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Poria sini decoction (PSD), a significant traditional Chinese herbal formula, is effective in liver cancer (LC) and chronic heart failure (CHF); however, little is known about its concurrent targeting mechanism. Methods. This study analyzed the potential molecular mechanism of PSD against the two distinct diseases using network pharmacology approaches, including multidatabase search, pharmacokinetic screening, network construction analysis, Gene Ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and molecular docking to elaborate the active components, signaling pathways, and potential mechanisms of PSD in the treatment of both LC and CHF. Results. A total of 155 active components and 193 potential targets in PSD were identified. Bioinformatics analysis revealed that quercetin, isorhamnetin, and naringenin, etc. may be potential candidate agents. TNF, AKT1, and IL6, etc. could become potential therapeutic targets. TNF-α, NF-κB, PI3K-AKT, and TRP signaling pathways might play an important role in PSD against LC and CHF. Molecular docking results showed that most screened active compounds could embed itself into target proteins with a high binding affinity, and the hydrogen bonds number ≥3 indicated a more stable conformation of the compounds and target proteins. Overall, quercetin and isorhamnetin were the main active components, and TNF and AKT1 were the primary targets for PSD treatment of LC and CHF. Conclusions. This study illustrated that quercetin contained in PSD played an important role in the treatment of LC and CHF by acting on the key gene of TP53 and downregulating the PI3K-AKT signaling pathway. [ABSTRACT FROM AUTHOR]

Objective. This study aimed to explore the mechanisms of Baishi tablets (BSTs) in the treatment of vitiligo through network pharmacology-based identification and experimental validation. Methods. In brief, the compounds and related targets of BST were extracted from the TCMSP database, and disease information was obtained from the OMIM, GeneCards, PharmGkb, TTD, and DrugBank databases. A Venn diagram was generated to visualize the common targets of BST and vitiligo. GO and KEGG analyses were performed to explore the potential biological processes and signaling pathways. The PPI network and core gene subnetwork were constructed using STRING and Cytoscape software. In addition, the measurement of apoptosis in PIG1 cells and intracellular reactive oxygen species were measured using quercetin (QU), luteolin (LU), and kaempferol (KA) to protect melanocytes from oxidative stress. Results. A total of 55 compounds with 236 targets and 1205 vitiligo-related genes were obtained from the TCMSP database. GO and KEGG analyses were performed to explore the potential biological processes and signaling pathways, revealing that BST may cure vitiligo by influencing the biological processes of cellular oxidative stress and related signaling pathways. A critical subnetwork was obtained with 13 core genes by analyzing the PPI network, which includes HMOX1, CXCL8, CCL2, IL6, MAPK8, CASP3, PTGS2, AKT1, IL1B, MYC, TP53, IFNG, and IL2. Furthermore, a molecular docking analysis was conducted to simulate the combination of compounds and gene proteins, reflecting that QU, LU, and KA can strongly bind the core genes. Through a series of experimental validations, we found that QU, LU, and KA could attenuate H2O2-induced apoptosis in melanocytes. Further evidence revealed that QU, LU, and KA could enhance the scavenging of intracellular reactive oxygen species (ROS). Conclusion. Based on the results of network pharmacology analysis and experimental verification, QA, LU, and KA can be utilized to protect PIG1 cells by inhibiting oxidative stress and reducing the intracellular level of ROS. This may explain the underlying mechanism of BST therapy and provide a novel strategy for the treatment of vitiligo. [ABSTRACT FROM AUTHOR]

Myasthenia gravis (MG) is a rare and refractory autoimmune disease, and Qi Shen Di Huang (QSDH) drug formulary is an in-hospital herbal decoction with proven clinical efficacy in treating MG. Currently, most of the research on the QSDH drug formulary has concentrated on its clinical efficacy, and there is a lack of systematic study on the material basis. The active compounds and their mechanism of action have not been entirely determined. Therefore, this study sought to identify the active compounds in the QSDH drug formulary and analyze the key targets and potential mechanisms. We used ultra-performance liquid chromatography Q Exactive-mass spectrometry (UHPLC-QE-MS) and Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) database to identify and screen 85 active ingredients corresponding to 59 potential targets (17 herbs) associated with myasthenia gravis, and further identified AKT1 as the primary core target and the PI3K/AKT signaling pathway as the most substantial enriched pathway. Molecular docking and UPLC-MS analysis identified quercetin, luteolin, wogonin, kaempferol, laccasein, and epigallocatechin gallate are the core compounds of the QSDH drug formulary. In vivo rat studies showed that the QSDH drug formulary reduced Lennon's clinical score and decreased acetylcholine receptor antibody levels in peripheral blood rats with experimental autoimmune myasthenia gravis. In addition, the QSDH drug formulary downregulated P-PI3K/PI3K and P-Akt/Akt protein expression. Collectively, these findings describe the role and potential mechanism of the QSDH drug formulary in the treatment of MG, which exerts potential value by acting on AKT targets and regulating the PI3K/AKT signaling pathway and providing a theoretical reference for QSDH drug formulary application in the clinical treatment of MG. [ABSTRACT FROM AUTHOR]

Objective. The purpose of this study was to investigate the mechanisms of action of Tong Xie Yao Fang (TXYF) against ulcerative colitis (UC) by employing a network pharmacology approach. Methods. The network pharmacology approach, including screening of the active ingredients and targets, construction of the active ingredient-drug target network, the active ingredient-diseasetarget network, the protein–protein interaction (PPI) network, enrichment analyses, molecular docking, and targets validation, was used to explore the mechanisms of TXYF against UC. Results. 34 active ingredients and 129 and 772 targets of TXYF and UC, respectively, were identified. The intersection of the active ingredient-drug target network, the active ingredient-disease target network, and the PPI network suggested that kaempferol, beta-sitosterol, wogonin, and naringenin were the core ingredients and prostaglandin-endoperoxide synthase 2 (PTGS2) was the core target. Enrichment analyses showed that regulation of exogenous protein binding and other functions were of great significance. Nuclear factor-kappa B (NF-κB) signaling pathway, interleukin-17 (IL-17) signaling pathway, and tumor necrosis factor (TNF) signaling pathway were important pathways. Results of molecular docking indicated that the core ingredients and the target molecule had strong binding affinities. We have validated the high levels of expression of PTGS2 in UC by analyzing three additional datasets from the Gene Expression Omnibus (GEO) database. Conclusions. There are multiple ingredients, targets, and pathways involved in TXYF's effectiveness against UC, and these findings will promote further research and clinical applications. [ABSTRACT FROM AUTHOR]

The Shugan Hewei recipe (SHR) is a well-recognized traditional Chinese medicine (TCM) prescription that has been shown to significantly improve chest pain, acid regurgitation, and the mood of GERD. Nonetheless, the underlying mechanisms remain unclear. In this study, the active compounds and targets of SHR were predicted using network pharmacology. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were utilized to explore the therapeutic mechanism of SHR. Combined with the drug target obtained from network pharmacology, the therapeutic effect and mechanism of SHR were observed. SHR's main active compounds included quercetin, kaempferol, and luteolin. The core targets of SHR and GERD were TGF-β1, IL-1β, IL-4, CXCL10, MAPK1, MAPK3, CXCL8, IL-10, IL-2, and FOS, involving virus infection, inflammatory response, and body immunity. The core targets of SHR during the treatment of mental disorders were GABRA1, GABRA2, GABRA3, GABRA5, and GABRA6, involving synaptic transmission and transmembrane movement. Animal experiments revealed that SHR could repair the lower esophageal mucosa, mediate inflammatory factors, and GABA receptors and improve the behavior of rats. Overall, our results substantiate that SHR has huge prospects for widespread application in treating GERD subjects with anxiety and depression. [ABSTRACT FROM AUTHOR]

Objective. To assess the efficacy of mecobalamin tablets combined with troxerutin in the treatment of nonsmall cell lung cancer (NSCLC) chemotherapy-induced peripheral neuropathy (CIPN). Methods. From January 2020 to December 2021, 120 NSCLC patients with CIPN treated in our institution meeting the inclusion criteria were enrolled and assigned to receive mecobalamin tablets treatment in the control group, or assigned to receive mecobalamin tablets combined with troxerutin treatment in the research group, with 60 patients in each group. All patients were evaluated for clinical efficacy, neuropathic score, patient-reported CIPN symptoms, neuropathic pain grade, and quality of life after 3 weeks of treatment. Results. The clinical treatment effective rate of the patients in the research group was significantly higher than that of the patients in the control group (81.7% vs. 58.3%, P < 0.05). Compared with before treatment, neuropathic score, numbness and tingling score, hot/coldness in hands/feet score, and peripheral neurotoxicity grade in all patients decreased significantly after treatment (P < 0.05). And these reductions were more considerable in the research group compared to the control group (P < 0.05). In addition, the quality of life scores (EORTC QLQ-C30) increased significantly in all patients after treatment, and this rise was more considerable in the research group compared to the control group (P < 0.05). Conclusion. Mecobalamin tablets combined with troxerutin in the treatment of NSCLC patients with CIPN is effective and safe, and can significantly improve the symptoms and quality of life of NSCLC patients with CIPN. [ABSTRACT FROM AUTHOR]

Objective. The lung is the second most common site of colorectal cancer (CRC) metastasis. This study aims to investigate the therapeutic effects and potential action mechanisms of Yifei Jianpi Tongfu formula (YJTF) in CRC lung metastasis in a comprehensive and systematic way by network analysis, molecular docking, and experimental verification. Methods. The main ingredients in YJTF were screened from the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform (TCMSP) and Traditional Chinese Medicine Integrated Database (TCMID), and the disease-related targets from the Online Mendelian Inheritance in Man (OMIM) and GeneCards and the compound-related targets from SwissTargetPrediction were collected. Then, Metascape was used for pathway annotation and enrichment analysis, and meanwhile, a protein-protein interaction (PPI) network was constructed. Molecular docking was carried out to investigate interactions between the active compounds and the potential targets. The in vivo effect of YJTF on CRC lung metastasis was observed in a tail vein injection mouse model. Results. A total of 243 active compounds and 81 disease-related targets of YJTF were selected for analysis. The results of multiple network analysis showed that the core targets of YJTF were enriched onto various cancer-related pathways, especially focal adhesion and adherens junction. The results of molecular docking demonstrated that all core compounds (quercetin, kaempferol, luteolin, apigenin, and isorhamnetin) were capable of binding with AKT1, EGFR, SRC, ESR1, and PTGS2. Experimental validation in vivo demonstrated that YJTF combined with oxaliplatin could significantly reduce the number of lung metastases and improve the quality of life in mice. Further research suggested that YJTF inhibited CRC lung metastasis probably by modulating epithelial-to-mesenchymal transition (EMT). Conclusions. According to the analysis, YJTF can be considered as an effective adjuvant therapy for CRC lung metastasis. [ABSTRACT FROM AUTHOR]

