Analysis of the Potential Angiogenic Mechanisms of BuShenHuoXue Decoction against Osteonecrosis of the Femoral Head Based on Network Pharmacology and Experimental Validation.

OBJECTIVE: Osteonecrosis of the femoral head (ONFH) is a common orthopedic disease with a high disability rate. The clinical effect of BuShenHuoXue decoction (BSHX) for ONFH is satisfactory. We aimed to elucidate the potential angiogenic mechanisms of BSHX in a rat femoral osteonecrosis model and bone marrow mesenchymal stem cells (BMSCs). METHODS: With in vivo experiments, we established the steroid-induced osteonecrosis of the femoral head (SONFH) model using Sprague-Dawley (SD) rats (8-week-old). The rats were randomly divided into five group of 12 rats each and given the corresponding interventions: control, model (gavaged with 0.9% saline), BSHX low-, medium- and high-dose groups (0.132 3, 0.264 6, and 0.529 2 g/mL BSHX solution by gavage). After 12 weeks, haematoxylin and eosin (H&E) staining was preformed to evaluate rat osteonecrosis. the expression of angiogenic factors (CD31, VEGFA, KDR, VWF) in rat femoral head was detected by immunohistochemistry, qPCR and western blotting. In cell experiment, BMSCs were isolated and cultured in the femoral bone marrow cavity of 4-week-old SD rats. BMSCs were randomly divided into eight groups and intervened with different doses of BSHX-containing serum and glucocorticoids: control group (CG); BSHX low-, medium-, and high-dose groups (CG + 0.661 5, 1.323, and 2.646 g/kg BSHX gavage rat serum); dexamethasone (Dex) group; and Dex + BSHX low-, medium-, and high-dose groups (Dex + 0.661 5, 1.323, and 2.646 g/kg BSHX gavaged rat serum), the effects of BSHX-containing serum on the angiogenic capacity of BMSCs were examined by qPCR and Western blotting. A co-culture system of rat aortic endothelial cells (RAOECs) and BMSCs was then established. Migration and angiogenesis of RAOECs were observed using angiogenesis and transwell assay. Identification of potential targets of BSHX against ONFH was obtained using network pharmacology. RESULTS: BSHX upregulated the expression of CD31, VEGFA, KDR, and VWF in rat femoral head samples and BMSCs (p < 0.05, vs. control group or model group). Different concentrations of BSHX-containing serum significantly ameliorated the inhibition of CD31, VEGFA, KDR and VWF expression by high concentrations of Dex. BSHX-containing serum-induced BMSCs promoted the migration and angiogenesis of RAOECs, reversed to some extent the adverse effect of Dex on microangiogenesis in RAOECs, and increased the number of microangiogenic vessels. Furthermore, we identified VEGFA, COL1A1, COL3A1, and SPP1 as important targets of BSHX against ONFH. CONCLUSION: BSHX upregulated the expression of angiogenic factors in the femoral head tissue of ONFH model rats and promoted the angiogenic capacity of rat RAOECs and BMSCs. This study provides an important basis for the use of BSHX for ONFH prevention and treatment.

The potential of traditional herbal active ingredients in the treatment of sarcopenia animal models: focus on therapeutic effects and mechanisms.

Sarcopenia is a major global public health problem that harms individual physical function. In 2018, the European Working Group on Sarcopenia in the Elderly 2 classified sarcopenia into primary and secondary sarcopenia. However, information on the pathogenesis and effective treatment of primary and secondary sarcopenia is limited. Traditional herbal active ingredients have biological activities that promote skeletal muscle health, showing potential preventive and therapeutic effects on sarcopenia. Therefore, this narrative review aims to provide a comprehensive overview of global traditional herbal active ingredients' beneficial therapeutic effects and molecular mechanisms on sarcopenia-related animal models. For this purpose, we conducted a literature search in three databases, PubMed, Web of Science, and Embase, consistent with the review objectives. After the screening, 12 animal studies met the review themes. The review results showed that the pathological mechanisms in sarcopenia-related animal models include imbalanced protein metabolism, oxidative stress, inflammation, apoptosis, insulin resistance, endoplasmic reticulum stress, impaired mitochondrial biogenesis, and autophagy-lysosome system aggravation. Eleven traditional herbal active ingredients exerted positive anti-sarcopenic effects by ameliorating these pathological mechanisms. This narrative review will provide meaningful insight into future studies regarding traditional herbal active ingredients for treating sarcopenia.

A severe case of rhabdomyolysis after Moderna mRNA anti-COVID-19 vaccine with a literature review.

