• Herbal Formula Science
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• v.32 no.1
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• pp.11-28
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• 2024

Objectives : GunRyeong-Tang(GRT) is a traditional herbal prescription that combines Oryeongsan and Sagunja-tang. This study employed network analysis methods on the components of GRT and target genes related to diabetes complications to predict the improvement effects of GRT on diabetes complications. Methods : The collection of active compounds of GRT and related target genes involved the utilization of public databases and the PubChem database. We selected diabetes complication-related genes using GeneCards and confirmed their correlation through comparative analysis with the target genes of GRT. We constructed a network using Cytoscape 3.9.1 and conducted topological analysis. To predict the mechanism, we performed functional enrichment analysis based on Gene Ontology (GO) biological processes and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Results : Through network analysis, 234 active compounds and 1361 related genes were collected from GRT. A total of 9,136 genes related to diabetes complications were collected, and 1,039 target genes overlapping with the components of GRT were identified. The core genes of this network were TP53, INS, AKT1, ALB, and EGFR. In addition, GRT significantly reduced the H9c2 cell size and the expression of myocardial hypertrophy biomarkers (ANP, BNP), which were increased by high glucose (HG). Conclusions : Through this study, we were able to predict the activity and mechanism of action of GRT on diabetes and diabetic complications, and confirmed the potential of GRT as a treatment for diabetes complications through the effect of GRT on improving myocardial hypertrophy for diabetic cardiomyopathy.

• Herbal Formula Science
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• v.32 no.3
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• pp.247-261
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• 2024

Objectives : Zuojin Pill, recognized as an effective herbal remedy, has undergone investigation for its potential in alleviating symptoms like indigestion, vomiting, and abdominal distension. The purpose of this study was to investigate the mechanism of digestive function activation through network pharmacology, particularly focused on improving functional dyspepsia. Methods : The two components, Coptidis Rhizoma and Evodiae Fructus, constituting Zuojin Pill were analyzed based on broad information on chemical and pharmacological properties, confirming 40 active compounds and 115 digestive-related molecular targets. Concentration analysis revealed impacts on various pathways related to digestive functions. Results : According to network pharmacological analysis of Zuojin Pill, quercetin and beta-sitosterol were exhibited relatively numerous targets, suggesting their potential significance in the therapeutic activity of Zuojin Pill and by a Protein-Protein Interaction (PPI) network, JUN, RELA, MAPK1, HSP90AA1, TP53, TNF, AKT1, IL6, MAPK14, ESR1, FOS, MYC were identified. Also, berberine exhibited the highest contribution index (92.58%), indicating that this compound may be a major contributor to the digestive activity of Zuojin Pill. Additionally, functional interaction analysis by GeneMANIA indicated that targets of Zuojin Pill could functionally interact through various mechanisms, implying similarities in pharmacological roles. Conclusions : These findings contribute valuable insights into the digestive function activation mechanism and highlight the therapeutic potential of Zuojin Pill in improving functional dyspepsia.

• Herbal Formula Science
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• v.29 no.1
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• pp.19-31
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• 2021

Objectives : The root of Salvia miltiorrhiza, known as 'Dansam (DS, 丹參)', is used for and treating cardiovascular diseases based on its efficacy of promoting blood circulation and breaking through a blood stasis. In this study, we would like to see if DS could be effectively used for stroke from the perspective of network pharmacology. Methods : The analysis was conducted using Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) database to derive the main active compounds of DS and identify the mechanism of each compound acting on the human body. The networks between compounds, target protein and disease were expressed through Cytoscape. Protein-protein interaction (PPI) analysis was performed using STRING database. Results : Fifty two active compounds of DS were identified by screening the ingredients of DS through TCMSP. Based on the networks of these compounds with target protein and disease, it can be said that DS might be effective for preventing and treating stroke. PPI result showed that adrenergic receptor has many interactions among proteins, indicating its significance in stroke pathway. Conclusion : In this study, we derived target proteins and target diseases of DS that could be used in study of stroke. However, since it is uncertain if these targets can be controlled by DS extracts or not, we would like to confirm the results with further animal experiments.