Background. JinGuanLan (JGL) formula is a traditional Chinese medicine (TCM) developed by the Department of Pharmacology at the First Hospital of Lanzhou University. The network pharmacology approach was applied to determine the potential active compounds, therapeutic targets, and main pathways of the JGL formula to evaluate its application value in acne vulgaris. Methods. Data on the active compounds and their related targets were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Acne vulgaris-related targets were searched from the Online Mendelian Inheritance in Man (OMIM) database, GeneCards Database, Comparative Toxicogenomics Database (CTD), Therapeutic Target Database (TTD), and DisGeNET Database. Targets intersecting between JGL- and acne vulgaris-related targets were chosen as potential therapeutic targets. The protein-protein interaction (PPI) network of potential therapeutic targets was visualized using Cytoscape software based on the PPI data collected from the STRING database. Three topological features, namely, "Degree," "MCC," and "EPC" of each node in the PPI network were calculated using the cytoHubba plugin of Cytoscape to excavate the core targets. R program was used for the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of the potential therapeutic targets. Finally, the compound–target–pathway network was constructed. Result. Among the 148 active compounds that were identified, quercetin and kaempferol showed the highest degree of target interaction and thus may play essential roles in the pharmacological effect of the JGL formula for acne treatment. Among the 97 potential therapeutic targets that were screened out, the 6 core targets were TNF, JUN, IL6, STAT3, MAPK1, and MAPK3. A total of 2260 terms of GO enrichment analysis were obtained, including 2090 for biological processes (BP), 37 for cellular components (CC), and 133 for molecular function (MF). A total of 156 enriched KEGG pathways were identified, including TNF, IL-17, Th17 cell differentiation, MAPK, PI3K-Akt, T cell receptor, and Toll-like receptor signalling pathways. Conclusion. This work showed that the JGL formula might reverse the pathological changes associated with acne vulgaris through its antiinflammatory effect and regulate the excessive lipogenesis in sebaceous glands via different signalling pathways. This new drug has application value and is worthy of further research and development. [ABSTRACT FROM AUTHOR]

Background. Shenqi pill (SQP), a traditional Chinese prescription, has proven to be effective in treating nonalcoholic fatty liver disease (NAFLD). However, its bioactive ingredients and underlying mechanisms remain elusive. Aim. We aimed to predict the active compounds, potential targets, and molecular mechanisms of SQP anti-NAFLD by applying network pharmacology and molecular docking methods. Methods. Active ingredients and related targets of SQP were obtained from the TCMSP database. Potential targets of NAFLD were acquired from OMIM and GeneCards databases. The STRING database and Cytoscape software analyzed the protein-protein interaction (PPI) network and core targets of overlapping genes between SQP and NAFLD. GO enrichment analysis and KEGG enrichment analysis were performed in the DAVID database. Finally, molecular docking was employed to find possible binding conformations of macromolecular targets. Results. 15 anti-NAFLD bioactive ingredients and 99 anti-NAFLD potential targets of SQP were determined using Network pharmacology. Quercetin, kaempferol, stigmasterol, diosgenin, and tetrahydroalstonine were the major active ingredients and AKT1, TNF, MAPK8, IL-6, and VEGFA were the key target proteins against NAFLD. The KEGG analysis suggested that the main pathways included PI3K/Akt signaling pathway, HIF-1 signaling pathway, MAPK signaling pathway, and TNF signaling pathway. Molecular docking predicted that quercetin, kaempferol, stigmasterol, diosgenin, and tetrahydroalstonine could bind with AKT1, TNF, and MAPK8. Conclusion. This study successfully predicts the active compounds, potential targets, and signaling pathways of SQP against NAFLD. Moreover, this study contributed to the application and development of SQP. [ABSTRACT FROM AUTHOR]

Kui Jie Kang (KJK)—a traditional Chinese medicine—has demonstrated clinical therapeutic efficacy against ulcerative colitis (UC). However, the active compounds and their underlying mechanisms have not yet been fully characterized. Therefore, the current study sought to identify the volatile compounds in KJK responsible for eliciting the therapeutic effect against UC, while also analyzing key targets and potential mechanisms. To this end, systematic network pharmacology analysis was employed to obtain UC targets by using GeneCards, DisGeNET, OMIM, among others. A total of 145 candidate ingredients, 412 potential targets of KJK (12 herbs), and 1605 UC targets were identified. Of these KJK and UC targets, 205 intersected and further identified AKT1, JUN, MAPK, ESR, and TNF as the core targets and the PI3K/AKT signaling pathway as the top enriched pathway. Moreover, molecular docking and ultra-performance liquid chromatography Q Exactive-mass spectrometry analysis identified quercetin, kaempferol, luteolin, wogonin, and nobiletin as the core effective compounds of KJK. In vivo murine studies revealed that KJK exposure increases the body weight and colon length, while reducing colonic epithelial injury, and the expression of inflammatory factors in colitis tissues such as TNF-α, IL-6, and IL-1β. Furthermore, KJK treatment downregulates the expression of pi3k and akt genes, as well as p-PI3K/PI3K and p-AKT/AKT proteins. Collectively, these findings describe the therapeutic effects and mechanisms of KJK in UC and highlight KJK as a potentially valuable therapeutic option for UC via modulation of the PI3K/AKT signaling pathway, thus providing a theoretical reference for the broader application of KJK in the clinical management of UC. [ABSTRACT FROM AUTHOR]

Background. Yiqi Yangjing prescription (YQYJ) is a traditional Chinese medicine prescription used for treating lung cancer. It has a significant effect on enhancing efficacy, reducing toxic symptoms, and improving patients' physical well-being. The effective inhibitory effect on nonsmall-cell lung cancer (NSCLC) has been demonstrated in vitro and in vivo. However, the mechanism of action and the material basis still remain unclear. Methods. In this study, we explored this mechanism using network pharmacology, after which we explored the pharmacodynamics and the action mechanism of YQYJ using cell viability evaluation, plate clone formation assay, flow cytometry, real-time quantitative PCR, and Western blot. Results. The enrichment results showed that there were 50 active components and 68 core targets related to YQYJ inhibiting NSCLC, including quercetin, luteolin, gamatin, kaempferol, heat shock protein HSP 90-alpha (HSP90AA1), cyclin-dependent kinase 2 (CDK2), epidermal growth factor receptor (EGFR), signal transducer and activator of transcription 3 (STAT3), and others. Among them, quercetin and kaempferol revealed the best binding effect with core targets. Most importantly, YQYJ promoted A549 cells from the quiescent phase into the proliferative phase to enhance the sensitivity of A549 cells to YQYJ and inhibited the proliferation of A549 cells significantly (P < 0.05). The A549 cells were blocked in both S and G2/M phases while the apoptosis ratio was increased. The proliferation score of A549 cells treated with YQYJ was significantly reduced compared to A549 cells in the proliferative phase (P < 0.05). This regulatory effect was related to the expression regulation of HSP90AA1, CDK2, STAT3, and phosphor-STAT3 (p-STAT3) by YQYJ, kaempferol, and quercetin. Conclusion. Our results suggested that the inhibition of NSCLC via YQYJ had multicomponent and multitarget characteristics. Its core mechanism is related to the regulation of the cell cycle, proliferation, and apoptosis of NSCLC. This study provides a direction and scientific basis for exploring the future mechanism of YQYJ for the treatment of NSCLC. [ABSTRACT FROM AUTHOR]

Background. Duhuo Jisheng Decoction (DHJSD) is an ancient compound widely used in the treatment of ankylosing spondylitis (AS). However, its efficacy is controversial, and its mechanism of action is not clear enough. Using meta-analysis and network pharmacology, our study evaluated the clinical efficacy of DHJSD in the treatment of AS and explored its mechanisms of action. Methods. We searched medical databases, including Embase, PubMed, the China National Knowledge Infrastructure databases, Wanfang, and the Chinese Scientific Journal Database, to identify studies that met the inclusion criteria. RevMan 5.3 software was used for the meta-analysis. The compounds and the potential protein targets of DHJSD were obtained from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database and analysis platform. AS was treated as a search query in the NCBI, PharmGKB, TTD, DrugBank, and OMIM databases to obtain disease-related genes. The overlapping targets of DHJSD and AS were identified, and then Gene Ontology functional enrichment and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed. Cytoscape was employed to construct a drug-compound-target network and a protein-protein interaction (PPI) network. CytoHubba was utilized to select the hub genes. Results. A total of 10 studies involving 860 participants were included in the meta-analysis. Compared with the control, DHJSD treatment significantly improved clinical symptoms; reduced the erythrocyte sedimentation rate (ESR), the C-reactive protein (CPR), and interleukin 6 (IL-6) levels; increased the degree of motion of the chest; reduced the visual analog scale (VAS) pain score; reduced Schober's test values; reduced the finger-to-floor distance; reduced the duration of morning stiffness. However, the differences were not statistically significant in the Bath Ankylosing Spondylitis Functional Index scores, the Bath Ankylosing Spondylitis Disease Activity Index scores, the bone Gla-containing protein (BGP) levels, or the bone alkaline phosphatase (BALP) levels. In terms of adverse events, DHJSD treatment of AS reduced the incidence of gastrointestinal events, the incidence of skin events, and the incidence of abnormal liver function; however, there was no statistically significant reduction in the incidence of adverse renal function events. Subgroup analysis showed that in the treatment of AS, the clinical effect of DHJSD for AS was better than that of the controls for both treatment durations, ≤2 months and >2 months. A total of 178 active compounds and 47 related potential targets were identified for DHJSD in the treatment of AS, including four hub genes (CXCL8, PTGS2, VEGFA, and STAT3). The core active ingredients of DHJSD in the treatment of AS were mainly quercetin, kaempferol, licochalcone A, and isorhamnetin. DHJSD treatment of AS-related pathways mainly involved the IL-17 signaling pathway, the TNF signaling pathway, and the rheumatoid arthritis signaling pathway. Conclusion. The above results suggest that DHJSD acts on AS through multiple targets, components, and pathways with significant clinical efficacy. Future studies may further explore the active components of DHJSD. [ABSTRACT FROM AUTHOR]

