scholarly journals A Network Pharmacology Approach to Uncover the Molecular Mechanisms of Herbal Formula Ban-Xia-Xie-Xin-Tang

2018 ◽  
Vol 2018 ◽  
pp. 1-22 ◽  
Author(s):  
Ming Yang ◽  
Jialei Chen ◽  
Liwen Xu ◽  
Xiufeng Shi ◽  
Xin Zhou ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Synergistic Effects ◽  
Network Pharmacology ◽  
Disease Genes ◽  
Traditional Theory ◽  
Therapeutic Effects ◽  
Proximity Analysis ◽  
Path Distance ◽  
Therapeutic Mechanisms ◽  
Shortest Path Distance

Ban-Xia-Xie-Xin-Tang (BXXXT) is a classical formula from Shang-Han-Lun which is one of the earliest books of TCM clinical practice. In this work, we investigated the therapeutic mechanisms of BXXXT for the treatment of multiple diseases using a network pharmacology approach. Here three BXXXT representative diseases (colitis, diabetes mellitus, and gastric cancer) were discussed, and we focus on in silico methods that integrate drug-likeness screening, target prioritizing, and multilayer network extending. A total of 140 core targets and 72 representative compounds were finally identified to elucidate the pharmacology of BXXXT formula. After constructing multilayer networks, a good overlap between BXXXT nodes and disease nodes was observed at each level, and the network-based proximity analysis shows that the relevance between the formula targets and disease genes was significant according to the shortest path distance (SPD) and a random walk with restart (RWR) based scores for each disease. We found that there were 22 key pathways significantly associated with BXXXT, and the therapeutic effects of BXXXT were likely addressed by regulating a combination of targets in a modular pattern. Furthermore, the synergistic effects among BXXXT herbs were highlighted by elucidating the molecular mechanisms of individual herbs, and the traditional theory of “Jun-Chen-Zuo-Shi” of TCM formula was effectively interpreted from a network perspective. The proposed approach provides an effective strategy to uncover the mechanisms of action and combinatorial rules of BXXXT formula in a holistic manner.

scholarly journals Advancing Drug Discovery and Development from Active Constituents of Yinchenhao Tang, a Famous Traditional Chinese Medicine Formula

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Aihua Zhang ◽  
Hui Sun ◽  
Shi Qiu ◽  
Xijun Wang
Keyword(s):  
Systems Biology ◽  
Drug Discovery ◽  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Molecular Mechanisms ◽  
Synergistic Effects ◽  
Molecular Networks ◽  
Agile Development ◽  
Therapeutic Effects ◽  
Systematic Analysis

Traditional Chinese medicine (TCM) formula has been playing a very important role in health protection and disease control for thousands of years. Guided by TCM syndrome theories, formula are designed to contain a combination of various kinds of crude drugs that, when combined, will achieve synergistic efficacy. However, the precise mechanism of synergistic action remains poorly understood. One example is a famous TCM formula Yinchenhao Tang (YCHT), whose efficacy in treating hepatic injury (HI) and Jaundice syndrome, has recently been well established as a case study. We also conducted a systematic analysis of synergistic effects of the principal compound using biochemistry, pharmacokinetics and systems biology, to explore the key molecular mechanisms. We had found that the three component (6,7-dimethylesculetin (D), geniposide (G), and rhein (R)) combination exerts a more robust synergistic effect than any one or two of the three individual compounds by hitting multiple targets. They can regulate molecular networks through activating both intrinsic and extrinsic pathways to synergistically cause intensified therapeutic effects. This paper provides an overview of the recent and potential developments of chemical fingerprinting coupled with systems biology advancing drug discovery towards more agile development of targeted combination therapies for the YCHT.

scholarly journals Identification of Active Compounds of Mahuang Fuzi Xixin Decoction and Their Mechanisms of Action by LC-MS/MS and Network Pharmacology

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Xiao Liang ◽  
Chang-Shun Liu ◽  
Ting Xia ◽  
Qing-Fa Tang ◽  
Xiao-Mei Tan
Keyword(s):  
Signaling Pathways ◽  
Bioactive Compounds ◽  
Cell Receptor ◽  
Mechanisms Of Action ◽  
Network Pharmacology ◽  
Therapeutic Effects ◽  
Active Compounds ◽  
Beneficial Effects ◽  
T Cell Receptor Signaling ◽  
Therapeutic Mechanisms