The identification of rhabdomyolysis as a potential fatal adverse reaction to recent COVID-19 vaccines is essential. As the symptoms of rhabdomyolysis are not specific, the threshold to actively search for this complication should be low.

Potential of natural medicines for treatment of osteoporosis: a narrative review.

OBJECTIVE: To organize the fragmented information available in the literature to describe and summarize the extracts used by natural medicines in the treatment of bone loss, and to provide evidence and support for the potential use of natural medicines in the treatment of osteoporosis. METHODS: A literature survey for relevant information regarding the osteogenesis of Dongkuiguo (), Machixian (). etc., was conducted using PubMed, ScienceDirect, MEDLINE, Springer LINK and Google Scholar electronic databases from the years 2000-2020. RESULTS: Dongkuiguo (), Machixian (). etc., both inhibit the activity of osteoclasts and reduce bone resorption by regulation of signaling pathways through interacting with signaling molecules. CONCLUSIONS: In this review, the current knowledge of the novel medicines with osteogenesis properties were summarized and their potential in the treatment of bone loss were demonstrated, but the lack of research on the regulation of the signaling pathway's mechanism of action, and the corresponding theoretical basis for the application of natural medicines in clinical osteoporosis, made it difficult to be widely applied and promoted in clinical practice. Further experiments with some of the medicines and the mechanisms is needed to realize their potential as osteoporosis treatments.

Recent advances in ginsenosides against respiratory diseases: Therapeutic targets and potential mechanisms.

BACKGROUND: Respiratory diseases mainly include asthma, influenza, pneumonia, chronic obstructive pulmonary disease, pulmonary hypertension, lung fibrosis, and lung cancer. Given their high prevalence and poor prognosis, the prevention and treatment of respiratory diseases are increasingly essential. In particular, the development for the novel strategies of drug treatment has been a hot topic in the research field. Ginsenosides are the major component of Panax ginseng C. A. Meyer (ginseng), a food homology and well-known medicinal herb. In this review, we summarize the current therapeutic effects and molecular mechanisms of ginsenosides in respiratory diseases. METHODS: The reviewed studies were retrieved via a thorough analysis of numerous articles using electronic search tools including Sci-Finder, ScienceDirect, PubMed, and Web of Science. The following keywords were used for the online search: ginsenosides, asthma, influenza, pneumonia, chronic obstructive pulmonary disease (COPD), pulmonary hypertension (PH), lung fibrosis, lung cancer, and clinical trials. We summarized the findings and the conclusions from 176 manuscripts on ginsenosides, including research articles and reviews. RESULTS: Ginsenosides Rb1, Rg1, Rg3, Rh2, and CK, which are the most commonly reported ginsenosides for treating of respiratory diseases, and other ginsenosides such as Rh1, Rk1, Rg5, Rd and Re, all primarily reduce pneumonia, fibrosis, and inhibit tumor progression by targeting NF-κB, TGF-ß/Smad, PI3K/AKT/mTOR, and JNK pathways, thereby ameliorating respiratory diseases. CONCLUSION: This review provides novel ideas and important aspects for the future research of ginsenosides for treating respiratory diseases.

Network pharmacology-based prediction of potential effective components of traditional Chinese medicine and their molecular mechanisms of action in the anti-angiogenic treatment of Kaposi′s sarcoma / 中华皮肤科杂志