Dietary nutraceutical compounds have been evidenced as backbone for bone health in recent years. It is reported that medicine food homology (MFH) plants have multiple nutraceutical compounds. Based on our literature research, 20 MFH plants caught our attention because they contain three popular antiosteoporosis compounds simultaneously: quercetin, rutin, and kaempferol. According to traditional Chinese medicine (TCM), their characteristics including natures, flavors, attributive to meridian tropism, and efficacies were listed. The relationships between TCM efficacies, such as "heat clearing," "tonic," and "the interior warming," and antiosteoporosis pharmacological actions such as antioxidant and immune regulation were discussed. The in vivo antiosteoporosis effects of the 20 MFH plants were summarized. The in vitro antiosteoporosis activities and related mechanisms of the 20 plants and quercetin, rutin, kaempferol were detailed. The TGF-β-Smad signaling, fibroblast growth factor, and Wnt/β-catenin signaling on bone formation and the RANKL signaling, NF-κB signaling, and macrophage-colony-stimulating factor on bone resorption were identified. From food point, these 20 MFH plants could be classified as condiment, vegetable, fruit, tea and related products, beverage, etc. Based on the above discussion, these 20 MFH plants could be used as daily food supplements for the prevention and treatment against osteoporosis. [ABSTRACT FROM AUTHOR]

Objective. This study aimed to ascertain the immuno-inflammatory molecular targets of Xinfeng capsules (XFC) in the treatment of ankylosing spondylitis (AS) based on data mining, network pharmacology, and molecular docking. Methods. The efficacy of XFC in the treatment of AS was assessed by clinical data mining. Network pharmacology was utilized to establish a network of the targets for XFC active ingredients in the treatment of AS. The binding mode and affinity of XFC active ingredients to the key targets for AS were predicted using molecular docking. Results. XFC significantly diminished immuno-inflammatory indicators of AS. In total, 208 targets of XFC were obtained from the TCMSP database and 629 disease targets of AS were screened from the GeneCards database, which were intersected to yield 57 targets of XFC in the treatment of AS. Protein-protein interaction, gene ontology, and Kyoto genome encyclopedia analyses showed that XFC might activate TNF and NF-κB signaling pathways. Quercetin, kaempferol, triptolide, and formononetin had free binding energies < -9 kcal/mol to inflammatory targets (TNF and PTGS2) in the molecular docking analysis of XFC-active ingredients, indicating that TNF and PTGS2 might be the targets of the action of XFC. Conclusions. Collectively, XFC had a significant therapeutic effect on AS. Specifically, the active ingredients of XFC, including quercetin, kaempferol, triptolide, and formononetin, inhibited the inflammatory response in AS by downregulating TNF and PTGS2 in the TNF and NF-κB signaling pathways. [ABSTRACT FROM AUTHOR]

Background. Houttuynia cordata Thunb. is a traditional Chinese herb widely used mainly because of the pharmacological effects related to heat clearance and detoxification. Emerging clinical evidence indicates that the efficacy of Houttuynia cordata Thunb. on RILI is upstanding. Nevertheless, its underlying therapeutic mechanism remains unclear and warrants further elucidation. Methods. The major active components and corresponding targets of Houttuynia cordata Thunb. were retrieved from the traditional Chinese medicine system pharmacology database (TCMSP) and literature review. The related targets of RILI were retrieved from the GeneCards database. Common targets among the active compounds and diseases were identified through Venn diagram analysis. Cytoscape was employed to construct and visualize the network relationship among the drug, active compounds, targets, and disease. The protein interaction network (PPI) was constructed by STRING. The reliability (the binding affinity) of the core targets and active compounds was verified by molecular docking. Results. A search of the TCMSP database and related literature revealed 12 active compounds of Houttuynia cordata Thunb. against RILI. The core active compounds included quercetin, kaempferol, hyperoside, and rutin. Hub nodes including TP53, VEGFA, JUN, TNF, and IL-6 were identified in the PPI network. The GO categories were classified into three functional categories: 112 biological processes, 9 molecular functions, and 32 cellular components of the active compounds of Houttuynia cordata Thunb. The KEGG pathway enrichment analysis demonstrated the enrichment of target genes in several key cancer-related signaling pathways, including the cancer pathways, TNF signaling pathway, PI3K-Akt signaling pathway, and HIF-1 signaling pathway. Molecular docking analysis validated the effective binding capacity of the main active compounds with the core targets. Conclusion. The main active components of Houttuynia cordata Thunb. have a potential pharmacological effect against RILI via the cancer pathways, TNF signaling pathway, and PI3K-Akt signaling pathway. [ABSTRACT FROM AUTHOR]

Heart failure (HF) is a serious manifestation or advanced stage of various cardiovascular diseases, and its mortality and rehospitalization rate are still on the rise in China. Based on the network pharmacology method, 59 components of Zhen Wu decoction (ZWD) and 83 target genes related to HF were obtained. Through the PPI network, four potential therapeutic targets were identified: AKT1, IL6, JUN, and MAPK8. The beneficial components of ZWD might intervene HF through the AGE-RAGE signalling pathway in the diabetes component, fluid shear stress and atherosclerosis, the TNF signalling pathway, TB, and Kaposi sarcoma related herpesvirus infection, according to a KEGG enrichment study. The protein interaction network of candidate targets was constructed by the STRING database, and the protein interaction network was clustered by MEODE software. GO and KEGG enrichment analyses were performed on the core modules obtained by clustering. Finally, AutoDock Vina software was used for molecular docking verification of key targets and active ingredients. The result was that 75 active ingredients and 109 genes were screened as potential active ingredients and potential targets of Shengjie Tongyu decoction for CHF treatment. The main active components were quercetin, luteolin, kaempferol, dehydrated icariin, isorhamnetin, formononetin, and other flavonoids. Il-6, MAPK1, MAPK8, AKT1, VEGFA, and JUN were selected as the core targets. Molecular docking showed that the key components were well connected with the target. GO enrichment analysis showed that Shengjie Tongyu decoction could play a role through multiple biological pathways including angiogenesis, regulation of endothelial cell proliferation, binding of cytokine receptors, negative regulation of apoptotic signalling pathways, regulation of nitric oxide synthase activity, and reactive oxygen metabolism. Key pathways mainly focus on the toll-like receptor signalling pathway, nod-like receptor signalling pathway, MAPK signalling pathway, mTOR signalling pathway, JAK-STAT signalling pathway, VEGF signalling pathway, and other pathways. Through molecular docking technology, it was found that a variety of effective components in ZWD, such as kaempferol. Molecular docking technology has preliminatively verified the network pharmacology and laid a foundation for the follow-up pharmacological research. [ABSTRACT FROM AUTHOR]

The traditional medicine Dingqing Tablet produces effective efficacy in treating acute myeloid leukemia, but its specific mechanism remains to be investigated. Dingqing Tablet consists of Codonopsis, Indigo Naturalis, Cortex Moutan, Radix Notoginseng, Citrus Reticulata, and Eolite. The active components of Dingqing Tablets were screened by the TCMSP database. Meanwhile, the SwissTargetPrediction database was utilized to predict the corresponding targets. Relevant disease targets of acute myeloid leukemia were obtained from GeneCards. The obtained targets of Dingqing Tablets and genes of acute myeloid leukemia were used, and the overlapped genes were presented in the Venn diagram. A drug-component-target network was constructed via Cytoscape 3.6.0 software. Molecular docking methodology was also used with AutoDock Vina 1.1.2. Furthermore, the effects of kaempferol on the proliferation and apoptosis of HL-60 cells were identified using 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide (MTT), 5-Ethynyl-2′-deoxyuridine (EDU), flow cytometry, and TdT-mediated dUTP nick-end labeling (TUNEL) assays. The combination of kaempferol and AKT1 was verified using an immunoprecipitation (IP) experiment and the effects of Kaempferol on HL-60 cell apoptosis by western blot (WB) and qPCR. The key component kaempferol and the core target gene AKT1 were sorted out using a drug-component target network diagram. Molecular docking results revealed that the binding energy between kaempferol and AKT1 was lower than -5 kcal/mol. MTT and EDU assays indicated that kaempferol markedly inhibited the proliferation of HL-60 cells. Flow cytometry and TUNEL assays suggested that kaempferol substantially promoted HL-60 cell apoptosis. IP assay results testified that kaempferol could bind to AKT1, thereby reducing the level of P-AKT and promoting HL-60 cell apoptosis. The monomer kaempferol of Dingqing Tablet could promote apoptosis of HL-60 cells, and the mechanism might correlate with the combination of kaempferol and AKT1, reducing the level of P-AKT and promoting the expression of the apoptotic signaling pathway. [ABSTRACT FROM AUTHOR]

Kaempferol (KP), as a natural anti-inflammatory compound, has been reported to have curative effects on alleviating senile osteoporosis (SOP), which is an inflammation-related musculoskeletal disease, but the molecular mechanisms remain unclear due to scanty relevant studies. We predicted the targets of KP and SOP, and the common targets of them were subsequently used to carry out PPI analysis. Moreover, we adopted GO and KEGG enrichment analysis and molecular docking to explore potential mechanisms of KP against SOP. There were totally 152 KP-related targets and 978 SOP-related targets, and their overlapped targets comprised 68 intersection targets. GO enrichment analysis showed 1529 biological processes (p < 0.05), which involved regulation of inflammatory response, oxidative stress, regulation of bone resorption and remodeling, osteoblast and osteoclast differentiation, etc. Moreover, KEGG analysis revealed 146 items including 44 signaling pathways (p < 0.05), which were closely linked to TNF, IL-17, NF-kappa B, PI3K-Akt, MAPK, estrogen, p53, prolactin, VEGF, and HIF-1 signaling pathways. By means of molecular docking, we found that kaempferol is bound with the key targets' active pockets through some connections such as hydrogen bond, pi-alkyl, pi-sigma, pi-pi Stacked, pi-pi T-shaped, and van der Waals, illustrating that kaempferol has close combination with the key targets. Collectively, various targets and pathways involve in the process of kaempferol treatment against SOP through regulating inflammatory response, oxidative stress, bone homeostasis, etc. Moreover, our study first reported that kaempferol may regulate core targets' expression with involvement of inflammatory response, oxidative stress, and bone homeostasis, thus treating SOP. [ABSTRACT FROM AUTHOR]

Background. Astragalus membranaceus (AM, family: Leguminosae) exerts significant therapeutic effect on gastric ulcer (GU); however, there are scarce studies on its molecular mechanism against GU. This study aims to explore the key ingredients, key targets, and potential mechanisms of AM in the treatment of GU by utilizing network pharmacology and molecular docking. Methods. Several public databases were used to predict the targets of AM and GU, respectively, and the drug and disease targets were intersected to obtain the common targets. Next, the key ingredients and key targets were identified by constructing ingredient-target network and protein-protein-interaction (PPI) network. Gene Ontology biological processes (GOBP) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were carried out on the common targets in order to ascertain the biological processes and signaling pathways involved. Finally, molecular docking was conducted to verify the binding affinity between the key ingredients and key targets. Results. A total of 552 predicted targets were obtained from 23 screened active ingredients, of which 203 targets were the common targets with GU. Quercetin, kaempferol, and isorhamnetin were identified as the key ingredients by constructing ingredient-target network, and TP53, AKT1, VEGFA, IL6, TNF, CASP3, and EGFR were selected as the key targets by constructing PPI network. GOBP and KEGG pathway enrichment analysis suggested that the therapeutic effect of AM on GU involved multiple biological processes and signaling pathways related to inflammation, oxidative stress, apoptosis, cell proliferation, and angiogenesis. Molecular docking validation demonstrated that all key ingredients had good binding affinity with the key targets. Conclusion. This study revealed the key ingredients, key targets, and potential mechanisms of AM against GU, and these data may provide some crucial references for subsequent research and development of drugs for treating GU. [ABSTRACT FROM AUTHOR]