The decoction is an important dosage form of traditional Chinese medicine (TCM) administration. The Mahuang Fuzi Xixin decoction (MFXD) is widely used to treat allergic rhinitis (AR) in China. However, its active compounds and therapeutic mechanisms are unclear. The aim of this study was to establish an integrative method to identify the bioactive compounds and reveal the mechanisms of action of MFXD. LC-MS/MS was used to identify the compounds in MFXD, followed by screening for oral bioavailability. TCMSP, BindingDB, STRING, DAVID, and KEGG databases and algorithms were used to gather information. Cytoscape was used to visualize the networks. Twenty-four bioactive compounds were identified, and thirty-seven predicted targets of these compounds were associated with AR. DAVID analysis suggested that these compounds exert their therapeutic effects by modulating the Fc epsilon RI, B-cell receptor, Toll-like receptor, TNF, NF-κB, and T-cell receptor signaling pathways. The PI3K/AKT and cAMP signaling pathways were also implicated. Ten of the identified compounds, quercetin, pseudoephedrine, ephedrine, β-asarone, methylephedrine, α-linolenic acid, cathine, ferulic acid, nardosinone, and higenamine, seemed to account for most of the beneficial effects of MFXD in AR. This study showed that LC-MS/MS followed by network pharmacology analysis is useful to elucidate the complex mechanisms of action of TCM formulas.

scholarly journals A Network Pharmacology-Based Approach for Exploring Key Active Compounds and Pharmacological Mechanisms of Tangshen Formula for Treatment of Diabetic Nephropathy

2021 ◽  
Vol 2021 ◽  
pp. 1-17
Author(s):  
Weie Zhou ◽  
Xuefeng Zhou ◽  
Yuan Zhang ◽  
Yuyang Wang ◽  
Wenjie Wu ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Synergistic Effects ◽  
Mapk Signaling ◽  
Network Pharmacology ◽  
Active Compounds ◽  
Promising Source ◽  
Tangshen Formula ◽  
Compound Target

Diabetic nephropathy (DN) is one of the common and severe microvascular complications of diabetes mellitus (DM). The occurrence and development of DN are related to multiple factors in the human body, which makes DN a complex disease, and the pathogeneses of DN have not yet been fully illustrated. Furthermore, DN lacks effective drugs for treatment nowadays. Chinese herbal medicine (CHM) often shows the feature of multicomponents, multitargets, multipathways, and synergistic effects and shows a promising source of new therapeutic drugs for DN. As a CHM, Tangshen Formula (TSF) was used to treat DN patients in China. However, its bioactive compounds and holistic pharmacological mechanisms on DN are both unclear. A network pharmacology approach was firstly applied to explore multiple active compounds and multiple key pharmacological mechanisms for TSF treating DN by drug-targeted interaction databases, herb-compound-target network, protein-protein interaction network, compound-target-pathway network, and analysis methods. And the results showed that TSF have the characteristic of multicomponents, multitargets, multipathways, and synergistic effects for treating DN. The quercetin, naringenin, kaempferol, and isorhamnetin as key active compounds and the PI3K-Akt signaling pathway, TNF signaling pathway, nonalcoholic fatty liver disease (NAFLD), focal adhesion, rap1 signaling pathway, T cell receptor signaling pathway, MAPK signaling pathway, and insulin resistance as the key molecular mechanisms play important roles in TSF treating DN. Moreover, quercetin, naringenin, kaempferol, and isorhamnetin were successfully detected in TSF by the UHPLC-MS/MS analysis method. And their concentrations were 0.224, 8.295, 0.0564, and 0.0879 mg·kg-1, respectively. The present findings not only provide new insights for a deeper understanding of the constituent basis and pharmacology of TSF but also provide guidance for further pharmacological studies on TSF.

scholarly journals Apomorphine induces mitochondrial-dysfunction-dependent apoptosis in choriocarcinoma

Reproduction ◽  
2020 ◽  
Vol 160 (3) ◽  
pp. 367-377
Author(s):  
Jin-Young Lee ◽  
Jiyeon Ham ◽  
Whasun Lim ◽  
Gwonhwa Song
Keyword(s):  
Molecular Mechanisms ◽  
Drug Repositioning ◽  
Synergistic Effects ◽  
Therapeutic Effects ◽  
Antitumor Effects ◽  
Apoptosis Pathway ◽  
Atp Production ◽  
Intrinsic Apoptosis Pathway ◽  
Choriocarcinoma Cells ◽  
Energy Deprivation

