification of potential lead compounds. The analysis of binding modes for the top five compounds from both database provides valuable structural insights into the inhibition of HPR for breast cancer treatment. The top five hits exhibited enhanced stability and compactness compared to the reference compound. In conclusion, our study provides valuable insights for identifying and refining lead compounds as HPR inhibitors.

Network pharmacology and molecular docking studies on the mechanism of action of moist exposed burn ointment for treatment of diabetic foot ulcer

Purpose: To investigate the bioactive components and mechanism of action of moist exposed burn ointment (MEBO) for treatment of diabetic foot ulcers using network pharmacology (NP) and molecular docking technology &#x0D; Methods: Through pharmacology database of traditional Chinese medicine (TCM) systems (TCMSP), analysis platform and symptom mapping (SymMap) database, the bioactive components of MEBO were screened for and protein binding to bioactive components was predicted. Proteins related to Diabetic foot ulcer (DFU) were collected from GeneCards, OMIM, PharmGkb and TTD disease databases. With R language software, the binding proteins of bioactive components of MEBO intersected with the proteins related to occurrence of DFU. Proteins of DFU linked to treatment with MEBO were subjected to analysis using gene ontology (GO) and KEGG with R language software. AutoDock and PyMOL software were employed to dock active components of MEBO and major proteins of DFU. Targeted binding potential of bioactive compounds in MEBO to core proteins of DFU was analyzed. &#x0D; Results: One hundred and five (105) bioactive ingredients and 246 likely therapeutic proteins were obtained. Proteins were mainly involved in biological processes in wound healing, oxidative stress, and lipopolysaccharide. The enriched signaling pathway focused on lipid metabolism and the process of atherosclerosis which involved PI3K and Akt, advanced glycation end-products (AGE)-receptor (RAGE) and mitogen-activated protein kinase (MAPK). The absolute values of these proteins were screened out with a docking score greater than 5 kcal/mol. &#x0D; Conclusion: The biological effects of MEBO are related to multiple proteins and multiple signaling pathways. Therefore, healing effect of MEBO on DFU occurs via multiple pathways. The biological characteristics of MEBO need to be fully elucidated in further studies.

Network pharmacology analysis and experimental validation of Xiao-Qing-Long-Tang’s therapeutic effects against neutrophilic asthma

BackgroundXiao-Qing-Long-Tang (XQLT), a classical Chinese herbal medicine formula, has been extensively used for allergic asthma treatment. However, there is limited research on its anti-inflammatory effects and mechanisms specifically in neutrophilic asthma (NA). PurposeThis study aims to investigate the potential therapeutic effects of XQLT against NA using a combination of network pharmacology and experimental validation. Study designBy utilizing traditional Chinese medicine and disease databases, we constructed an XQLT-asthma network to identify potential targets of XQLT for NA. In the experimental phase, we utilized an ovalbumin (OVA)/lipopolysaccharide (LPS)-induced model for neutrophilic asthma and examined the therapeutic effects of XQLT. ResultsOur research identified 174 bioactive components within XQLT and obtained 140 target genes of XQLT against asthma. Functional enrichment analysis revealed that these target genes were primarily associated with inflammation and cytokines. In the experimental validation, mice induced with OVA-LPS showcased eosinophilic and neutrophilic cell infiltration in peri-bronchial areas, elevated levels of IL-4 and IL-17 in both serum and lung, increased percentages of Th2 and Th17 cells in the spleen, as well as elevated levels of CD11b+ and CD103+ dendritic cells (DCs) within the lung. Treatment with XQLT effectively reduced IL-4 and IL-17 levels, decreased the percentages of Th2, Th17, CD11b+, and CD103+ DCs, and improved inflammatory cell infiltrations in lung tissues. These findings serve as a foundation for the potential clinical application of XQLT in neutrophilic asthma.

Identifying potential monkeypox virus inhibitors: an in silico study targeting the A42R protein.