• Herbal Formula Science
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• v.31 no.3
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• pp.145-156
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• 2023

Objectives : This study aimed to select candidate herbal medicines to be used in preclinical studies of cerebral infarction using the network pharmacology research method. Methods : Oral bioavailability (OB), drug likeness (DL), Caco-2, and blood-brain barrier (BBB) permeability were employed in this study's network pharmacology analysis method to choose compounds with potential efficacy. The following formulas were utilized for the values of each variable used in this study: OB ≥ 20%, DL ≥ 0.18, Caco-2 ≥ 0, and BBB ≥ -0.3. The relationships between target proteins and diseases that are assumed to be involved in the chosen bioavailable chemicals were built in a network manner using the aforementioned factors, and proteins thought to play a significant role were identified. Results : Sudan III was obtained as a result of selecting compounds related to ischemic stroke in consideration of pharmacokinetic characteristics such as digestion and absorption and practicality using the TCMSP database. Medicinal herbs Gardeniae Fructus (GF) contains sudan III, and it was confirmed that compounds in GF were highly related to brain diseases, and the mechanism involved through the KEGG pathway was confirmed. GF, which has sudan III related to ischemic stroke and is also involved in other neurological diseases, is expected to be used for ischemic stroke treatment. Conclusions : GF has been predicted to have potential for ischemic stroke treatment, and can be used for future preclinical studies.

• The Korea Journal of Herbology
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• v.39 no.3
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• pp.37-47
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• 2024

Objectives : Because predicting the potential efficacy and mechanisms of Korean medicines is challenging due to their high complexity, employing an approach based on network pharmacology could be effective. In this study, network pharmacological analysis was utilized to anticipate the effects of YunPye-Hwan (YPH) in treating Chronic obstructive pulmonary disease (COPD). Methods : Compounds and their related target genes of YPH were gathered from the TCMSP and PubChem databases. These target genes of YPH were subsequently compared with gene sets associated with COPD to assess correlation. Next, core genes were identified through a two-step screening process, and finally, functional enrichment analysis of these core genes was conducted using both Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathways. Results : A total of 15 compounds and 437 target genes were gathered, resulting in a network comprising 473 nodes and 14,137 edges. Among them, 276 genes overlapped with gene sets associated with COPD, indicating a significant correlation between YPH and COPD. Functional enrichment analysis of the 18 core genes revealed biological processes and pathways such as "miRNA Transcription," "Nucleic Acid-Templated Transcription," "DNA-binding Transcription Factor Activity," "MAPK signaling pathway," and "TNF signaling pathway" were implicated. Conclusion : YPH exhibited significant relevance to COPD by modulating cell proliferation, differentiation, inflammation, and cell death pathways. This study could serve as a foundational framework for further research investigating the potential use of YPH in the treatment of COPD.

• Herbal Formula Science
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• v.31 no.4
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• pp.245-252
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• 2023

Objectives : The purpose of this study was to explore the compounds, targets and related diseases of garlic by the approaches of network pharmacology and bioinformatics in traditional chinese medicine. Methods : We investigated components and their target molecules of garlic using SymMap and TCMSP and they were compared with analysis platform. Results : 56 potential compounds were identified in garlic, 26 of which contained target information, and it was found that these 26 compounds and 154 targets interact with each other through a combination of 243 compounds. In addition, Apigenin was linked to the most targeted gene (78) in 26 compounds, followed by Kaempferol (61 genes), Nicotic Acid (14 genes), Geraniol (11 genes), Eee (10 genes), and Sobrol A (9 genes). Among 56 potential compounds, three compounds (Kaempferol, Dipterocarpol, and N-Methyl cytisine) corresponded to the active compound by screening criterion Absorption, Distribution, Metabolism, Excretion (ADME). In addition, 12 compounds in 56 potential compounds were associated with gastrointestinal (GI) motility disorder. Among them, Kaempferol was a compound that met the ADME parameters and the rest were potential compounds that did not meet. Also, Kaempferol was closely related to GI motility disorder, indicating that this Kaempferol could be a candidate for potential medical efficacy. Conclusions : It shows the relationship between the compound of garlic, an herbal supplement, and the biological process associated with GI motility disorder. These results are thought to help develop strategies for treating GI motility disorders.

• Journal of Physiology & Pathology in Korean Medicine
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• v.30 no.6
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• pp.385-396
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• 2016

It is a fact that the existing pharmacological research method is difficult to explain the effect and mechanism of action of herbal formula of Korean medicine. We are now very pleased with the development of modern science and the development of a methodology for studying herbal formula characterized by network targets and multi-component therapeutics over the human body. In this review, systems pharmacology or network pharmacology is demonstrated how these are applied to explain the effectiveness of herbal medicine. The post-genomic era provides a unique opportunity for the two fields to understand and benefit from each other. In particular, recent research trends, research methodology, useful databases and results of research on herbal formula are introduced. China already has a policy of scientific development of traditional chinese medicine (TCM) and the development of Chinese medicine industry with a focus on herbal formula research at national level, and in Korea, it is urgent to support and nurture the methodology appropriate to the characteristics of the herbal formula in order to study the safety and efficacy of Korean medicine.