Objective:To investigate potential effective components of traditional Chinese medicine and their molecular mechanisms of action in the anti-angiogenic treatment of Kaposi′s sarcoma based on network pharmacology, and to predict key targets and signal pathways in the anti-angiogenic treatment of Kaposi′s sarcoma with traditional Chinese medicine.Methods:According to the previous network pharmacology-based analysis results, main chemical components and targets of Rhizoma Polygoni Cuspidati, Cortex Mori, Rhizoma Smilacis Glabrae and Fructus Perillae were obtained by using the traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP); potential therapeutic targets for angiogenesis and Kaposi′s sarcoma were obtained by searching the GeneCard, OMIM, DrugBank and TTD databases, and a Venn diagram was constructed to obtain targets for the interaction between Kaposi′s sarcoma and anti-angiogenic drug components; a protein-protein interaction model was constructed using the STRING 11.5 platform; the Cytoscape 3.6.0 software was used to construct the component-target visual network. Meanwhile, the Metascape platform was used to analyze the Gene Ontology (GO) functions and the enrichment of Kyoto Encyclopedia of Genes and Genome (KEGG) -based pathways. The main active ingredients and core targets obtained through the above analyses were then verified by molecular docking. Results:The core components of anti-Kaposi′s sarcoma angiogenesis drugs were resveratrol (degree: 142), quercetin (degree: 141), kaempferol (degree: 56), luteolin (degree: 56), β-sitosterol (degree: 37), arachidonic acid (degree: 36), naringenin (degree: 36), etc., and the core target was prostaglandin-endoperoxide synthase 2 (PTGS2). KEGG analysis revealed that the cancer signaling pathways were the important pathways related to the inhibiton of angiogenesis in Kaposi′s sarcoma; functional enrichment analysis showed that the positive regulation of cell migration was the most significantly enriched GO term in the biological process category. Molecular docking results showed that resveratrol, quercetin, kaempferol and luteolin had good affinity with PTGS2, especially quercetin and luteolin exhibited the strongest binding abilities to PTGS2, with the binding energies being -9.4 and -9.5 kcal/mol, respectively.Conclusion:This study showed that the 4 traditional Chinese medicines recorded in TCMSP (including Rhizoma Polygoni Cuspidati., Cortex Mori, Rhizoma Smilacis Glabrae and Fructus Perillae) may play an anti-angiogenic role by regulating cancer signaling pathways and acting on targets such as PTGS2, and predicted the possible anti-angiogenesis mechanisms of traditional Chinese medicines in Kaposi′s sarcoma.

Study on the mechanism of Kangmin Zhisou Granules in the treatment of bronchial asthma based on network pharmacology and animal experiments / 国际中医中药杂志

Objective:To deeply explore the potential mechanism of Kangmin Zhisou Granules in the treatment of bronchial asthma through network pharmacology method; To verify it with animal experiments.Methods:The active components and corresponding target information of Kangmin Zhisou Granules were screened with the help of BATMAN-TCM database, and the related disease targets of bronchial asthma were obtained through GeneCards and OMIM databases. The drug targets and bronchial asthma targets were intersected and imported String database was used to establish PPI network. Cytoscape 3.9.1 software was used to draw the network diagram of "Chinese materia medica-active components-intersection targets" and the core targets were screened. GO and KEGG enrichment analysis was performed on the core targets using DAVID database. A mouse model of asthma induced by ovalbumin was prepared. After the intervention of Kangmin Zhisou Granules, the pathological changes of mouse lung tissue were observed, and the contents of serum TNF-α, IL-6, IL-1 β were detected by ELISA.Results:Totally 240 active components and 1 364 potential targets were obtained from Kangmin Zhisou Granules. Tumor necrosis factor (TNF), interleukin-6 (IL-6), protein kinase B (AKT1), albumin (ALB), interleukin 1-beta (IL-1β) and other 11 core targets were obtained after screening. The results of GO enrichment analysis showed that the treatment of bronchial asthma by Kangmin Zhisou Granules mainly involved the positive regulation of protein phosphorylation, the regulation of inflammatory response, lipopolysaccharide response and other biological processes, as well as TNF, activated protein kinase (MAPK), interleukin-17 (IL-17) and other signaling pathways. Animal experiments confirmed that Kangmin Zhisou Granules could reduce the expression levels of TNF-α, IL-6 and IL-1β in serum ( P<0.05), and reduce the infiltration of inflammatory cells in the lung tissue of mice, thereby relieving asthma symptoms. Conclusion:Kangmin Zhisou Granules may exert anti-inflammatory effects by acting on TNF-α, IL-6, IL-1β and other targets to alleviate asthma symptoms.

Discussion on the anti-tumor metastasis mechanism of Notoginseng Radix et Rhizoma based on internet pharmacology / 国际中医中药杂志

Objective:To analyze and explore the possible mechanism of anti-tumor metastasis of Notoginseng Radix et Rhizoma using Internet pharmacology. Methods:The active components and targets of Notoginseng Radix et Rhizoma were screened by retrieving Chinese Medicine System Pharmacology Database and Analysis Platform (TCMSP). GeneCards database was used to screen the anti-tumor metastasis-related targets, and compounds and disease targets were under mapping analysis. Key targets of Notoginseng Radix et Rhizoma for anti-tumor metastasis were screened through Venn map. With the help of Cytoscape 3.7.2 software, a compound-disease network diagram was constructed. String platform was used to build a PPI network. Bioconductor was used to enrich the target genes for KEGG signaling pathway and GO biological process analysis. Results:Totally 119 active components were selected from Notoginseng Radix et Rhizoma. There were 8 eligible active components, corresponding to 162 related targets, 121 targets related to anti-tumor metastasis, and 30 key targets screened by PPI network, including AKT1, MAPK1, JUN, RELA, IL6, etc. GO enrichment analysis mainly involved biological processes such as cytokine receptor binding, heme binding, RNA polymerase Ⅱ transcription factor binding, ubiquitin protein ligase binding, and steroid hormone receptor activity. 149 signal pathways related to Notoginseng Radix et Rhizoma anti-tumor metastasis were obtained by KEGG enrichment analysis, mainly involving multiple signal pathways, such as AGE-RAGE and PI3K-Akt, and hepatitis B, Kaposi's sarcoma-associated herpes virus infection, human cytomegalovirus infection and other viral infections and various tumors. Conclusion:Notoginseng Radix et Rhizoma can pass multiple active components, such as ginsenoside f2, ginsenoside rh2 β-, sitosterol, stigmasterol and quercetin, and multiple targets, such as AKT1, MAPK1, JUN, RELA and IL6, acting on multiple pathways such as PI3K-Akt, thereby playing the role of anti-tumor metastasis.