Objective. Tinglizi has been extensively used to treat chronic heart failure (CHF) in modern times, but the material basis and pharmacological mechanisms are still unclear. To explore the material basis and corresponding potential targets and to elucidate the mechanism of Tinglizi, network pharmacology and molecular docking methods were utilized. Methods. The main chemical compounds and potential targets of Tinglizi were collected from the pharmacological database analysis platform (TCMSP). The corresponding genes of related action targets were queried through gene cards and UniProt database. The corresponding genes of CHF-related targets were searched through Disgenet database, and the intersection targets were obtained by drawing Venn map with the target genes related to pharmacodynamic components. Then, drug targets and disease targets were intersected and put into STRING database to establish a protein interaction network. The "active ingredient-CHF target" network was constructed with Cytoscape 3.8.2. Finally, Gene Ontology (GO) Enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment of intersection targets were analyzed using metascape. With the aid of SYBYL software, the key active ingredients and core targets were docked at molecular level, and the results were visualized by PyMOL software. Molecular docking was carried out to investigate interactions between active compounds and potential targets. Results. A total of 12 active components in Tinglizi were chosen from the TCMSP database, and 193 corresponding targets were predicted. Twenty-nine potential targets of Tinglizi on CHF were obtained, of which nine were the core targets of this study. Twenty GO items were obtained by GO function enrichment analysis (P < 0.05), and 10 signal pathways were screened by KEGG pathway enrichment analysis (P < 0.05), which is closely related to the treatment of CHF by Tinglizi. The constructed drug compound composition action target disease network shows that quercetin, kaempferol, and other active compounds play a key role in the whole network. The results of molecular docking showed that all the key active ingredients, such as quercetin and isorhamnetin, were able to successfully dock with ADRB2 and HMOX1 with a total score above 5.0, suggesting that these key components have a strong binding force with the targets. Conclusion. Through network pharmacology and molecular docking technology, we found that the main components of Tinglizi in the treatment of CHF are quercetin, kaempferol, β-sitosterol, isorhamnetin, and so on. The action targets are beta 2-adrenergic receptor (ADRB2), heme oxygenase 1 (HMOX1), and so on. The main pathways are advanced glycation end products/receptor for advanced glycation end products (AGE-RAGE) signaling pathway in diabetic complications, hypoxia-inducible factor (HIF-1) signaling pathway, estrogen signaling pathway, and so on. They play an integrated role in the treatment of CHF. [ABSTRACT FROM AUTHOR]

Objective. The purpose of this study was to explore the molecular mechanism of Danggui Buxue Decoction (DBD) intervening premature ovarian failure (POF). Methods. The active compounds-targets network, active compounds-POF-targets network, and protein-protein interaction (PPI) network were constructed by a network pharmacology approach: Gene Ontology (GO) function and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway analysis by DAVID 6.8 database. The molecular docking method was used to verify the interaction between core components of DBD and targets. Then, High-Performance Liquid Chromatography (HPLC) analysis was used to determine whether the DBD contained two key components including quercetin and kaempferol. Finally, the estrous cycle, organ index, ELISA, and western blot were used to verify that mechanism of DBD improved POF induced by cyclophosphamide (CTX) in rats. Results. Based on the network database including TCMSP, Swiss Target Prediction, DisGeNET, DrugBank, OMIM, and Malacard, we built the active compounds-targets network and active compounds-POF-targets network. We found that 2 core compounds (quercetin and kaempferol) and 5 critical targets (TP53, IL6, ESR1, AKT1, and AR) play an important role in the treatment of POF with DBD. The GO and KEGG enrichment analysis showed that the common targets involved a variety of signaling pathways, including the reactive oxygen species metabolic process, release of Cytochrome C from mitochondria and apoptotic signaling pathway, p53 signaling pathway, the PI3K-Akt signaling pathway, and the estrogen signaling pathway. The molecular docking showed that quercetin, kaempferol, and 5 critical targets had good results regarding the binding energy. Chromatography showed that DBD contained quercetin and kaempferol compounds, which was consistent with the database prediction results. Based on the above results, we found that the process of DBD interfering POF is closely related to the balance of ESR and AR in TP53-AKT signaling pathway and verified animal experiments. In animal experiments, we have shown that DBD and its active compounds can effectively improve estrus cycle of POF rats, inhibit serum levels of FSH and LH, protein expression levels of Cytochrome C, BAX, p53, and IL6, and promote ovary index, uterine index, serum levels of E2 and AMH, and protein expression levels of AKT1, ESR1, AR, and BCL2. Conclusions. DBD and its active components could treat POF by regulating the balance of ESR and AR in TP53-AKT signaling pathway. [ABSTRACT FROM AUTHOR]

Background. Cancer-related fatigue (CRF) is an increasingly appreciated complication in cancer patients, which severely impairs their quality of life for a long time. Astragali Radix (AR) is a safe and effective treatment to improve CRF, but the related mechanistic studies are still limited. Objective. To systematically analyze the mechanism of AR against CRF by network pharmacology. Methods. TCMSP was searched to obtain the active compounds and targets of AR. The active compound-target (AC-T) network was established and exhibited by related visualization software. The GeneCards database was searched to acquire CRF targets, and the intersection targets with AR targets were used to make the Venny diagram. The protein-protein interaction (PPI) network of intersection targets was established, and further, the therapeutic core targets were selected by topological parameters. The selected core targets were uploaded to Metascape for GO and KEGG analysis. Finally, AutoDock Vina and PyMOL were employed for molecular docking validation. Results. 16 active compounds of AR were obtained, such as quercetin, kaempferol, 7-O-methylisomucronulatol, formononetin, and isorhamnetin. 57 core targets were screened, such as AKT1, TP53, VEGFA, IL-6, and CASP3. KEGG analysis manifested that the core targets acted on various pathways, including 137 pathways such as TNF, IL-17, and the AGE-RAGE signaling pathway. Molecular docking demonstrated that active compounds docked well with the core targets. Conclusion. The mechanism of AR in treating CRF involves multiple targets and multiple pathways. The present study laid a theoretical foundation for the subsequent research and clinical application of AR and its extracts against CRF. [ABSTRACT FROM AUTHOR]

Stroke is a complicated disease with an increasing incidence and a very high mortality rate. A classical Chinese herbal medicine, Dengzhan Shengmai (DZSM), has shown to have therapeutic effects on stroke; however, its chemical basis and molecular mechanism are still unclear. In this study, a systems biology approach was applicable to elucidate the underlying mechanism of action of DZSM on stroke. All the compounds were obtained from databases, and pendant-related targets were obtained from various data platforms, including the TCM Systematic Pharmacology (TCMSP) database, TCM Integrated Database (TCMIP), High Throughput Experimental Reference Database (HERB), Comparative Toxicogenomics Database (CTD), SwissTargetPredicition, and SymMap, The Human Gene Database (GENECARD) and Comparative Toxicogenomics Database (CTD) were used for stroke disease target data, followed by network pharmacology analysis to predict the potential effect of DZSM on stroke. Animal experiments were intended to validate the underlying mechanisms. A total of 846 chemical components were compiled for the targets of DZSM drug, and quercetin, kaempferol, and Wuweizisu C are the highest chemical components compiled from DZSM. Overlapping with 375 disease-specific targets and 149 core targets, the core targets include TNF, IL-6, ALB, and AKT1, which are shown to regulate the disease process from an anti-inflammatory perspective. 198 enrichment messages were obtained by KEGG enrichment analysis, and we believe that the role of the AGE-RAGE signaling pathway in diabetic complications, TNF signaling pathway, and IL-17 signaling pathway is more important. Based on rat experiments, we also demonstrated that DZSM could effectively modulate the inflammation level of brain infarct tissues and effectively alleviate behavioral characteristics. Grouped together, our study suggests that the combination of network pharmacology prediction and experimental validation can provide a useful tool to describe the molecular mechanisms of DZSM in Chinese medicine (TCM). [ABSTRACT FROM AUTHOR]

Background. Poststroke depression (PSD) is the most common and serious neuropsychiatric complication occurring after cerebrovascular accidents, seriously endangering human health while also imposing a heavy burden on society. Nevertheless, it is difficult to control disease progression. Gan-Mai-Da-Zao Decoction (GMDZD) is effective for PSD, but its mechanism of action in PSD is unknown. In this study, we explored the mechanism of action of GMDZD in PSD treatment using network pharmacology and molecular docking. Material and methods. We obtained the active components of all drugs and their targets from the public database TCMSP and published articles. Then, we collected PSD-related targets from the GeneCards and OMIM databases. Cytoscape 3.8.2 was applied to construct PPI and composite target disease networks. In parallel, the DAVID database was used to perform GO and KEGG enrichment analyses to determine the biological processes enriched in the treatment-related drugs in vivo. Finally, molecular docking was used to verify the association between the main active ingredients and their targets. Results. The network pharmacological analysis of GMDZD in PSD revealed 107 active ingredients with important biological effects, including quercetin, luteolin, kaempferol, naringenin, and isorhamnetin. In total, 203 potential targets for the treatment of this disease were screened, including STAT3, JUN, TNF, TPT53, AKT1, and EGFR. These drugs are widely enriched in a series of signaling pathways, such as TNF, HIF-1, and toll-like receptor. Moreover, molecular docking analysis showed that the core active components were tightly bound to their core targets, further confirming their anti-PSD effects. Conclusion. This prospective study was based on the integrated analysis of large data using network pharmacology technology to explore the feasibility of GMDZD for PSD treatment that was successfully validated by molecular docking. It reflects the multicomponent and multitarget characteristics of Chinese medicine and, more importantly, brings hope for the clinical treatment of PSD. [ABSTRACT FROM AUTHOR]