• Journal of Physiology & Pathology in Korean Medicine
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• v.35 no.5
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• pp.125-131
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• 2021

The scientific understanding of Korean medicine theory remains largely unknown, since there is a lack of proper methods to investigate its complex and unique characteristics. Here, we introduce a drug-centered approach, a novel method to investigate Korean medicine theory by analyzing the mechanisms of herbal medicines. This method can be effectively conducted by employing network pharmacology that can analyze the systems-level mechanisms of herbal medicines on a large scale. Firstly, we introduce the method of network pharmacology that are applied to analyze the mechanisms of herbal medicines in a step-by-step manner. Then, we show how the drug-centered approach employing network pharmacology can be applied to investigate Korean medicine theory by describing studies that identify the biological correlates of the cold-hot nature of herbs, spleen qi deficiency syndrome, or Sasang constitution. Finally, we discuss the limitations and future directions of the proposed approach in two aspects: The methods of network pharmacology for a drug-centered approach and the process of inferring Korean medicine theory through it. We believe that a drug-centered approach employing network pharmacology will provide an advanced scientific understanding of Korean medicine theory and contribute to its development by generating biologically plausible hypothesis.

• Herbal Formula Science
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• v.30 no.4
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• pp.293-304
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• 2022

Objectives : Sagunja-Tang is a famous prescription used in Korean medicine for the purpose of promoting vital energy, and there are few studies using Sagunja-Tang on cerebrovascular diseases yet. As previous studies confirmed that Sagunja-tang is highly likely to be used effectively for stroke, this study was intended to predict the mechanism through which Sagunja-tang would act effectively on stroke. Methods : In this study, a network pharmacology analysis method was used, and oral bioavailability (OB), drug likeness (DL), Caco-2 and BBB permeability were utilized to select compounds with potential activity. For the values of each variable used in this study, OB ≥ 30%, DL ≥ 0.18, Caco-2 ≥ 0, and BBB ≥ 0.3 were applied. Using the above variables, the relations between target genes and diseases that are presumed to be involved in the selected bioavailable compounds were constructed in a network format, and proteins thought to play a major role were identified. Results : Among the compounds included in Sagunja-Tang, 26 bioavailable compounds were selected and it was confirmed that these compounds can be effectively used in cerebrovascular diseases such as Alzheimer's disease and stroke. These compounds are considered to act on proteins related in cell death and growth. The most important mechanism of action was predicted to be apoptosis, and the protein that is thought to play the most key action in this mechanism was caspase-3. Conclusions : In our future study, Sagunja-Tang will be used in an ischemic stroke mouse model, and the mechanism of action will be explored focusing on apoptosis and cell proliferation.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.36 no.1
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• pp.50-63
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• 2023

Objectives : This study used a network pharmacology approach to explore the active compounds and therapeutic mechanisms of Yijin-tang on Meniere's disease. Methods : The active compounds of Yijin-tang were screened via the TCMSP database and their target proteins were screened via the STITCH database. The GeneCard was used to establish the Meniere's disease-related genes. The intersection targets were obtained through Venny 2.1.0. The related protein interaction network was constructed with the STRING database, and topology analysis was performed through CytoNCA. GO biological function analysis and KEGG enrichment analysis for core targets were performed through the ClueGO. Results : Network analysis identified 126 compounds in five herbal medicines of Yijin-tang. Among them, 15 compounds(naringenin, beta-sitosterol, stigmasterol, baicalein, baicalin, calycosin, dihydrocapsaicin, formononetin, glabridin, isorhamnetin, kaempferol, mairin, quercetin, sitosterol, nobiletin) were the key chemicals. The target proteins were 119, and 7 proteins(TNF, CASP9, PARP1, CCL2, CFTR, NOS2, NOS1) were linked to Meniere's disease-related genes. Core genes in this network were TNF, CASP9, and NOS2. GO/KEGG pathway analysis results indicate that these targets are primarily involved in regulating biological processes, such as excitotoxicity, oxidative stress, and apoptosis. Conclusion : Pharmacological network analysis can help to explain the applicability of Yijin-tang on Meniere's disease.