Study on the mechanism of Kechuan'an Oral Liquid for the treatment of asthma / 国际中医中药杂志

Objective:To explore the mechanism of Kechuan'an Oral Liquid in treating asthma based on network pharmacology; To carry out experimental verification.Methods:The effective components and targets of Kechuan'an Oral Liquid were obtained through TCMSP and literature search. The related targets of asthma were screened by GEO database, and the intersection targets of drug and disease were selected. The PPI network was constructed by STRING database, and the GO function and KEGG pathway were enriched and analyzed for key targets by DAVID database. The rats were divided into blank control group, model group and Kechuan'an Oral Liquid group according to the method of random number table. Kechuan'an Oral Liquid group received Kechuan'an Oral Liquid 12.34 ml/kg for gavage, and blank control group and model group were perfused with distilled water of the same volume for gavage, once a day for 3 days. The asthma model of rats was prepared by atomizing the mixture of acetylcholine chloride and histamine phosphate, and HE staining was used to observe the pathological changes of lung tissue; Western blot was used to detect the protein expressions of IL-6, TLR4, MyD88 and TAK1, and the network pharmacological prediction results were verified.Results:A total of 153 active components, 1 896 targets and 2 982 differentially expressed genes of Kechuan'an Oral Liquid were screened out, and 25 intersection targets of drugs and diseases were obtained. The enrichment results showed that toll-like receptor signaling pathway, TNF signaling pathway and Nod-like receptor signaling pathway were the main mechanisms of immune inflammation. Compared with the control group, the lung tissue of rats in the model group showed morphological changes such as thickening of air duct wall and infiltration of inflammatory cells, which were significantly improved in the Kechuan'an Oral Liquid group. Compared with the control group, the expressions of IL-6, TLR4, MyD88 and TAK1 in the model group significantly increased ( P<0.01), and compared with model group, the expressions of IL-6, TLR4, MyD88 and TAK1 in Kechuan'an Oral Liquid group significantly decreased ( P<0.05 or P<0.01). Conclusion:Kechuan'an Oral Liquid can inhibit toll-like receptor signaling pathway and mediate anti-inflammatory effect to treat asthma.

Discussion on mechanism and experimental verification of Herba Hedyotidis in treating liver fibrosis based on network pharmacology / 国际中医中药杂志

Objective:To study the mechanism of Herba Hedyotidis against liver fibrosis based on network pharmacology. Methods:Based on TCMSP database and Uniprot database, the effective components and target genes of Herba Hedyotidis were screened. Target genes of liver fibrosis were screened by GeneCards and OMIM database, and the "disease-component-target" network map was constructed by Cytoscape 3.8.2 software. Protein interaction network was constructed by STRING database, and the Cytoscape 3.8.2 software was used to screen the core target out. The core targets were analyzed by gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Experimental verification was performed to the analysis results. A hepatic fibrosis model was established by intraperitioneal imjection of 40% carbon tetrachloride oil solution in rats that were then divided into the model control group and the Herba Hedyotidis group by randomized number table table, with 10 rats in each group. Ten normal rats were used as the normal control group. The Herba Hedyotidis group were injected 2.7 g/kg herb aqueous extract by intragastric administration, once a day, for 4 weeks; and the normal and model control group were given the same volume distilled water for gavage. The serum GPT, GOT, Alb and liver pathologic changes were observed. The serum expressions of IL-6, IL-1β and TGF-β1 were detected by ELISA. The expressions of PI3K, Akt, HIF-1α and VEGF were detected by Western blot. Results:5 effective components and 118 targets of Herba Hedyotidis in the treatment of hepatic fibrosis were obtained. Stigmasterol, β-sitosterol and quercetin were the most effective components with high moderate value. The moderate targets were VEGF, EGFR, HIF-1α and IL-6. The core genes of PPI network were HIF-1α, IL-6, etc. GO enrichment analysis showed that RNA transcription, protein binding and other processes may be affected. KEGG pathway enrichment analysis showed that significant enrichment pathways were cancer pathway, hepatitis B pathway, PI3K/Akt, HIF pathway and so on. Animal experimental results showed that compared with model group, liver histopathology was improved significantly, the content of GPT, GOT, IL-6, IL-1β and TGF-β1 decreased ( P<0.01), the content of Alb increased ( P<0.01), and the protein expressions of PI3K, Akt, HIF-1α and VEGF in liver tissue were down-regulated ( P<0.01). Conclusion:The Herba Hedyotidis exerts functions of anti-hepatic fibrosis through acting on the targets of VEGF, EGFR, HIF-1α and IL-6, regulating the PI3K/Akt, HIF-1 pathways, and has anti-inflammatory, anti-angiogenesis, anti-tumor and other biological functions.