Alpinia oxyphylla (A. oxyphylla) fruit has long been used in traditional Chinese medicine. In our study, the bioactive components of its roots, fruit, and leaves were investigated, and their potential medical value was predicted. The root, fruit, and leaf samples were analyzed using a UPLC-MS/MS system. The mass spectrometry outcomes were annotated by MULTIAQUANT. The "compound-disease targets" were used to construct a pharmacology network. A total of 293, 277, and 251 components were identified in the roots, fruit, and leaves, respectively. The fruit of A. oxyphylla had a higher abundance of flavonols. The roots of A. oxyphylla were enriched in flavonols and phenolic acids. The leaves of A. oxyphylla exhibited high contents of flavonols, phenolic acids, and tannins. Furthermore, network pharmacology analysis showed that flavonoids are the most important effectors in the fruit of A. oxyphylla and phenolic acids are the most important effectors in the roots and leaves. Moreover, the results suggested that the tissues of A. oxyphylla might play a role in the regulation of disease-related genes. The whole plant of A. oxyphylla is rich in natural drug components, and each tissue has high medicinal value. Therefore, comprehensive utilization of A. oxyphylla can greatly improve its economic value. [ABSTRACT FROM AUTHOR]

Radix Astragali and Semen Lepidii (HQ-TLZ) is a commonly used herbal medicine combination for treatment of heart failure, which has a good clinical effect. However, its active components and mechanism of action are not clear, which limits its clinical application and development. In this study, we explored the mechanism of action of HQ-TLZ in the treatment of heart failure based on network pharmacology. We obtained 11 active ingredients and 109 targets from the TCMSP database and SwissTargetPrediction database. Next, we constructed the action network and carried out enrichment analysis. The results showed that HQ-TLZ treatment of heart failure is primarily achieved by regulating the insulin resistance, erbB signaling pathway, PI3K-Akt signaling pathway, and VEGF signaling pathway. After inverse targeting, molecular docking, and literature search, we determined that the equivalent molecular groups of HQ-TLZ in the treatment of heart failure were quercetin and kaempferol. Based on network pharmacology, we reveal the mechanism of action of HQ-TLZ in the treatment of heart failure to a certain extent. At the same time, we determined the composition of the equivalent molecular group. This provides a bridge for the consistency evaluation of natural herbs and molecular compounds, which is beneficial to the development of novel drugs and further research. [ABSTRACT FROM AUTHOR]

Many Bangladeshi medicinal plants have been used to treat Alzheimer's disease and other neurodegenerative diseases. In the present study, the anticholinesterase effects of eight selected Bangladeshi medicinal plant species were investigated. Species were selected based on the traditional uses against CNS-related diseases. Extracts were prepared using a gentle cold extraction method. In vitro cholinesterase inhibitory effects were measured by Ellman's method in 96-well microplates. Blumea lacera (Compositae) and Cyclea barbata (Menispermaceae) were found to have the highest acetylcholinesterase inhibitory (IC50, 150 ± 11 and 176 ± 14 µg/mL, respectively) and butyrylcholinesterase inhibitory effect (IC50, 297 ± 13 and 124 ± 2 µg/mL, respectively). Cyclea barbata demonstrated competitive inhibition, where Blumea lacera showed an uncompetitive inhibition mode for acetylcholinesterase. Smilax guianensis (Smilacaceae) and Byttneria pilosa (Malvaceae) were also found to show moderate AChE inhibition (IC50, 205 ± 31 and 221 ± 2 µg/mL, respectively), although no significant BChE inhibitory effect was observed for extracts from these plant species. Among others, Thunbergia grandiflora (Acanthaceae) and Mikania micrantha (Compositae) were found to display noticeable AChE (IC50, 252 ± 22 µg/mL) and BChE (IC50, 314 ± 15 µg/mL) inhibitory effects, respectively. Molecular docking experiment suggested that compounds 5-hydroxy-3,6,7,3′,4′-pentamethoxyflavone (BL4) and kaempferol-3-O-α-L-rhamnopyranosyl-(1⟶6)-β-D-glucopyranoside (BL5) from Blumea lacera bound stably to the binding groove of the AChE and BChE by hydrogen-bond interactions, respectively. Therefore, these compounds could be candidates for cholinesterase inhibitors. The present findings demonstrated that Blumea lacera and Cyclea barbata are interesting objects for further studies aiming at future therapeutics for Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Endometriosis is a chronic estrogen-dependent inflammatory disorder that negatively affects the quality of life in women. The Wenjing decoction (WJD) is a traditional Chinese medicine that has been shown to have a therapeutic effect on endometriosis. Our study systematically explored the mechanism of WJD against endometriosis using a network pharmacology approach. Potentially bioactive compounds of WJD and their possible targets were retrieved from the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform. The protein-protein interaction network and herbs-compounds-genes multinetwork were constructed using Cytoscape for visualization. Subsequently, the signaling pathways of common targets were retrieved from the Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, and molecular docking was performed using PyRx software. In total, 48 common targets were screened, such as IL6 and ESR1, which were related to inflammation and the endocrine system. The top five bioactive compounds were quercetin, kaempferol, wogonin, beta-sitosterol, and stigmasterol. KEGG enrichment analysis revealed 65 pathways containing inflammatory- and endocrine-related signaling pathways, such as the "TNF signaling pathway" and the "estrogen signaling pathway." Taken together, the results of our network pharmacology analysis predicted that certain active ingredients of WJD might treat endometriosis by regulating inflammation and/or endocrine, which provided references for further understanding and exploration of WJD on endometriosis. [ABSTRACT FROM AUTHOR]

Background. Chronic obstructive pulmonary disease (COPD) is characterized by high morbidity, disability, and mortality, which seriously threatens human life and health. Xixin and Ganjiang are classic herb pairs of Zhongjing Zhang, which are often used to treat COPD in China. However, the substance basis and mechanism of action of Xixin-Ganjiang herb pair (XGHP) in the treatment of COPD remain unclear. Methods. On the website of TCMSP and the DrugBank, effective compounds and targets of XGHP were found. COPD targets were obtained from GeneCards, DisGeNET, and GEO gene chips. Intersecting these databases resulted in a library of drug targets for COPD. Then, intersection targets were used for protein-protein interaction (PPI) and pathway enrichment analysis. Finally, the binding activity between compounds and core genes was evaluated by molecular docking to verify the expression level of PTGS2 and PPARG in rats. Results. Twelve effective compounds and 104 core genes were found in the intersection library, and kaempferol, sesamin, β-sitosterol, PTGS2, and PPARG were particularly prominent in the network analysis. A total of 113 pathways were obtained and enrichment of the TNF signaling pathway, IL-17 signaling pathway, and C-type lectin receptor signaling pathway was particularly obvious. Molecular docking indicated that kaempferol, sesamin, and β-sitosterol were closely related to PTGS2 and PPARG and were superior to aminophylline. Key compounds in XGHP could restrict the expression of PTGS2 in the lung tissues of COPD rats and promote the expression of PPARG. Conclusion. Inhibition of the expression of inflammatory factor PTGS2 and promotion of the expression of PPARG may be an effective target of XGHP in the treatment of COPD. [ABSTRACT FROM AUTHOR]

Background. Huangqi Gegen decoction (HGD), a Chinese herb formula, has been widely used to treat diabetic nephropathy in China, while the pharmacological mechanisms are still unclear. Therefore, the present study aims to explore the underlying mechanism of HGD for treating diabetic nephropathy (DN). Materials and Methods. Traditional Chinese Medicine Systems Pharmacology Database (TCMSP), UniProt, and SwissTargetPrediction databases were used to search the active ingredients and potential targets of HGD. In addition, multiple disease-related databases were used to collect DN-related targets. Common targets of the protein-protein interaction (PPI) network were established using the STRING database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using the DAVID database. At last, AutoDockVina was used to conduct molecular docking verification for the core components and targets. Results. A total of 27 active ingredients and 354 putative identified target genes were screened from HGD, of which 99 overlapped with the targets of DN and were considered potential therapeutic targets. Further analysis showed that the HGD activity of quercetin, formononetin, kaempferol, isorhamnetin, and beta-sitosterol ingredients is possible through VEGFA, IL6, TNF, AKT1, and TP53 targets involved in TNF, toll-like receptors, and MAPK-related pathways, which have anti-inflammatory, antiapoptosis, antioxidation, and autophagy effects, relieve renal fibrosis and renal cortex injury, and improve renal function, thus delaying the development of DN. The molecular docking results showed that quercetin, formononetin, kaempferol, isorhamnetin, beta-sitosterol had a good binding activity with VEGFA, IL6, TNF, AKT1, and TP53. Conclusion. This study demonstrated that HGD might take part in the treatment of DN through multicomponent, multitarget, and multichannel combined action. [ABSTRACT FROM AUTHOR]

Background. The incidence of gout has been rapidly increasing in recent years with the changing of diet. At present, modern medications used in the clinical treatment of gout showed several side effects, such as gastrointestinal damage and the increased risk of cardiovascular disease. The traditional Chinese prescription Simiao Powder (SMP) has a long history in the treatment of acute gouty arthritis (AGA) and has a good curative effect. However, the mechanism and target of its therapeutic effects are still not completely understood. Methods. Potential active compounds (PACs) and targets of SMP were found in the TCMSP database, and the disease target genes related to AGA were obtained by searching CTD, DisGeNET, DrugBank, GeneCards, TTD, OMIM, and PharmGKB disease databases with "acute gouty arthritis" and "Arthritis, Gouty" as keywords, respectively. The network of "Traditional Chinese medicine (TCM)-PACs-potential targets of acute gouty arthritis" was constructed with the Cytoscape 3.7.2 software, and the target genes of acute gouty arthritis were intersected with genes regulated by active compounds of SMP. The resultant common gene targets were input into Cytoscape 3.7.2 software, and the BisoGenet plug-in was used to construct a PPI network. The GO functional enrichment analysis and KEGG pathway enrichment analysis of the intersecting target proteins were performed using R software and corresponding program packages. The molecular docking verification was carried out between the potentially active compounds of SMP and the core target at the same time. Results. 40 active components and 203 targets were identified, of which 95 targets were common targets for the drugs and diseases. GO function enrichment analysis revealed that SMP regulated several biological processes, such as response to lipopolysaccharide and oxidative stress, RNA polymerase II transcription regulator complex, protein kinase complex, and other cellular and molecular processes, including DNA-binding transcription factor binding. Results of KEGG pathway analysis showed that SMP was associated with AGA-related pathways such as interleukin-17 (IL-17), tumor necrosis factor (TNF), p53, and hypoxia-inducible factor 1 (HIF-1) signaling pathways. The results of molecular docking showed that active compounds in SMP exhibited strong binding to five core protein receptors (TP53, FN1, ESR1, CDK2, and HSPA5). Conclusions. Active components of SMP, such as quercetin, kaempferol, wogonin, baicalein, beta-sitosterol, and rutaecarpine, showed therapeutic effects on AGA. These compounds were strongly associated with core target proteins (such as TP53, FN1, ESR1, CDK2, and HSPA5). This study reveals that IL-17, TNF, p53, and HIF-1 signaling pathways mediate the therapeutic effects of SMP on AGA. These findings expand our understanding of the mechanism of SMP in the treatment of AGA. [ABSTRACT FROM AUTHOR]