Monkeypox (now Mpox), a zoonotic disease caused by the monkeypox virus (MPXV) is an emerging threat to global health. In the time span of only six months, from May to October 2022, the number of MPXV cases breached 80,000 and many of the outbreaks occurred in locations that had never previously reported MPXV. Currently there are no FDA-approved MPXV-specific vaccines or treatments, therefore, finding drugs to combat MPXV is of utmost importance. The A42R profilin-like protein of the MPXV is involved in cell development and motility making it a critical drug target. A42R protein is highly conserved across orthopoxviruses, thus A42R inhibitors may work for other family members. This study sought to identify potential A42R inhibitors for MPXV treatment using computational approaches. The energy minimized 3D structure of the A42R profilin-like protein (PDB ID: 4QWO) underwent virtual screening using a library of 36,366 compounds from Traditional Chinese Medicine (TCM), AfroDb, and PubChem databases as well as known inhibitor tecovirimat via AutoDock Vina. A total of seven compounds comprising PubChem CID: 11371962, ZINC000000899909, ZINC000001632866, ZINC000015151344, ZINC000013378519, ZINC000000086470, and ZINC000095486204, predicted to have favorable binding were shortlisted. Molecular docking suggested that all seven proposed compounds have higher binding affinities to A42R (-7.2 to -8.3 kcal/mol) than tecovirimat (-6.7 kcal/mol). This was corroborated by MM/PBSA calculations, with tecovirimat demonstrating the highest binding free energy of -68.694 kJ/mol (lowest binding affinity) compared to the seven shortlisted compounds that ranged from -73.252 to -97.140 kJ/mol. Furthermore, the 7 compounds in complex with A42R demonstrated higher stability than the A42R-tecovirimat complex when subjected to 100 ns molecular dynamics simulations. The protein-ligand interaction maps generated using LigPlot+ suggested that residues Met1, Glu3, Trp4, Ile7, Arg127, Val128, Thr131, and Asn133 are important for binding. These seven compounds were adequately profiled to be potential antivirals via PASS predictions and structural similarity searches. All seven potential lead compounds were scored Pa > Pi for antiviral activity while ZINC000001632866 and ZINC000015151344 were predicted as poxvirus inhibitors with Pa values of 0.315 and 0.215, and Pi values of 0.052 and 0.136, respectively. Further experimental validations of the identified lead compounds are required to corroborate their predicted activity. These seven identified compounds represent solid footing for development of antivirals against MPXV and other orthopoxviruses.

Functional compounds rapid screening strategy for health food function-formula-component integrated quality control by syndrome correlation-network analysis

For quality control improvement of medicine and food homology (MFH) health food, the concept of functional quality control and rapid screening strategy of functional compounds were proposed based on the dual identity characteristics. Taking Wuweisanqi Capsule as the research object, firstly, a modified method “syndrome correlation-network analysis” based on network pharmacology was used for analysis. Functions related targets were collected from common medical databases, while the clustering algorithm was used to extract the information of clinical records related to daily health care from traditional Chinese medicine (TCM) database to obtain the targets. The bioactive compounds and related targets were retrieved from the TCM Systems Pharmacology Database and Analysis Platform around the five materials included in formula. Protein-protein interaction (PPI) network and pathway enrichment analysis were performed on the intersection targets. According to the constructed formula material-compound-target-pathway network, the potential functional compounds were preliminarily identified. Secondly, key targets and compounds were analyzed by molecular docking to further screen functional compounds. Finally, combined with references, the screening and establishing determination methods of functional compounds containing total saponins, astragaloside IV, puerarin and schisandrin were finished. The rapid screening strategy adequately utilizes the advantage of TCM background for MFH health food and the effective extracting ability of massive data by the algorithm. It links three aspects of health food functions, formula materials and functional compounds, providing an efficient solution for the realization of function-formula-component integrated functional quality control, which has great application potential in health food industry.