Molecular mechanism of Danggui Niantong Decoction in the treatment of gouty arthritis based on network pharmacology and molecular docking / 国际中医中药杂志

Objective:To explore the molecular mechanism of Danggui Niantong Decoction in the treatment of gouty arthritis (GA) based on network pharmacology and molecular docking.Methods:By selecting for the active components and targets of Danggui Niantong Decoction with TCMSP, and retrieving the GeneCards, OMIM, PharmGKB and DrugBank databases to obtain GA related targets. The potential targets of Danggui Niantong Decoction in the treatment of GA were obtained by the intersection of mappings. The regulation network of Chinese medicine compound and protein-protein interaction network of Danggui Niantong Decoction were constructed by Cytoscape software, and the targets of Danggui Niantong Decoction in the treatment of GA were analyzed by GO and KEGG enrichment by David Database. Finally, molecular docking was performed by using Autodock software.Results:There are 198 active components that could treat GA in Danggui Niantong Decoction. The key active components are Quercetin and Kaempferol. There are 46 key targets, the core targets are NFE2L2, HMOX1, PPARA, PTGS2, IL1β, CXCL8. GO enrichment suggests that the key genes are primarily involved in many biological processes such as Inflammatory response regulation, response to oxidative stress, Fatty acid metabolism process, steroid metabolism, lipopolysaccharide response and reactive oxygen species metabolism. KEGG pathway indicates that Danggui Niantong Decoction mainly acted on IL-17 signal pathway, HIF-1 signal pathway, TNF signal pathway and AGE-RAGE signal pathway. Molecular docking shows that the active components of Danggui Niantong Decoction and action target of GA can combine toghether with high efficiency, and the structure is stable.Conclusion:Danggui Niantong Decoction has multi-component, multi pathway and multi-protein characteristics. Danggui Niantong Decoction can treat GA by regulating immune inflammatory reaction and oxidative stress reaction.

Effects of christina loosestrife and snowbellleaf tickclover herb on kidney calcium oxalate calculi related metabolites in rats / 国际外科学杂志

Objective:To compare the specific mechanism and effects between christina loosestrife and snowbellleaf tickclover herb on kidney calcium oxalate calculi in rats.Methods:A total of 54 SPF grade SD male rats were fed adaptically for 1 week to 180-200 g, the models of rats with kidney calcium oxalate calculi were established by intragastric administration with glycol, and divided into nine groups according to random number table method and controlled, which were healthy control group (group A), positive control group (model group, group B), low, medium and high doses of christina loosestrife groups (C1, C2, C3, 3 groups), low, medium and high doses of snowbellleaf tickclover herb groups (D1, D2, D3, 3 groups), therapeutic control group (potassium sodium hydrogen citrate group, group E), 6 rats in each group. After 4 weeks, samples were collected to determine the urine and serum biochemical indexes of each group, and Von Kossa staining was used to detect kidney calcium oxalate crystals. Calcium oxalate crystal deposition in kidney tissues of rats was observed under polarization microscope, and the difference of efficacy between the two drug effects was determined by the percentage of positive area in photos and the urine and serum biochemical indexes. The measurement data were expressed as mean ± standard deviation ( ± s), one-way analysis of variance was used for comparison between groups, and SNK- q test was used for comparison between two groups. Kruskal-Wallis test was used to compare crystal formation between groups. Results:Compared with the positive control group and christina loosestrife groups, high dose of snowbellleaf tickclover herb could significantly reduce serum creatinine level ( P<0.01), the mean serum creatinine of rats with christina loosestrife was (86.70±11.49) μmol/L, that of rats with snowbellleaf tickclover herb was (70.72±9.08) μmol/L, the difference was statistically significant ( P<0.01). High dose of christina loosestrife and snowbellleaf tickclover herb could significantly increase urinary magnesium and decrease serum urea levels, and there was no statistical significance between them ( P>0.05). Compared with the positive control group, high dose of christina loosestrife ( P<0.000 1) and snowbellleaf tickclover herb ( P<0.000 1) could both inhibit the formation of calcium oxalate crystals and protect the kidney of rats, and there was no statistical significance between the two effects ( P>0.05). The levels of urine pH value could not be increased, while the levels of urinary calcium urinary oxalic acid and 24 h urine volume, serum calcium, serum phosphorus, serum magnesium, blood uric acid and content of kidney oxalate could not be decreased significantly after using these two drugs. Conclusion:Snowbellleaf tickclover herb is better than christina loosestrife in preventing recurrence of kidney calcium oxalate calculi and protecting renal function.