Apomorphine is a derivative of morphine that is used for the treatment of Parkinson’s disease because of its effects on the hypothalamus. Therapeutic effects of apomorphine have also been reported for various neurological diseases and cancers. However, the molecular mechanisms of the antitumor effects of apomorphine are not clear, especially with respect to choriocarcinoma. This is the first study to elucidate the anticancer effects of apomorphine on choriocarcinoma. We found that apomorphine suppressed the viability, proliferation, ATP production, and spheroid formation of JEG3 and JAR choriocarcinoma cells. Moreover, apomorphine activated the intrinsic apoptosis pathway by activating caspases and inhibited the production of anti-apoptotic proteins in choriocarcinoma cells. Further, apomorphine caused depolarization of mitochondria, calcium overload, energy deprivation, and endoplasmic reticulum stress in JEG3 and JAR cells. We confirmed synergistic effects of apomorphine with paclitaxel, a traditional chemotherapeutic agent, and propose that apomorphine could be a potential therapeutic agent in choriocarcinoma and an important candidate for drug repositioning that could help overcome resistance to conventional chemotherapy.

scholarly journals Elucidation of the active compounds and molecular mechanisms of Smilacis Chinae Rhizoma for treatment of pelvic inflammatory disease based on network pharmacology and MMGBSA-docking

2020 ◽  
Author(s):  
Yunsen Zhang ◽  
Zikuang Zhao ◽  
Wenxiang Wang ◽  
Qi Li ◽  
Huimin Chen ◽  
...  
Keyword(s):  
Pelvic Inflammatory Disease ◽  
Signaling Pathway ◽  
Inflammatory Disease ◽  
Molecular Mechanisms ◽  
Binding Free Energy ◽  
Network Pharmacology ◽  
Therapeutic Effects ◽  
Active Ingredients ◽  
Active Compounds ◽  
Bidirectional Regulation

Abstract Background Smilacis Chinae Rhizoma (SCR) is widely used in the treatment of pelvic inflammatory disease (PID). However, its active ingredients and the mechanisms against PID remain elusive. This study aimed to clarify the active ingredients and explore their molecular mechanisms on PID. Method Network pharmacology and MMGBSA-docking exploited the active compounds and mechanisms against PID, as well as validating the binding mode of candidate targets.Results Network pharmacology revealed 32 active compounds and 718 compound-related targets mapped to 91 pathways which were clustered 7 genres (e.g., immunoregulation). C-T-P network and PPI analysis illustrated 17 PID-related targets, indicating that SCR may decrease inflammation, ameliorate fibrosis, and inhibit microorganisms via bidirectionally regulating IL-17 signaling pathway. Furthermore, active compounds were uncovered that bound to prostaglandin-endoperoxide synthase 2, matrix metalloprotein-9, lipocalin, signal transducer and activator of transcription 3, myeloperoxidase, and tumor necrosis factor. 19 active compounds (e.g., rutin (-66.43 kcal/mol), moracin M (-37.01 kcal/mol) and oxyresveratrol (-38.84 kcal/mol)) were found to show excellent binding free energy, demonstrating that H-bond, Pi electron cloud and electrostatic potential as the main binding ability to these targets. Conclusion Approach of network pharmacology and MMGBSA-docking revealed the active ingredients, such as rutin, moracin M, and oxyresveratrol, in SCR and dissected it exhibits the therapeutic effects (e.g., decrease inflammation, ameliorate fibrosis, and inhibit microorganisms) of PID by the bidirectional regulation of IL-17 signaling pathway.

scholarly journals Xiaoxuming Decoction: A Traditional Herbal Recipe for Stroke With Emerging Therapeutic Mechanisms

2021 ◽  
Vol 12 ◽  
Author(s):  
Qian Zhang ◽  
Yue Wang ◽  
Aiwen Chen ◽  
Xinwei Huang ◽  
Qianyu Dong ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Molecular Mechanisms ◽  
Neurovascular Unit ◽  
Alternative Therapy ◽  
Acute Stage ◽  
Therapeutic Effects ◽  
Active Compounds ◽  
Endovascular Thrombectomy ◽  
Therapeutic Mechanisms ◽  
New Perspective

Xiaoxuming decoction (XXMD) has been traditionally used to manage stroke though debates on its clinical efficacy were present in the history. Till nowadays, it is still one of the most commonly used herbal recipes for stroke. One of the reasons is that a decent proportion of ischemic stroke patients still have residue symptoms even after thrombolysis with rt-PA or endovascular thrombectomy. Numerous clinical studies have shown that XXMD is an effective alternative therapy not only at the acute stage, but also at the chronic sequelae stage of ischemic stroke. Modern techniques have isolated groups of compounds from XXMD which have shown therapeutic effects, such as dilating blood vessels, inhibiting thrombosis, suppressing oxidative stress, attenuating nitric oxide induced damage, protecting the blood brain barrier and the neurovascular unit. However, which of the active compounds is responsible for its therapeutic effects is still unknown. Emerging studies have screened and tested these active compounds aiming to find individual compounds that can be used as drugs to treat stroke. The present study summarized both clinical evidence of XXMD in managing stroke and experimental evidence on its molecular mechanisms that have been reported recently using advanced techniques. A new perspective has also been discussed with an aim to provide new targets that can be used for screening active compounds from XXMD.