Objective. To analyze the pharmacological mechanism of the treatment of dry age-related macular degeneration (dry AMD) based on a network pharmacological approach of Shuang Di Shou Zhen Tablets (SDSZT) and to provide a new reference for the current lack of effective treatment of dry AMD. Methods. The main chemical constituents and their targets of Rehmanniae Radix Praeparata, Ligustrum lucidum, Mori Fructus, Paeonia albiflora, Rhizoma Dioscoreae, Alisma orientale, Schisandra chinensis, Radix Polygoni Multiflori Preparata, Ophiopogon japonicus, and Radix Rehmanniae were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and Traditional Chinese Medicine Integrated Database (TCMID). The active ingredients of traditional Chinese medicine were screened according to Absorption, Distribution, Metabolism, and Excretion (ADME), the gene names of the targets of each active ingredient were obtained from the Uniprot database, the main targets of dry AMD were obtained from GeneCards and DisGeNET database, and the protein interaction analysis was performed on the String database. The Metascape database was used to analyze the "drug-component-target" and the biological processes and networks involved, and then, Cytoscape 3.8.1 was used to construct the " SDSZT component-dry AMD target-pathway" network. Results. The main active ingredients of SDSZT for dry AMD treatment are quercetin, kaempferol, luteolin, β-glutamine, β-carotene, etc. And, the core targets are RAC-alpha serine/threonine-protein kinase (AKT1), prostaglandin G/H synthase 1 (PTGS1), tumor necrosis factor (TNF), transcription factor AP-1 (JUN), apoptosis regulator Bcl-2 (BCL2), caspase-3 (CASP3), phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (PIK3CG), androgen receptor (AR), apoptosis regulator BAX (BAX), etc. The biological pathways for the treatment of age-related macular degeneration by SDSZT mainly act on pathways in cancer, fluid shear stress and atherosclerosis, and TNF signaling pathway, and the main function of SDSZT is to regulate intracellular cytokine receptor binding. Conclusion. This study initially reveals the multiconstituent, multitarget, and multipathway mechanism of action of SDSZT in the treatment of dry AMD and provides the basis for the clinical application of SDSZT. [ABSTRACT FROM AUTHOR]

Objective. To study the pharmacological mechanisms of Siwu decoction (SWD) on primary dysmenorrhea (PDM) and verify with molecular docking. Methods. The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) was utilized to acquire the active compounds and their corresponding target genes. The GeneCards database was utilized in the search for target genes that were associated with PDM. The intersection genes from the active target genes of SWD and those associated with PDM represented the active target genes of SWD that act on PDM. The Gene Ontology (GO) function enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were both carried out by RGUI 3.6.1 and Cytoscape 3.6.0 software. Cytoscape was also utilized for creating a compound-target network, and a protein-protein interaction (PPI) network was created through the STRING database. Molecular docking simulations of the macromolecular protein target receptors and their corresponding compounds were performed using AutoDockTool 1.5.6 and AutoDock Vina software. Results. We identified 14 active compounds as well as 97 active target genes of SWD by using the TCMSP. We compared the 97 active target genes of SWD to the 299 target genes related to PDM, and 23 active target genes for SWD that act on PDM which correlated with 11 active compounds were detected. The compound-target network as well as the PPI network were created, in addition to selecting the most essential compounds and their targets in order to create a key compound-target network. The most essential compounds were kaempferol, beta-sitosterol, stigmasterol, and myricanone. The key targets were AKT1, PTGS2, ESR1, AHR, CASP3, and PGR. Lastly, molecular docking was used to confirm binding of the target with its corresponding compound. Conclusion. The pharmacological mechanisms of SWD that act on PDM were investigated, and the active compounds in the SWD for treating PDM were further verified. [ABSTRACT FROM AUTHOR]

Moringa oleifera Lam. is an essential herb used for the treatment of inflammation, diabetes, high blood pressure, and other diseases. In this study, phenolic extracts of M. oleifera leaves were obtained and analyzed. The results showed that the main identifiable phenols were astragalin, chlorogenic acid, isoquercitrin, kaempferitrin, luteolin, quercetin, and rutin. The effects of M. oleifera polyphenol extract (MOPE) on experimental colitis induced by 3% dextran sulfate sodium (DSS) were investigated. The results showed that oral administration of MOPE significantly alleviated the symptoms of DSS-induced colitis. MOPE significantly reduced weight loss, the disease activity index, colon shortening, and mucosal damage. In addition, MOPE attenuated the infiltration of CD3+ T cells, CD177+ neutrophils, and F4/80+ macrophages and significantly inhibited the secretion of IL-6 and TNF-α. After the MOPE administration, the expression of proteins associated with the NF-κB signaling pathway changed. Specifically, compared with that of the DSS group, the protein expression of NF-κB p65 and p-IκBα was downregulated, and the expression of IκBα was upregulated. This study revealed the anti-inflammatory effects and mechanisms of MOPE in the colon, indicating its potential use in preventing inflammation-driven diseases. [ABSTRACT FROM AUTHOR]

Phragmanthera capitata was reported to possess many biological properties making it a good candidate for the formulation of a phytomedicine with multiple effects. In this work, we studied some factors likely to modify these therapeutic properties with the aim to contribute to its standardization as an improved traditional medicine. P. capitata parasitizing Persea americana, Psidium guajava, and Podocarpus mannii were harvested at three phenological stages (vegetative, flowering, and fruiting stages). The extracts were prepared by maceration in n-hexane, ethyl acetate, ethanol, methanol, and distilled water. The total phenolic, flavonoid, flavonol, and tannin contents were measured using appropriate methods. The antioxidant potential of extracts was investigated using TAC, DPPH scavenging, and FRAP methods. The α-amylase and α-glucosidase inhibitory activities of extracts were determined using enzymatic methods. The ethyl acetate extracts with the best phenolic content were subjected to HPLC analysis. The extraction yields were higher with methanol. The ethyl acetate extract of P. capitata harvested from P. guajava showed a stable HPLC profile during the development of the plant, while extracts from the plant collected from P. americana and P. mannii showed both qualitative and quantitative variations according to phonological stages of the plant. The inhibition of α-amylase was more pronounced for P. capitata harvested from P. guajava, decreasing during flowering and fruiting, while inhibition of α-glucosidase was not influenced by the phenological stage and the host of the plant. The α-amylase inhibitors were better extracted by ethyl acetate and those of α-glucosidase by ethanol or methanol. The phenolic contents and antioxidant properties of the extracts were influenced by the phenological stage of P. capitata and its hosts. These results suggest that it is preferable to harvest P. capitata during flowering or during fruiting stages on any host. None of the used solvents permitted an optimal extraction of active principles form P. capitata, suggesting that the mixture of solvents must be considered in further studies. [ABSTRACT FROM AUTHOR]

Prunella vulgaris (PV) has a long history of application in traditional Chinese and Western medicine as a remedy for the treatment of subacute thyroiditis (SAT). This study applied network pharmacology to elucidate the mechanism of the effects of PV against SAT. Components of the potential therapeutic targets of PV and SAT-related targets were retrieved from databases. To construct a protein-protein interaction (PPI) network, the intersection of SAT-related targets and PV-related targets was input into the STRING platform. Gene ontology (GO) analysis and KEGG pathway enrichment analysis were carried out using the DAVID database. Networks were constructed by Cytoscape for visualization. The results showed that a total of 11 compounds were identified according to the pharmacokinetic parameters of ADME. A total of 126 PV-related targets and 2207 SAT-related targets were collected, and 83 overlapping targets were subsequently obtained. The results of the KEGG pathway and compound-target-pathway (C-T-P) network analysis suggested that the anti-SAT effect of PV mainly occurs through quercetin, luteolin, kaempferol, and beta-sitosterol and is most closely associated with their regulation of inflammation and apoptosis by targeting the PIK3CG, MAPK1, MAPK14, TNF, and PTGS2 proteins and the PI3K-Akt and TNF signaling pathways. The study demonstrated that quercetin, luteolin, kaempferol, and beta-sitosterol in PV may play a major role in the treatment of SAT, which was associated with the regulation of inflammation and apoptosis, by targeting the PI3K-Akt and TNF signaling pathways. [ABSTRACT FROM AUTHOR]

Gu-tong formula (GTF) has achieved good curative effects in the treatment of cancer-related pain. However, its potential mechanisms have not been explored. We used network pharmacology and molecular docking to investigate the molecular mechanism and the effective compounds of the prescription. Through the analysis and research in this paper, we obtained 74 effective compounds and 125 drug-disease intersection targets to construct a network, indicating that quercetin, kaempferol, and β-sitosterol were possibly the most important compounds in GTF. The key targets of GTF for cancer-related pain were Jun proto-oncogene (JUN), mitogen-activated protein kinase 1 (MAPK1), and RELA proto-oncogene (RELA). 2204 GO entries and 148 pathways were obtained by GO and KEGG enrichment, respectively, which proved that chemokine, MAPK, and transient receptor potential (TRP) channels can be regulated by GTF. The results of molecular docking showed that stigmasterol had strong binding activity with arginine vasopressin receptor 2 (AVPR2) and C-X3-C motif chemokine ligand 1 (CX3CL1) and cholesterol was more stable with p38 MAPK, prostaglandin-endoperoxide synthase 2 (PTGS2), and transient receptor potential vanilloid-1 (TRPV1). In conclusion, the therapeutic effect of GTF on cancer-related pain is based on the comprehensive pharmacological effect of multicomponent, multitarget, and multichannel pathways. This study provides a theoretical basis for further experimental research in the future. [ABSTRACT FROM AUTHOR]

Background. Diabetic retinopathy (DR) includes a series of typical lesions affected by retinal microvascular damage caused by diabetes mellitus (DM), which not only seriously damages the vision, affecting the life's quality of patients, but also brings a considerable burden to the family and society. Astragalus Membranaceus (AM) is a commonly used medicine in clinical therapy of eye disorders in traditional Chinese medicine (TCM). In recent years, it is also used for treating DR, but the specific mechanism is unclear. Therefore, this study explores the potential mechanism of AM in DR treatment by using network pharmacology. Methods. Based on the oral bioavailability (OB) and drug likeness (DL) of two ADME (absorption, distribution, metabolism, excretion) parameters, Traditional Chinese Medicine Systems Pharmacology Database (TCMSP), Swiss Target Prediction platform, GeneCards, and OMIM database were used to predict and screen the active compounds of AM, the core targets of AM in DR treatment. The Metascape data platform was used to perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis on the core targets. Results. 24 active compounds were obtained, such as quercetin, kaempferol, and astragaloside IV. There were 169 effective targets of AM in DR treatment, and the targets were further screened and finally, 38 core targets were obtained, such as VEGFA, AKT1, and IL-6. EGFR tyrosine kinase inhibitor resistance, AGE-RAGE signaling pathway in diabetic complications, PI3K-Akt signaling pathway, and other metabolic pathways participated in oxidative stress, cell apoptosis, angiogenesis signal transduction, inflammation, and other biological processes. Conclusion. AM treats DR through multiple compounds, multiple targets, and multiple pathways. AM may play a role in the treatment of DR by targeting VEGFA, AKT1, and IL-6 and participating in oxidative stress, angiogenesis, and inflammation. [ABSTRACT FROM AUTHOR]