Research on the mechanism of Xiaoluo Bolus in treating malignant lymphoma based on network pharmacology / 国际中医中药杂志

Objective:To analyze the pharmacological mechanism of Xiaoluo Bolus in treating Malignant Lymphoma based on network pharmacology so as to provide references for the R&D of new drugs and clinical use of classic formulation.Methods:This paper collected the main chemical components of Scrophulariaceae, Fritillaria, Oyster and their targets through TCMSP Database and selected active ingredients according to ADME. The main lymphoma target genes were acquired by GeneCards, OMIN, TTD, DURGBANK database. The main targets of Xiaoluo Bolus treating lymphoma were screened by using BisoGenet function in Cytoscape and PPI network of Xiaoluo Bolus compounds-Malignant Lymphoma target was constructed. Metascape data platform was used to analyze signal pathways of Xiaoluo Bolus and construct the network of Xiaoluo Bolus compounds-Malignant Lymphoma target-signal pathway.Results:The core effective ingredients of Xiaoluo Bolus which could treat Malignant Lymphoma were harpagoside, Zhebeiresinol, pelargonidin and the targets were PRS27A, TP53, PPP2CA, which mainly takes effect on NF-κB、HIF-1 pathways. The main function of them is to act on the rDNA chromatin silencing and megakaryocyte differentiation.The common deubiquitination function in these two pathways indicated the main therapeutic target of Xiaoluo Bolus treating malignant lymphoma.Conclusion:This study initially revealed the multi-component, multi-target, and multi-collateral mechanism of Xiaoluo Bolus, in the treatment of malignant lymphoma which provids the scientific base for the development and utilization of Xiaoluo Bolus in clinical use.

Research progress in the application of chemical space in the field of Traditional Chinese Medicine / 国际中医中药杂志

Combined with the related research progress of the application of chemical space in the field of Traditional Chinese Medicine (TCM), the common database resources and calculation tools of chemical space research are summarized and analyzed. The compatibility law of chemical space in TCM prescriptions, the screening of effective ingredients of TCMs, and TCM compounds are summarized. It was found that the current studies mainly focus on the efficacy and multi-target studies of TCMs and TCM compound, among which there are more studies on osteoarthritis and rheumatoid arthritis. The existing studies have clarified the efficacy and targets of TCMs or TCM compound for diseases, but there is still a lack of a database on the main components of all TCMs and the efficacy and main targets of TCM compound. Therefore, there needs a new database for the main efficacy molecules and targets of TCMs.

Study on molecular mechanism of Zuojin Pills for gastroesophageal reflux disease based on network pharmacology / 国际中医中药杂志

Objective:To analyze the possible mechanism of Zuojin Pills on gastroesophageal reflux disease based on network pharmacology. Methods:By searching for the active constituent and protein targets of Zuojin Pills in TCMSP database,the protein names were converted into gene names in Uniprot database. Cytoscape 3.7.1 was used to draw the active constituent-target-medicine network diagram of Zuojin Pills and analyze the topological parameters. Then find the target of gastroesophageal reflux disease through OMIM,GeneCards,DRUGBANK database, find the intersection target of medicine and disease, perform PPI network analysis on the intersection target in STRING 11.0, and use the Metascape database to enrich the intersection target for further analysis. Cytoscape 3.7.1 was used to draw a network diagram of the active constituent- target-pathway of the medicine and to conduct a topology parameter analysis. Results:The main active constituent of Zuojin Pills in the treatment of gastroesophageal reflux disease are quercetin, Evodiamine, R-tetrahydroberberine, 1-methyl-2-nonyl-4-quinolone, berberine, etc. Targets include PTGS2, NOS3, MAPK1, EGFR, TNF, IL6, ERBB2, VEGFA, EGF, IL1B, etc., and these processes are mainly completed through inflammatory response, cancer, cell proliferation and apoptosis, cell connection, etc. Conclusions:The treatment of gastroesophageal reflux disease with Zuojin Pills is a complex process with multiple constituent, multiple targets, and multiple pathways. It is hoped that it which could provide reference for the future research on its mechanism of action.