scholarly journals Mechanism of Dark Plum In Treatment of Sjögren's Syndrome Based On Network Pharmacology And Molecular Docking​

2021 ◽  
Author(s):  
Zhongli Sun ◽  
Lilin Deng ◽  
Zhoujie Xu ◽  
Kun Yang ◽  
Penglong Yu
Keyword(s):  
Molecular Docking ◽  
Sjögren’S Syndrome ◽  
Molecular Mechanisms ◽  
Sjögren's Syndrome ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Network Pharmacology ◽  
Therapeutic Effects ◽  
Active Components ◽  
Sjögren‘S Syndrome

Abstract Background: Modern medicine has no cure for the xerostomia caused by the early onset of Sjögren's syndrome (SS).Dark plum is a common Chinese herbal medicine used to relieve xerostomia. However, the molecular mechanisms of the effects of dark plum are unknown. In this study, network pharmacology and molecular docking were used to investigate the mechanisms of action of dark plum on SS.Materials and method: The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) database was used to identify the active components and targets of dark plum, and the UniProt database was used to identify the genes encoding these targets. SS-related targets were also identified from the GeneCards and OMIM databases. By finding the intersection of the targets of the compounds and the targets of SS, the predicted targets of dark plum in the treatment of SS were obtained. Further investigation of the active compounds and their targets was carried out by constructing a network of "medicine-candidate compound-target-disease" using Cytoscape 3.7.2, the Protein-Protein Interaction(PPI) network using the STRING database and Cytoscape 3.7.2, and key targets were identified by Gene Ontology( GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis on R software. Finally, molecular docking was used to verify the affinity of the candidate compounds to the key targets.Results: Quercetin, beta-sitosterol, and kaempferol in dark plum interact with AKT1, IL-6, IL-1B, JUN, CASP3, and MAPK8. These results suggest that dark plum exerts its therapeutic effects on the peripheral gland injury of SS and its secondary cardiovascular disease and tumorigenesis through anti-inflammatory, anti-oxidant, and anti-tumor pathways.Conclusion: With network pharmacology, this study systematically identified the main active components, targets, and specific mechanisms of the therapeutic effects of dark plum on SS, providing both a theoretical basis and research direction for further investigations on dark plum.

A Network Pharmacology Analysis of the Systems-Perspective Anticancer Mechanisms of the Herbal Drug FDY2004 for Breast Cancer

2021 ◽  
Vol 16 (10) ◽  
pp. 1934578X2110491
Author(s):  
Ho-Sung Lee ◽  
In-Hee Lee ◽  
Kyungrae Kang ◽  
Sang-In Park ◽  
Tae-Wook Kwon ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Molecular Mechanisms ◽  
Enrichment Analysis ◽  
Network Pharmacology ◽  
Pathway Enrichment Analysis ◽  
Therapeutic Effects ◽  
Herbal Drugs ◽  
Apoptosis Pathway ◽  
Anticancer Properties ◽  
Systems Perspective

Breast cancer is a malignant tumor with high incidence, prevalence, and mortality rates in women. In recent years, herbal drugs have been assessed as anticancer therapy against breast cancer, owing to their promising therapeutic effects and reduced toxicity. However, their pharmacological mechanisms have not been fully explored at the systemic level. Here, we conducted a network pharmacology analysis of the systems-perspective molecular mechanisms of FDY2004, an anticancer herbal formula that consists of Moutan Radicis Cortex, Persicae Semen , and Rhei Radix et Rhizoma, against breast cancer. We determined that FDY2004 may contain 28 active compounds that exert pharmacological effects by targeting 113 breast cancer-related human genes/proteins. Based on the gene ontology terms, the FDY2004 targets were involved in modulating biological processes such as cell growth, cell proliferation, and apoptosis. Pathway enrichment analysis identified various breast cancer-associated pathways that may mediate the anticancer activity of FDY2004, including the PI3K-Akt, MAPK, TNF, HIF-1, focal adhesion, estrogen, ErbB, NF-kappa B, p53, and VEGF signaling pathways. Thus, our analysis offers novel insights into the anticancer properties of herbal drugs for breast cancer treatment from a systemic perspective.