Aim of the Study. To study the mechanism of Compound-Xueshuantong Capsule in diabetic retinopathy treatment based on network pharmacology. Materials and Methods. The components with oral bioavailability ≥30% and drug similarity ≥0.18 were screened by the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform (TCMSP), and the effective grouping of Compound-Xueshuantong Capsule was obtained. At the same time, the targets of each drug active component in the Compound-Xueshuantong Capsule were obtained by searching the TCMSP. The effective components and targets of the Compound-Xueshuantong Capsule were annotated by the UniProt database, and the disease treatment targets were searched by the GeneCards database. The disease treatment target is intersected with the drug target and the Wayne diagram is drawn by VennDiagram. The active ingredient targets of the intersection and Compound-Xueshuantong Capsule were inputted into Cytoscape 3.7.2 software to construct the active ingredient-target-disease interaction network. The above targets were inputted into the String database for protein-protein interaction network prediction. Finally, by using the DAVID database, GO and KEGG enrichment analysis was carried out to reveal the potential signal pathway of the Compound-Xueshuantong Capsule in diabetic retinopathy treatment. Results. 93 active components of the Compound-Xueshuantong Capsule and 92 targets for treating diabetic retinopathy were screened. The main active components of the Compound-Xueshuantong Capsule in treating diabetic retinopathy were quercetin, luteolin, kaempferol, beta-sitosterol, isorhamnetin, and tanshinone IIa. The effect of the Compound-Xueshuantong Capsule on diabetic retinopathy may be related to IL6, EFGR, CASP3, and VEGFA. In addition, the treatment of diabetic retinopathy mainly involves in the regulation of nuclear receptors and transcription factors in vivo. The target of the Compound-Xueshuantong Capsule in diabetic retinopathy treatment is significantly enriched in the AGE-RAGE signal pathway, TNF signal pathway, HIF-1 signal pathway, and VEGF signal pathway in diabetic complications. Conclusion. Compound-Xueshuantong Capsule can treat diabetic retinopathy through multitarget, multipathway, and multipathway regulation of the biomolecular network. The potential biological mechanism of the Compound-Xueshuantong Capsule in diabetic retinopathy treatment may be related to the AGE-RAGE signal pathway, TNF signal pathway, HIF-1 signal pathway, and VEGF signal pathway in diabetic complications, but these findings still need to be confirmed by further clinical research. [ABSTRACT FROM AUTHOR]

Sanmiao pill (SMP), a Chinese traditional formula, had been used to treat gouty arthritis (GA). However, the active compounds and underlying mechanism remained unclear. Hence, network pharmacology and molecular docking were utilized to explore bioactive compounds and potential mechanism of action of SMP in treating GA. In the study, the compounds of SMP, corresponding targets, and GA-related targets were mined from various pharmacological databases. Then, herb-compound-target, compound-target, PPI, and target-pathway networks were constructed. Ultimately, molecular docking was carried out to verify the predicted results. The results indicated that 47 active compounds, 338 targets, and 144 disease targets were collected. Network analysis implied that Phellodendron chinense Schneid. played a vital role in the whole formula. Moreover, 7 compounds (quercetin, kaempferol, wogonin, rutaecarpine, baicalein, beta-sitosterol, and stigmasterol) and 4 targets (NFKB1, RELA, MAPK1, and TNF) might be the kernel compounds and targets of SMP against GA. According to GOBP and KEGG pathway enrichment analysis and target-pathway network, SMP might exert a therapeutic role in GA by regulating numerous biological processes and pathways, including lipopolysaccharide-mediated signaling pathway, positive regulation of transcription, Toll-like receptor signaling pathway, JAK-STAT signaling pathway, NOD-like receptor signaling pathway, and MAPK signaling pathway. The results of molecular docking showcased that 11 pairs of compound with targets had tight binding strength. Thereinto, 4 compounds of MAPK1 and 5 compounds of NFKB1 possessed a better combination, suggesting that MAPK1 and NFKB1 might be considered as therapeutic targets in treatment of GA. This study verified that SMP had synergistic effect on GA by multicomponents, multitargets, and multipathways. [ABSTRACT FROM AUTHOR]

Spinal cord injury (SCI) is a serious condition that results in disability and has a high morbidity rate; its treatment is very difficult. Although troxerutin and cerebroprotein hydrolysate (TCH) injections have been extensively used in clinics in China for the treatment of traumatic brain injury (TBI) and cerebral stroke, the potential efficacy of TCH injection in the treatment of SCI has never been revealed. In this study, the effects of administering TCH injections on neurological recovery in post-SCI rats were first tested with regard to the behavior and histology; subsequently, the specific expression profile of mRNAs and long noncoding RNAs (LncRNAs) in their spinal cords were conducted using RNA sequencing (RNA-seq). The LncRNA-mRNA networks were also elucidated. After SCI, we found that TCH injection with the right dose is effective for the recovery of locomotion function and repairing of the damaged tissue in the spinal cord; TCH injection is also discovered to have a role in the regulation of 443 differentially expressed genes (DEGs) and 27 differentially expressed LncRNAs (DELs) that are identified to have multiple functions, including locomotion, blood vessel morphogenesis, thiamine metabolism, Hippo signaling pathway, and axon guidance, by applying the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and Gene Ontology (GO) analysis. In addition, it is revealed that, after SCI, the highly expressed LncRNA AABR07071383.1 in the post-SCI cis/trans-regulates the expression of mRNA Acpp mRNA that encodes a key enzyme involved in the metabolic process of thiamine in the abirritation of the dorsal root ganglion (DRG), which implies that TCH injection may be more effective when administered with benfotiamine (a common treatment drug). [ABSTRACT FROM AUTHOR]

Aging is a main risk factor for a number of debilitating diseases and contributes to an increase in mortality. Previous studies have shown that Ginkgo biloba extract (EGb) can prevent and treat aging-related diseases, but its pharmacological effects need to be further clarified. This study aimed to propose a network pharmacology-based method to identify the therapeutic pathways of EGb for aging. The active components of EGb and targets of sample chemicals were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) database. Information on aging-related genes was obtained from the Human Ageing Genomic Resources database and JenAge Ageing Factor Database. Subsequently, a network containing the interactions between the putative targets of EGb and known therapeutic targets of aging was established, which was used to investigate the pharmacological mechanisms of EGb for aging. A total of 24 active components, 154 targets of active components of EGb, and 308 targets of aging were obtained. Network construction and pathway enrichment were conducted after data integration. The study found that flavonoids (quercetin, luteolin, and kaempferol) and beta-sitosterol may be the main active components of EGb. The top eight candidate targets, namely, PTGS2, PPARG, DPP4, GSK3B, CCNA2, AR, MAPK14, and ESR1, were selected as the main therapeutic targets of EGb. Pathway enrichment results in various pathways were associated with inhibition of oxidative stress, inhibition of inflammation, amelioration of insulin resistance, and regulation of cellular biological processes. Molecular docking results showed that PPARG had better binding capacity with beta-sitosterol, and PTGS2 had better binding capacity with kaempferol and quercetin. The main components of EGb may act on multiple targets, such as PTGS2, PPARG, DPP4, and GSK3B, to regulate multiple pathways, and play an antiaging role by inhibiting oxidative stress, inhibiting inflammation, and ameliorating insulin resistance. [ABSTRACT FROM AUTHOR]

Objective. To analyze the active compounds, potential targets, and diseases of JianPi Fu Recipe (JPFR) based on network pharmacology and bioinformatics and verify the potential biological function and mechanism of JPFR in vitro and in vivo. Methods. Network pharmacology databases including TCMSP, TCM-PTD, TCMID, and DrugBank were used to screen the active compounds and potential drug targets of JPFR. Cytoscape 3.7 software was applied to construct the interaction network between active compounds and potential targets. The DAVID online database analysis was performed to investigate the potential effective diseases and involved signaling pathways according to the results of the GO function and KEGG pathways enrichment analysis. To ensure standardization and maintain interbatch reliability of JPFR, High Performance Liquid Chromatography (HPLC) was used to establish a "chemical fingerprint." For biological function validation, the effect of JPFR on the proliferation and migration of CRC cells in vitro was investigated by CCK-8 and transwell and wound healing assay, and the effect of JPFR on the growth and metastasis of CRC cells in vivo was detected by building a lung metastasis model in nude mice and in vivo imaging. For the potential mechanism validation, the expressions of MALAT1, PTBP-2, and β-catenin in CRC cells and transplanted CRC tumors were detected by real-time PCR, western blot, and immunohistochemical staining analysis. Results. According to the rules of oral bioavailability (OB) > 30% and drug-likeness (DL) > 0.18, 244 effective compounds in JPFR were screened out, as well as the corresponding 132 potential drug targets. By the analysis of DAVID database, all these key targets were associated closely with the cancer diseases such as prostate cancer, colorectal cancer, bladder cancer, small cell lung cancer, pancreatic cancer, and hepatocellular carcinoma. In addition, multiple signaling pathways were closely related to JPFR, including p53, Wnt, PI3K-Akt, IL-17, HIF-1, p38-MAPK, NF-κB, PD-L1 expression and PD-1 checkpoint pathway, VEGF, JAK-STAT, and Hippo. The systematical analysis showed that various active compounds of JPFR were closely connected with Wnt/β-catenin, EGFR, HIF-1, TGFβ/Smads, and IL6-STAT3 signaling pathway, including kaempferol, isorhamnetin, calycosin, quercetin, medicarpin, phaseol, spinasterol, hederagenin, beta-sitosterol, wighteone, luteolin, and isotrifoliol. For in vitro experiments, the migration and growth of human CRC cells were inhibited by the JPFR extract in a dose-dependent way, and the expression of MALAT1, PTBP-2, β-catenin, MMP7, c-Myc, and Cyclin D1 in CRC cells were downregulated by the JPFR extract in a dose-dependent way. For in vivo metastasis experiments, the numbers of lung metastasis were found to be decreased by the JPFR extract in a dose-dependent manner, and the expressions of metastasis-associated genes including MALAT1, PTBP-2, β-catenin, and MMP7 in the lung metastases were downregulated dose dependently by the JPFR extract. For the orthotopic transplanted tumor experiments, the JPFR extract could inhibit the growth of orthotopic transplanted tumors and downregulate the expression of c-Myc and Cyclin D1 in a dose-dependent manner. Moreover, the JPFR extract could prolong the survival time of tumor-bearing mice in a dose-dependent manner. Conclusions. Through effective network pharmacology analysis, we found that JPFR contains many effective compounds which may directly target cancer-associated signaling pathways. The in vitro and in vivo experiments further confirmed that JPFR could inhibit the growth and metastasis of CRC cells by regulating β-catenin signaling-associated genes or proteins. [ABSTRACT FROM AUTHOR]