Mechanism of Huanglian-Jiedu Decoction against Helicobacter pylori infection based on network pharmacology / 国际中医中药杂志

Objective:To predict the main active constituent, targets and signaling pathways of Huanglian-Jiedu Decoction against Helicobacter pylori infection by using network pharmacology, and to explore its potential mechanism, so as to provide objective foundation for the following experimental research. Methods:Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) was used to screen the main active constituent and potential targets of Coptidis Rhizoma, Scutellaria baicalensis, Phellodendri Chinensis Cortex and Gardeniae Fructus in Huanglian-Jiedu Decoction. The targets related to Helicobacter pylori infection were screened by GeneCards suite database and human Mendelian genetic database (OMIM), and the intersection of Chinese herbs and disease targets was obtained. The Intersecting target were import into Cytoscape 3.7.2 to construct the network of active constituents and targets related to Helicobacter pylori infection. The protein protein interaction (PPI) network was constructed and analyzed by using string online analysis platform. Use R language to search Bioconductor platform online to enrich go function of targets. The enrichment of KEGG pathway was analyzed by David database. Results:total of 85 active constituent were screened from Huanglian-Jiedu Decoction, including quercetin, berberine, kaempferol, wogonin and baicalein. There are 112 corresponding targets, 1 960 disease-related targets and 71 common targets for herbal medicine and disease. Quercetin is the active constituent with the highest degree in the network diagram, and the target with the highest degree is cyclooxygenase-1 (PTGS1). In 69 nodes of PPI graph, the target proteins with the highest degree included CASP3, IL6, MAPK8, MYC, VEGFA and EGFR. A total of 89 items were obtained by GO functional enrichment analysis, and 12 signaling pathways with significant differences were screened by KEGG pathway enrichment analysis. Among them, pathways in cancer, ErbB Signal pathway, p53 signal pathway, apoptosis, and focal adhesion, which play a major role. Conclusions:Huanglian-Jiedu Decoction may treatm Helicobacter pylori with multi-component, multi-target and multi-pathway charateristics. At the same time, it may regulate the process of gastric cancer through anti-tumor mechanism, which could lay a foundation for the study of active components and anti-HP mechanism.

Mechanism of Xiaoyong Sanjie Formula treating non-puerperal mastitis based on network pharmacology / 国际中医中药杂志

Objective:Based on network pharmacology and molecular docking to explore the targets and mechanism of Xiaoyong Sanjie Formula treating Non-Puerperal Mastitis (NPM).Methods:By retrieving the active components and the corresponding target information of each component in Xiaoyong Sanjie Formula with Pharmacology Database and Analysis Platform of Chinese Medicine System (TCMSP), and NPM-related genes in database like GeneCard, OMIM, PharmGkb, TTD, and DrugBank, the data of the core targets of Xiaoyong Sanjie Formula and disease-related genes was compared to obtain intersecting genes, and the STRING database was used to analyze the protein interaction network and find the core genes. With the help of Cytoscape 3.8.0, the active ingredient-target-pathway regulation network diagram of Xiaoyong Sanjie Formula for the treatment of NPM was established. The R language pack was used to enrich the targets with GO function and KEGG pathway enrichment, and the potential targets and mechanism of Xiaoyong Sanjie Formula in the treatment of NPM were explored. Finally, molecular docking verification was carried out to analyze the effecacy of key components and potential core targets of Xiaoyong Sanjie Formula.Results:Network pharmacological analysis showed that there were 47 active component and 1 692 NPM-related potential targets in Xiaoyong Sanjie Formula, and 235 core targets of NPM in the treatment of Xiaoyong Sanjie Formula. The key components of Xiaoyong Sanjie Formula in the treatment of NPM include Quercetin, Naringenin, Kaempferol, Diosgenin, Luteolin, etc., with the core targets of intercellular adhesion molecule-1 (ICAM-1), vascular endothelial growth factor (VEGFA), tumor necrosis factor (TNF), interleukin-6 (IL-6), Epidermal growth factor receptor (EGFR), interleukin-1β (IL-1B), chemokine-8 (CXCL8), chemokine-2 (CCL2), etc. GO enrichment obtained 1 492 biological process entries. The KEGG pathway is enriched to obtain 105 pathways, including the TNF signaling pathway, the PI3K-Akt signaling pathway, the NF-kappa B signaling pathway, and the JAK-STAT signaling pathway, IL-17 signaling pathway, C-type lectin receptor signaling pathway, etc. The final molecular docking verified that the key active ingredients of Xiaoyong Sanjie Formula could bind with the potential core targets closely.Conclusion:Xiaoyong Sanjie Formula can treat NPM with multi-component, multi-target characteristics,which plays a role of treating NPM through signaling pathways such as immuno-inflammatory response, the metabolism of the medicine, cellular adaptive stress response, and vascular function regulation.

