Study on pharmacological mechanism of traditional Chinese medicine in intervention of cardiomyocyte apoptosis and targets prediction based on literature mining

Abstract Background: Jianghuang (JH) is a popular ingredient in blood-regulating traditional Chinese Medicine (TCM) that could be effective for the treatment of various diseases. We demonstrate the compatibility laws and system pharmacological mechanisms of the key formula containing JH by leveraging data mining of bioinformatics databases.Material/Methods: The compatibility laws of blood-regulating formulae containing JH from the Chinese Traditional Medicine Formula Dictionary were analyzed using a generalized rule induction (GRI) algorithm implemented. The putative target gene and miRNA were retrieved via a combination of the Arrowsmith knowledge discovery tool and FunRich 3.1.3. System pharmacological mechanisms are traced by their protein-protein interaction (PPI) network, and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was conducted using Uniprot, the Human Protein Atlas (HPA), STRING 11.0, and KOBAS 3.0.Results: We found that the JH-CX-DG formula (Ligusticum chuanxiong-Angelica sinensis) could represent a key formula containing JH in blood-regulating TCM formulae. The JH-CX-DG formula was observed to directly target AKT, TLR4, caspase-3, PI3K, mTOR, p38 MAPK, VEGF, iNOS, Nrf2, BDNF, NF-κB, Bcl-2, and Bax 13 targets and regulate targets through 13 miRNA. The PPI network and KEGG pathway enrichment analysis showed that the JH-CX-DG formula possess potential pharmacological effects including anti-inflammatory, improving microcirculation, and anti-tumor through the regulation of multiple pathways including PI3K/Akt, MAPK, Toll-like receptor, T cell receptor, EGFR, VEGFR, Apoptosis, HIF-1 (p < 0.05).Conclusion: The JH-CX-DG formula can exert beneficial pharmacological effects through multi-target and multi-pathway interactions. It can be effectively administered for the treatment of inflammatory diseases, microcirculation disorders, cardiovascular disease, and cancer. We found a new effective drug formula through analyzing the compatibility law and systemic pharmacological mechanism of JH. Our study provides a theoretical basis and directions for subsequent research on the JH-CX-DG formula.

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Revealing the potential pharmacological mechanism of traditional Chinese medicine by integrating metabolite profiling of Q-marker and network pharmacology, prim-O-glucosylcimifugin as an example

New Journal of Chemistry ◽

10.1039/d1nj02209a ◽

2021 ◽

Author(s):

Fengxiang Zhang ◽

Yu-Lin-Lan Yuan ◽

Shuang-shuang Cui ◽

Guanhua Wang ◽

Rui-man Li

Keyword(s):

Quality Control ◽

Chinese Medicine ◽

Traditional Chinese Medicine ◽

Metabolite Profiling ◽

Network Pharmacology ◽

Clinical Effects ◽

Pharmacological Mechanism

Along with the definite clinical effects, traditional Chinese medicine (TCM) increasingly gains worldwide attention. Quality control marker (Q-marker) is always used to confirm the primary effects of herbs or TCM....

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GANODERMA LUCIDUM: A TRADITIONAL CHINESE MEDICINE USED FOR CURING TUMORS

International Journal of Pharmacy and Pharmaceutical Sciences ◽

10.22159/ijpps.2021v13i3.40614 ◽

2021 ◽

pp. 1-13

Author(s):

ARUN KUMAR

Keyword(s):