The Pharmacological Rationales and Molecular Mechanisms of Ganoderma lucidum Polysaccharides for the Therapeutic Applications of Multiple Diseases

2021 ◽  
pp. 1-38
Author(s):  
Hua Luo ◽  
Dechao Tan ◽  
Bo Peng ◽  
Siyuan Zhang ◽  
Chi Teng Vong ◽  
...  
Keyword(s):  
Ganoderma Lucidum ◽  
Molecular Mechanisms ◽  
Chinese Herb ◽  
Network Pharmacology ◽  
Therapeutic Effects ◽  
Molecular Signaling ◽  
Transmission Mechanisms ◽  
Ganoderma Lucidum Polysaccharides ◽  
Anti Oxidant ◽  
Antibacterial And Antifungal

As a versatile Chinese herb, Ganoderma lucidum (Leyss. ex Fr.) Karst (G. lucidum) has been applied to treat multiple diseases in clinics and improve the quality of life of patients. Among all of its extracts, the main bioactive components are G. lucidum polysaccharides (GLPs), which possess many therapeutic effects, such as antitumor, immunoregulatory, anti-oxidant, antidiabetic, antibacterial, and antifungal effects and neuroprotection activities. This review briefly summarized the recent studies of the pharmacological rationales of GLPs and their underlying molecular signaling transmission mechanisms in treating diseases. Until now, the clear mechanisms of GLPs for treating diseases have not been reported. In this review, we used the keywords of “Ganoderma lucidum polysaccharides” and “tumor” to search in PubMed (years of 1992–2020), then screened and obtained 160 targets of antitumor activities in the literatures. The network pharmacology and mechanism framework were employed in this study as powerful approaches to systematically analyze the complicated potential antitumor mechanisms and targets of GLPs in cancer. We then found that there are 69 targets and 21 network pathways in “Pathways in cancer”. Besides, we summarized the effects of GLPs and the models and methods used in the research of GLPs. In conclusion, GLPs have been studied extensively, but more in-depth research is still needed to determine the exact mechanisms and pathways. Therefore, this review might provide new insights into the vital targets and pathways for researchers to study the pharmacological mechanisms of GLPs for the treatment of diseases.

scholarly journals In Silico and In Vivo Studies on the Mechanisms of Chinese Medicine Formula (Gegen Qinlian Decoction) in the Treatment of Ulcerative Colitis

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiaolu Liu ◽  
Yuling Fan ◽  
Lipeng Du ◽  
Zhigang Mei ◽  
Yang Fu
Keyword(s):  
Ulcerative Colitis ◽  
Molecular Docking ◽  
Chinese Medicine ◽  
In Silico ◽  
Molecular Mechanisms ◽  
Enrichment Analysis ◽  
Chronic Inflammatory Bowel Disease ◽  
Network Pharmacology ◽  
Therapeutic Effects ◽  
Tnf Α

Ulcerative colitis (UC) is a chronic inflammatory bowel disease, and Gegen Qinlian Decoction (GQD), a Chinese botanical formula, has exhibited beneficial efficacy against UC. However, the mechanisms underlying the effect of GQD still remain to be elucidated. In this study, network pharmacology approach and molecular docking in silico were applied to uncover the potential multicomponent synergetic effect and molecular mechanisms. The targets of ingredients in GQD were obtained from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and Bioinformatics Analysis Tool for Molecular mechANism of TCM (BATMAN-TCM) database, while the UC targets were retrieved from Genecards, therapeutic target database (TTD) and Online Mendelian Inheritance in Man (OMIM) database. The topological parameters of Protein-Protein Interaction (PPI) data were used to screen the hub targets in the network. The possible mechanisms were investigated with gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Molecular docking was used to verify the binding affinity between the active compounds and hub targets. Network pharmacology analysis successfully identified 77 candidate compounds and 56 potential targets. The targets were further mapped to 20 related pathways to construct a compound-target-pathway network and an integrated network of GQD treating UC. Among these pathways, PI3K-AKT, HIF-1, VEGF, Ras, and TNF signaling pathways may exert important effects in the treatment of UC via inflammation suppression and anti-carcinogenesis. In the animal experiment, treatment with GQD and sulfasalazine (SASP) both ameliorated inflammation in UC. The proinflammatory cytokines (TNF-α, IL-1β, and IL-6) induced by UC were significantly decreased by GQD and SASP. Moreover, the protein expression of EGFR, PI3K, and phosphorylation of AKT were reduced after GQD and SASP treatment, and there was no significance between the GQD group and SASP group. Our study systematically dissected the molecular mechanisms of GQD on the treatment of UC using network pharmacology, as well as uncovered the therapeutic effects of GQD against UC through ameliorating inflammation via downregulating EGFR/PI3K/AKT signaling pathway and the pro-inflammatory cytokines such as TNF-α, IL-1β and IL-6.

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