Mechanism of Banxia Houpo Decoction in the treatment of tension-type headache based on network pharmacology and molecular docking / 国际中医中药杂志

Objective:To explore the mechanism of the active compounds in Banxia Houpo Decoction treating tension type headache through network pharmacology and molecular docking.Methods:The potentially effective components and targets of Banxia Houpo Decoction were screened by TCMSP, and the action targets of tension type headache were obtained by GeneCards, PharmGKB, TTD, Drugbank and OMIM. The intersection target of "Banxia Houpo Decoction - tension type headache" was obtained by Perl software. The protein interaction network was uploaded to STRING database and topological analysis was carried out. With the help of Cytoscape 3.8.0 software, the visualization network of "Banxia Houpo Decoction - medicine ingredient-Target-tension type headache" was constructed, and the GO enrichment analysis and KEGG pathway enrichment analysis of the intersection targets were carried out by using R 4.1.0 language and related programs. The AutoDockTools-1.5.6 software was used to complete the molecular docking analysis.Results:There were 33 intersection targets in Banxia Houpo Decoction and tension type headache. Topological attribute analysis suggested that MAPK1, TP53, ESR1, PTGS2, MYC, CYP1A2, CYP3A4 and GSTP1 might be important potential targets of Banxia Houpo Decoction in the prevention and treatment of tension type headache. GO enrichment analysis showed 516 cell biological processes (BP), 62 cell components (CC) and 149 molecular functions (MF). KEGG pathway enrichment analysis showed that there were 94 related signal pathways, such as cGMP-PKG signaling pathway, Cholinergicsynapse, Serotonergic synapse and TNF signaling pathway.Conclusions:Banxia Houpo Decoction has multi-component, multi-target and multi-pathway characteristics in the prevention and treatment of tension-type headache. It mainly acts on 5-HT synaptic pathway, TNF signal pathway, cholinergic synaptic pathway, G protein coupled receptor pathway and other pathways through ESR1, TP53, PGTS2 and other multi target.

Mechanism of Hanchuan Zupa Granules in the treatment of Influenza A virus based on network pharmacology and molecular docking / 国际中医中药杂志

Objective:To explore the ingredients, targets, and mechanisms of Hanchuan Zupa Granules in the treatiment of Influenza A virus.Methods:By using Traditional Chinese Medicine Systems Pharmacology Database Analysis Platform (TCMSP), GeneCards, Online Mendelian Inheritance in Man (OMIM), Pharmacogenomics Knowledgebase (PharmGkb), Therapeutic target database (TTD) and DrugBank database to obtain relevant components and targets of Hanchuan Zupa Granules in the treatment of Influenza A virus; R software was used for the obtain of Hanchuan Zupa Granules -Influenza A virus intersection targets; Cytoscape software was applied for the construction of "Hanchuan Zupa Granules-component-target" network; Protein-protein interaction network (PPI) and topological analysis were constructed by STRING database and Cytoscape software. Intersection targets for gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were conducted by R software; Auto Dock Tools were used for molecular docking.Results:All together 111 potential active ingredients, with corresponding 131 targetswere identified from Hanchuan Zupa Granules in the treatment of Influenza A virus. Quercetin, apigenin, luteolin, kaempferol, wogonin, etc. are included as core ingredients. STAT3, MAPK1, MAPK3, AKT1, JUN, etc. are included as core targets. Intersection targets were mainly enriched in 178 signal pathways such as IL-17 signal pathway, influenza A signal pathway, TNF signal pathway, etc; Molecular docking showed that core component had a good affinity with the target.Conclusion:Hanchuan Zupa Granules could play the role of anti-Influenza A virus with multi-component-multi-target-multi-pathway,characteristics, and this syudy provide a basis for future experimental research on its mechanism.