Chinese Medicine ◽

Traditional Chinese Medicine ◽

Ganoderma Lucidum ◽

Herbal Remedy ◽

Chemical Constituents ◽

Deciduous Trees ◽

Pharmacological Mechanism ◽

Coffee Powder

Ganoderma lucidum is generally called “Lingzhi or Reishi”, and also be a Traditional Chinese medicine utilized in over 2000 y for their better therapeutic activity like antitumor, antiallergenic, antiviral, hepatoprotective, antioxidant, hypotensive, immunomodulator, hypoglycemic, anti-inflammatory, antithrombotic, antibacterial and many other health benefits. Ganoderma lucidum is one of the oldest herbal remedy found and grow in wide variety parts on deciduous trees (dead/dying tree) specifically in oak, pyrus, maple, elm, willow, sweetgum, magnolia, locust, acer, betula, castanea, coryolus, fagus, populus, plums and other plants species. It also be contains 400 major bioactive chemical constituents include polysaccharides, triterpenoids, polysaccharide-peptide complex, β-glucans, lectins, natural germanium (Ge), adenosine, phenols, steroids, amino acids, lignin, vitamins, nucleotides or nucleosides possesses specific curative properties and formed a wide variety of viable products from Ganoderma fruiting bodies, mycelia, spores i.e. coffee, powder, dietary enhancements, tea, spore items, drinks, syrups, toothpastes, cleansers or creams. Many in vitro or in vivo analyses with regards Ganoderma lucidum evidenced their antitumor activity but some conducted clinical studies are questionable and remains undefined for their antitumor effect. Though, we reviewed and summarized in this article about treatment and various pharmacological mechanism against tumor with respect to extract (polysaccharide and triterpenoid) of Ganoderma lucidum.

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In silico identification of natural products from Traditional Chinese Medicine for cancer immunotherapy

Scientific Reports ◽

10.1038/s41598-021-82857-2 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Chuipu Cai ◽

Qihui Wu ◽

Honghai Hong ◽

Liying He ◽

Zhihong Liu ◽

...

Keyword(s):

Natural Products ◽

Chinese Medicine ◽

Traditional Chinese Medicine ◽

Cancer Immunotherapy ◽

Functional Enrichment ◽

Literature Mining ◽

Systems Pharmacology ◽

Scutellaria Baicalensis Georgi

AbstractAdvances in immunotherapy have revolutionized treatments in many types of cancer. Traditional Chinese Medicine (TCM), which has a long history of clinical adjuvant application against cancer, is emerging as an important medical resource for developing innovative cancer treatments, including immunotherapy. In this study, we developed a quantitative and systems pharmacology-based framework to identify TCM-derived natural products for cancer immunotherapy. Specifically, we integrated 381 cancer immune response-related genes and a compound-target interaction network connecting 3273 proteins and 766 natural products from 66 cancer-related herbs based on literature-mining. Via systems pharmacology-based prediction, we uncovered 182 TCM-derived natural products having potential anti-tumor immune responses effect. Importantly, 32 of the 49 most promising natural products (success rate = 65.31%) are validated by multiple evidence, including published experimental data from clinical studies, in vitro and in vivo assays. We further identified the mechanism-of-action of TCM in cancer immunotherapy using network-based functional enrichment analysis. We showcased that three typical natural products (baicalin, wogonin, and oroxylin A) in Huangqin (Scutellaria baicalensis Georgi) potentially overcome resistance of known oncology agents by regulating tumor immunosuppressive microenvironments. In summary, this study offers a novel and effective systems pharmacology infrastructure for potential cancer immunotherapeutic development by exploiting the medical wealth of natural products in TCM.

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A Multi-Scale Bioinformatics Study on Novel Mechanism of Xintong Granule for Treating Coronary Heart Disease by Network Pharmacology and Molecular Docking Verification

10.21203/rs.3.rs-116130/v1 ◽

2020 ◽

Author(s):

Zhihong Huang ◽

Siyu Guo ◽

Changgeng Fu ◽

Wei Zhou ◽

Jingyuan Zhang ◽

...

Keyword(s):