Background. HeChan tablet (HCT) is a traditional Chinese medicine preparation extensively prescribed to treat lung cancer in China. However, the pharmacological mechanisms of HCT on lung cancer remain to be elucidated. Methods. A comprehensive network pharmacology-based strategy was conducted to explore underlying mechanisms of HCT on lung cancer. Putative targets and compounds of HCT were retrieved from TCMSP and BATMAN-TCM databases; related genes of lung cancer were retrieved from OMIM and DisGeNET databases; known therapeutic target genes of lung cancer were retrieved from TTD and DrugBank databases; PPI networks among target genes were constructed to filter hub genes by STRING. Furthermore, the pathway and GO enrichment analysis of hub genes was performed by clusterProfiler, and the clinical significance of hub genes was identified by The Cancer Genome Atlas. Result. A total of 206 compounds and 2,433 target genes of HCT were obtained. 5,317 related genes of lung cancer and 77 known therapeutic target genes of lung cancer were identified. 507 unique target genes were identified among HCT-related genes of lung cancer and 34 unique target genes were identified among HCT-known therapeutic target genes of lung cancer. By PPI networks, 11 target genes AKT1, TP53, MAPK8, JUN, EGFR, TNF, INS, IL-6, MYC, VEGFA, and MAPK1 were identified as major hub genes. IL-6, JUN, EGFR, and MYC were shown to associate with the survival of lung cancer patients. Five compounds of HCT， quercetin, luteolin, kaempferol, beta-sitosterol, and baicalein were recognized as key compounds of HCT on lung cancer. The gene enrichment analysis implied that HCT probably benefitted patients with lung cancer by modulating the MAPK and PI3K-Akt pathways. Conclusion. This study predicted pharmacological and molecular mechanisms of HCT against lung cancer and could pave the way for further experimental research and clinical application of HCT. [ABSTRACT FROM AUTHOR]

This study developed a method for simultaneous determination of 13 elements of Semen Cuscutae (quercitrin, quercetin, hyperoside, caffeic acid, chlorogenic acid, luteolin, apigenin, kaempferol, isoquercitrin, cryptochlorogenic acid, isorhamnetin-3-O-glucoside, astragalin, and rutin) in rat plasma using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) in the negative MRM mode. The analytes were analyzed with CORTECS®C18 column (4.6 × 150 mm, 2.7 μm) with mobile phases consisting of 0.1% formic acid in water (A) and acetonitrile (B). The intra- and interday precision of the target compounds were expressed as relative standard deviation (RSD) in the range of 0.5%–10.4%, and the accuracy of the target compounds was expressed as relative error (RE) not exceeding ±14.5% for all analytes. In the meantime, the extraction recovery of the target compounds in plasma samples ranged from 87.4% to 106.2% and matrix effect from 81.0% to 115.5%. The established method was successfully accomplished for the pharmacokinetic study of the analytes in rat plasma samples following oral administration of Semen Cuscutae extract, and the pharmacokinetic parameters of seven compounds were obtained. [ABSTRACT FROM AUTHOR]

Tetrastigma hemsleyanum Diels et Gilg (T. hemsleyanums) is a kind of traditional folk medicinal plant which has been used widely in China for its antivirus, antitumor, and other clinical effects. In this study, ultra-high performance liquid chromatography coupled with hybrid quadrupole-orbitrap mass spectrometry (UPLC-Q-Exactive/MS) was utilized to analyze the chemical constituents of T. hemsleyanums. Fifty-one constituents were clarified, including flavonoids, anthraquinones, esters, fatty acids, phenols, and catechins. In the subsequent quantitative analysis, the contents of ten compounds of rutin, kaempferol, astragalin, quercitrin, quercetin, vitexin-rhamnoside, isorhamnetin, vitexin, emodin-8-O-β-D-glucoside, and isoquercetin in 18 batches of T. hemsleyanums collected from different places of cultivation were determined. Meanwhile, anti-influenza virus bioactivity in vitro of the above samples was detected with Gaussia Luciferase viral titer assay. It was found that the antiviral bioactivity varied from batches to batches in accordance with content difference of the chemical constituents in T. hemsleyanums. Correlation analysis was performed with SPSS software for the association between LC-MS chemometrics and bioactivity of influenza virus inhibition, and 8 constituents of flavonoids showed positive correlation coefficient, which may provide a valuable clue for searching potential antiviral components in T. hemsleyanums. [ABSTRACT FROM AUTHOR]

Here we report the evaluation of the antiretroviral effect of two flavonoid 7-O-glucosides, herbacitrin (1) and gossypitrin (2), together with quercetin (3), a well-studied flavonol. Antiviral activity of the flavonoids was assessed by analyzing HIV-1 p24 core protein levels in the supernatants of HIV-1 infected MT-4 and MT-2 cell cultures. The compounds showed mild to weak cytotoxic activities on the host cells; herbacitrin was the strongest in this regard (CC50=27.8 and 63.64 μM on MT-4 and MT-2 cells, respectively). In nontoxic concentrations, herbacitrin and quercetin reduced HIV-1 replication, whereas gossypitrin was ineffective. Herbacitrin was found to inhibit reverse transcriptase at 21.5 μM, while it was a more potent integrase inhibitor already active at 2.15 μM. Therefore, our observations suggest that herbacitrin exerts antiretroviral activity through simultaneously acting on these two targets of HIV-1 and that integrase inhibition might play a major role in this activity. [ABSTRACT FROM AUTHOR]

Objective. To predict and explore the potential mechanism of Yinchensini decoction (YCSND) based on systemic pharmacology. Method. TCMSP database was searched for the active constituents and related target proteins of YCSND. Cytoscape 3.5.1 was used to construct the active ingredient-target interaction of YCSND and network topology analysis, with STRING online database for protein-protein interaction (PPI) network construction and analysis; and collection from the UniProt database of target protein gene name, with the DAVID database for the gene ontology (GO) functional analysis, KEGG pathway enrichment analysis mechanism and targets of YCSND. Results. The results indicate the core compounds of YCSND, namely, kaempferol, 7-Methoxy-2-methyl isoflavone, and formononetin. And its core targets are prostaglandin G/H synthase 2, estrogen receptor, Calmodulin, heat shock protein HSP 90, etc. PPI network analysis shows that the key components of the active ingredients of YCSND are JUN, TP53, MARK1, RELA, MYC, and so on. The results of the GO analysis demonstrate that extracellular space, cytosol, and plasma membrane are the main cellular components of YCSND. Its molecular functions are mainly acting on enzyme binding, protein heterodimerization activity, and drug binding. The biological process of YCSND is focused on response to drug, positive regulation of transcription from RNA polymerase II promoter, the response to ethanol, etc. KEGG results suggest that the pathways, including pathways in cancer, hepatitis B, and pancreatic cancer, play a key role in YCSND. Conclusion. YCSND exerts its drug effect through various signaling pathways and acts on kinds of targets. By system pharmacology, the potential role of drugs and the mechanism of action can be well predicted. [ABSTRACT FROM AUTHOR]

Galactites is a genus of flowering plants belonging to Asteraceae family. This genus is mainly represented by the Galactites elegans (All.) Nyman ex Soldano, the milky thistle, a plant of Mediterranean origin. Galactites elegans is consumed as a monofloral boar thistle honey. Chromatography separation of CHCl3 and n-BuOH extracts of aerial parts of G. elegans led to isolation of 18 pure compounds. Their structures were elucidated by 1D-and 2D-NMR spectroscopy and confirmed by mass spectrometry analysis. Sinapic aldehyde, abietin, chlorogenic acid, neochlorogenic acid, 8α-hydroxypinoresinol, 9α-hydroxypinoresinol, pinoresinol, 4-ketopinoresinol, nortrachelogenin, and erythro-guaiacylglycerol-β-O-4′-dihydroconiferyl alcohol were isolated from CHCl3 extract, while luteolin 4′-O-glucuronide, naringenin-7-O-neohesperidoside, kaempferol-3-O-α-L-rhamnopyranosyl-(1→6)-β-D-glucopyranoside, apigenin-7-O-α-L-rhamnopyranosyl-(1→6)-β-D-glucopyranoside, quercitrin, quercetin-3-O-α-L-rhamnopyranosyl-(1→6)-β-D-glucopyranoside, ciwujiatone, and nortrachelogenin-4,4′-di-O-β-D-glucopyranoside were obtained from n-BuOH extract. The majority of isolated compounds displayed a significant antioxidant potential in vitro test (DPPH). The ability of compounds to reduce the level of peroxides in control and BHP-treated Jurkat cells was studied. The lignan derivatives were also able to reduce at 50 μM the basal level of peroxides in Jurkat cells as well as counteract peroxide increase induced by BHP treatment. Particularly 8α-hydroxypinoresinol was the most active showing 70% of peroxide level inhibition. [ABSTRACT FROM AUTHOR]

Brazilian ginseng, including Pfaffia townsendii, is used in popular medicine as a natural anti-inflammatory, tonic, analgesic, and antidiabetic agent. In this study, we investigated the chemical composition and evaluated the antioxidant and anti-inflammatory activities of the P. townsendii ethanolic extract as well as the major isolated glycoside flavonoids tiliroside and patuletin 3-O-β-D-glucopyranoside. Chromatographic techniques and spectroscopic analysis were used for the isolation and identification of the major compounds. The antioxidant potential was determined through DPPH and ORAC-FL assays. The total phenolic content was measured using Folin-Ciocalteu reagent. The anti-inflammatory activity was determined based on a model of paw edema and carrageenan- (Cg-) induced pleurisy. We identified three phenolic acids, one carboxylic acid and two flavonoids, patuletin 3-O-β-D-glucopyranoside, and tiliroside. The ethanol crude extracts, partitions and isolated flavonoids (4581 μmol of Trolox equivalents/g of extract in ORAC and a SC50 of approximately 31.9 μg/mL in the DPPH assay) demonstrated antioxidant activity, and the ethanolic extract as well as isolated flavonoids inhibited paw edema induced by Cg and leukocyte migration in the Cg-induced pleurisy model. The extract, tiliroside, and patuletin 3-O-β-D-glucopyranoside obtained from P. townsendii have therapeutic potential against oxidative stress-related and inflammatory disorders. [ABSTRACT FROM AUTHOR]