Coronary Heart Disease ◽

Heart Disease ◽

Molecular Docking ◽

Chinese Medicine ◽

Traditional Chinese Medicine ◽

Signaling Pathway ◽

Chinese Herbs ◽

Network Pharmacology ◽

Pharmacological Mechanism ◽

Vascular Regulation

Abstract Background: Xintong Granule (XTG) is a Chinese patent medicine composed of 13 Chinese herbs, which is widely used in the treatment of coronary heart disease (CHD). However, there are few studies on it, and its potential pharmacological mechanism needs to be further elucidated.Methods: In this study, network pharmacology was employed to construct the drug-compounds-targets-pathways molecular regulatory network of the treatment of CHD to explore the effective compounds of XTG and its underlying pharmacological mechanism. First, we established the related ingredients and potential targets of these ingredients databases by Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) and A Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine (BATMAN-TCM). Next, the CHD targets were obtained in DigSee, OMIM, DisGeNET, TTD, GeneCards and GenCLiP3 database. Then, protein-protein interaction (PPI) analysis, GO and KEGG pathway enrichment analysis were carried out and the core targets were filtered by topology. Moreover, molecular docking was performed to assess the binding potential of hub targets and key compounds.Results: The result reflected that 178 components of XTG and 669 putative therapeutic targets were screened out. After a systematic and comprehensive analysis, we identified 9 hub targets (TNF, MAPK1, STAT3, IL6, AKT1, INS, EGFR, EGF, TP53) primarily participated in the comprehensive therapeutic effect related to blood circulation, vascular regulation, cell membrane region, compound binding, receptor activity, signal transduction, AGE-RAGE signaling pathway in diabetic complications, JAK-STAT signaling pathway, PI3K-AKT signaling pathway and MAPK signaling pathway.Conclusion: The results of this study tentatively clarified the potential targets and signaling pathways of XTG against CHD, which may benefit to the development of clinical experimental research and application.

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Traditional Chinese medicine in treating IgA nephropathy: from basic science to clinical research

Journal of Translational Internal Medicine ◽

10.2478/jtim-2021-0021 ◽

2021 ◽

Vol 9 (3) ◽

pp. 161-167

Author(s):

Xin-hui Wang ◽

Rui Lang ◽

Ying Liang ◽

Qin Zeng ◽

Nan Chen ◽

...

Keyword(s):

Chinese Medicine ◽

Traditional Chinese Medicine ◽

Iga Nephropathy ◽

Basic Science ◽

Mesangial Cells ◽

Herbal Medicines ◽

Clinical Effects ◽

Glomerular Mesangial Cells ◽

High Quality Research ◽

Pharmacological Mechanism

Abstract IgA nephropathy (IgAN) is a major cause of chronic kidney disease (CKD) and end-stage renal disease worldwide. Currently, clinical interventions for IgAN are limited, and many patients seek out alternative therapies such as traditional Chinese medicine (TCM). In the last several years, TCM has accumulated ample application experiences and achieved favorable clinical effects. This article summarizes high-quality research from basic science to clinical applications aimed to provide more evidence-based medicine proof for the clinical treatment of IgAN. In summary, qi and yin deficiency accounted for the largest proportion in IgAN patients, and the treatment of IgAN should be based on supplementing qi and nourishing yin. Further, for patients with severe IgAN, the treatment combination of Chinese and Western medicines is better than pure Chinese medicine or hormone therapy. In addition, the pharmacological mechanism of Chinese herbal medicines is mostly based on restoring the immune function, relieving the inflammation damage, and inhibiting proliferation of the glomerular mesangial cells.

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Network Pharmacology and Molecular Docking Combined to Analyze the Molecular and Pharmacological Mechanism of Pinellia ternata in the Treatment of Hypertension

Current Issues in Molecular Biology ◽

10.3390/cimb43010006 ◽

2021 ◽

Vol 43 (1) ◽

pp. 65-78

Author(s):

Zhaowei Zhai ◽

Xinru Tao ◽

Mohammad Murtaza Alami ◽

Shaohua Shu ◽

Xuekui Wang

Keyword(s):

Molecular Docking ◽

Chinese Medicine ◽

Traditional Chinese Medicine ◽

Western Medicine ◽

Network Pharmacology ◽

Ppi Network ◽

Active Components ◽

Pharmacological Mechanism ◽

Effective Components ◽

Treatment Of Hypertension

Hypertension is a cardiovascular disease that causes great harm to health and life, affecting the function of important organs and accompanied by a variety of secondary diseases, which need to be treated with drugs for a long time. P. ternata alone or combination with western medicine has played an important role in traditional Chinese medicine. Although P. ternata is used clinically to treat hypertension, its functional molecular mechanism and pharmacological mechanism have not been elucidated. Therefore, in this study, the potentially effective components, and targets of P. ternata in the treatment of hypertension were screened by the method of network pharmacology, and the mechanism of P. ternata in the treatment of hypertension was analyzed by constructing a component-target relationship network, PPI interaction network, targets’ function analysis, and molecular docking. In the study, 12 potentially effective components and 88 targets were screened, and 3 potential protein modules were found and analyzed after constructing a PPI network using targets. In addition, 10 targets were selected as core targets of the PPI network. After that, the targets were analyzed by Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Finally, the molecular docking method is used to study the interaction between the targets and the active components. The above evidence shows that the mechanism of P. ternata in the treatment of hypertension is complicated, as it acts in many ways, mainly by affecting nerve signal transmission, cell proliferation, and apoptosis, calcium channels, and so on. The binding between targets and active components mainly depends on Pi bonds and hydrogen bonds. Using the method of network pharmacology and molecular docking to analyze the mechanism of P. ternata in the treatment of hypertension will help to provide a better scientific basis for the combined use of traditional Chinese medicine and western medicine, and will better help to improve the quality of P. ternata and point out its direction.

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DCABM-TCM, a Database of Constituents Absorbed into Blood and Metabolites of Traditional Chinese Medicine

10.21203/rs.3.rs-409645/v1 ◽

2021 ◽

Author(s):

Xinyue Liu ◽

Jinying Liu ◽

Feng Xu ◽

Runa Li ◽

Lin Xing ◽

...

Keyword(s):

Chinese Medicine ◽

Traditional Chinese Medicine ◽

Drug Development ◽

Molecular Mechanism ◽

Network Pharmacology ◽

Literature Mining ◽

Pharmacological Effects ◽

Widespread Application ◽

Blood Constituents ◽

Modern Drug

Abstract Traditional Chinese Medicine (TCM) not only maintains the health of peoples in Asia but also provides a great resource of active natural products for modern drug development. However, owing to its diverse constituents and the complex interactions with the human body, it is still challenging to clarify its effective constituents and molecular mechanism. This greatly hinders its widespread application worldwide and TCM-based modern drug development. The vast majority of constituents in TCM can produce pharmacological effects only after they are absorbed into bloodstream. Compared with ordinary constituents generally detected in vitro, these that are verified to reach the bloodstream, including original constituents absorbed into blood and metabolites of original constituents produced by the gastrointestinal tract, intestinal microflora, and liver, are more likely to be really effective ones responsible for the pharmacological effects. Here we developed DCABM-TCM (a Database of Constituents Absorbed into Blood and Metabolites of TCM), the first database systematically collecting blood constituents of TCM prescriptions and herbs, including prototypes and metabolites experimentally-detected in blood, together with the corresponding detailed detection conditions by manual literature mining. Currently DCABM-TCM has collected 4206 blood constituents of 192 prescriptions and 194 herbs, and also integrated various related annotations including physicochemical properties, ADMET properties, and associated targets, functional terms, pathways, and diseases etc. Furthermore, DCABM-TCM supported two analysis functions, the network pharmacology analysis for TCM molecular mechanism elucidation and the target/pathway/disease-based screening of candidate blood constituents, herbs or prescriptions for TCM-based drug discovery. DCABM-TCM is freely assessable by http://bionet.ncpsb.org.cn/dcabm-tcm/ and is browsable and searchable for each of 6 kinds of entities, including prescriptions, herbs, blood constituents, targets, pathways, and diseases. DCABM-TCM will contribute to not only the elucidation of effective constituents and molecular mechanism of TCMs but also the discovery of TCM-derived drug-like compounds which are both bioactive and bioavailable, the feature investigation of absorbable natural compounds, and the quality control of herbs.

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Deciphering potential pharmacological mechanism of Sha-Shen-Mai-Dong decoction on primary Sjogren’s syndrome

BMC Complementary Medicine and Therapies ◽

10.1186/s12906-021-03257-7 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Yuepeng Jiang ◽

Xiaoxuan Zhao ◽

Jie Yu ◽

Qiao Wang ◽

Chengping Wen ◽

...

Keyword(s):

Molecular Docking ◽

Chinese Medicine ◽

Traditional Chinese Medicine ◽

Sjogren's Syndrome ◽

Primary Sjögren’S Syndrome ◽

Active Components ◽

Primary Sjogren’S Syndrome ◽

Primary Sjögren's Syndrome ◽

Pharmacological Mechanism ◽

Kegg Analysis

Abstract Background Sha-Shen-Mai-Dong decoction (SSMD) is a classical prescription widely used in primary Sjogren’s Syndrome (pSS) therapy. This study aims to explore the potential pharmacological mechanism of SSMD on pSS. Methods Active components of SSMD were obtained from Traditional Chinese Medicine Integrative Database and Traditional Chinese Medicine Systems Pharmacology databases and targets of SSMD were predicted by Pharmmapper and STITCH database. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were carried out to explore the function characteristics of SSMD. The expression matrix of microarray of pSS was obtained from Gene Expression Omnibus and we obtained 162 differentially expressed genes (DEGs). Protein-protein interaction (PPI) networks were constructed to identify the hub targets. Principal component analysis (PCA) and molecular docking were conducted to further elucidate the possibility of SSMD for pSS. Results SSMD contained a total of 1056 active components, corresponding to 88 targets, among which peripheral myelin protein 2(PMP2), androgen receptor (AR) and glutamic acid decarboxylase 1(GAD1) are associated with multiple active components in SSMD and may be the core targets. Moreover, these targets were closely related to tissue pathological injury in SS, such as lacrimal gland, salivary gland and nervous system injury. GO and KEGG analysis showed that 88 targets enriched in REDOX process, transcriptional regulation and negative regulation of apoptosis process. Besides, SSMD may influence the cell proliferation, gene transcription through regulating Ras and cAMP-related signaling pathways. In addition, SSMD may show effects on immune regulation, such as macrophage differentiation, Toll-like receptor 4 signaling pathway and T-helper 1 in SS. Moreover, PPI network suggested that FN1, MMP-9 may be the hub targets in SSMD. Result of PCA and molecular docking analysis further determined the feasibility of SSMD in treating pSS. Conclusion SSMD can regulate multiple biological processes by virtue of its multiple active components, thus showing prominent advantage in the treatment of pSS. The discovery of active ingredients and targets in SSMD provides valuable resources for drug research and development for pSS.

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Systematic Understanding of the Mechanism of Baicalin against Ischemic Stroke through a Network Pharmacology Approach

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2018/2582843 ◽

2018 ◽

Vol 2018 ◽

pp. 1-11 ◽

Cited By ~ 5

Author(s):

Tian Xu ◽

Chongyang Ma ◽

Shuning Fan ◽

Nang Deng ◽

Yajun Lian ◽

...

Keyword(s):

Ischemic Stroke ◽

Chinese Medicine ◽

Protein Kinase ◽

Traditional Chinese Medicine ◽

Signaling Pathways ◽

Mitogen Activated Protein Kinase ◽

System Level ◽

Network Pharmacology ◽

Literature Mining ◽

Ppi Networks

Ischemic stroke is accompanied by high mortality and morbidity rates. At present, there is no effective clinical treatment. Alternatively, traditional Chinese medicine has been widely used in China and Japan for the treatment of ischemic stroke. Baicalin is a flavonoid extracted from Scutellaria baicalensis that has been shown to be effective against ischemic stroke; however, its mechanism has not been fully elucidated. Based on network pharmacology, we explored the potential mechanism of baicalin on a system level. After obtaining baicalin structural information from the PubChem database, an approach combined with literature mining and PharmMapper prediction was used to uncover baicalin targets. Ischemic stroke-related targets were gathered with the help of DrugBank, Online Mendelian Inheritance in Man (OMIM), Genetic Association Database (GAD), and Therapeutic Target Database (TTD). Protein-protein interaction (PPI) networks were constructed through the Cytoscape plugin BisoGenet and analyzed by topological methods. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were carried out via the Database for Annotation, Visualization, and Integrated Discovery (DAVID) server. We obtained a total of 386 potential targets and 5 signaling pathways, including mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT), hypoxia-inducible factor-1 (HIF-1), nuclear factor kappa B (NF-κB), and forkhead box (FOXO) signaling pathways. GO analysis showed that these targets were associated with antiapoptosis, antioxidative stress, anti-inflammation, and other physiopathological processes that are involved in anti-ischemic stroke effects. In summary, the mechanism of baicalin against ischemic stroke involved multiple targets and signaling pathways. Our study provides a network pharmacology framework for future research on traditional Chinese medicine.

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