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Exploring the Pharmacological Mechanism of the Herb Pair "HuangLian-GanJiang" against Colorectal Cancer Based on Network Pharmacology.

ABSTRACT: Since the herb pair Huang Lian-Gan Jiang (HL-GJ) was put forward as conventional compatibility for cold-heat regulation in the middle energizer in the theory of Traditional Chinese Medicine (TCM), their therapeutic effects were observed on the prevention and treatment of intestinal inflammation and tumors including colorectal cancer (CRC). However, the active compounds, crucial targets, and related pathways of HL-GJ against CRC remained unclear. The purpose of this research was to establish a comprehensive and systemic approach that could identify the active compounds, excavate crucial targets, and reveal anti-CRC mechanisms of HL-GJ against CRC based on network pharmacology. We used methods including chemical compound screening based on absorption, distribution, metabolism, and excretion (ADME), compound target prediction, CRC target collection, network construction and analysis, Gene Ontology (GO), and pathway analysis. In this study, eight main active compounds of HL-GJ were identified, including Gingerenone C, Isogingerenone B, 5,8-dihydroxy-2-(2-phenylethyl) Chromone, 2,3,4-trihydroxy-benzenepropanoic acid, 3,4-dihydroxyphenylethyl Alcohol Glucoside, 3-carboxy-4-hydroxy-phenoxy Glucoside, Moupinamide, and Obaculactone. HRAS, KRAS, PIK3CA, PDE5A, PPARG, TGFBR1, and TGFBR2 were identified as crucial targets of HL-GJ against CRC. There were mainly 500 biological processes and 70 molecular functions regulated during HL-GJ against CRC (P < 0.001). There were mainly 162 signaling pathways contributing to therapeutic effects (P < 0.001), the top 10 of which included DAP12 signaling, signaling by PDGF, signaling by EGFR, NGF signaling via TRKA from the plasma membrane, signaling by NGF, downstream signal transduction, DAP12 interactions, signaling by VEGF, signaling by FGFR3, and signaling by FGFR4. The study established a comprehensive and systematic paradigm to understand the pharmacological mechanisms of multiherb compatibility such as an herb pair, which might accelerate the development and modernization of TCM.

SUBMITTER: Gong B

PROVIDER: S-EPMC6906823 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Exploring the Pharmacological Mechanism of the Herb Pair "HuangLian-GanJiang" against Colorectal Cancer Based on Network Pharmacology.

Gong Benjiao B Kao Yanlei Y Zhang Chenglin C Zhao Huishan H Sun Fudong F Gong Zhaohua Z

Evidence-based complementary and alternative medicine : eCAM 20191129

Since the herb pair Huang Lian-Gan Jiang (HL-GJ) was put forward as conventional compatibility for cold-heat regulation in the middle energizer in the theory of Traditional Chinese Medicine (TCM), their therapeutic effects were observed on the prevention and treatment of intestinal inflammation and tumors including colorectal cancer (CRC). However, the active compounds, crucial targets, and related pathways of HL-GJ against CRC remained unclear. The purpose of this research was to establish a co ...[more]

PMID: 31871473

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Project description:BackgroundPharmacokinetic interaction is one of the most important indices for the evaluation of the compatibility of herbal medicines. Both Gancao (Glycyrrhizae Radix et Rhizoma) and Huanglian (Coptidis Rhizoma) are commonly used traditional Chinese medicines (TCMs). In this study, the influence of Gancao on the pharmacokinetics of Huanglian was systematically studied by using berberine as a pharmacokinetic marker.MethodsExtracts of the herbal pieces of Huanglian and the herb pair (Huanglian plus Gancao) were prepared with boiling water. The concentration of berberine in the samples was analyzed using liquid chromatography-mass spectrometry. The total amounts of berberine in all extract samples were compared. Comparative pharmacokinetic studies of Huanglian and the herb pair were conducted in ICR mice. In vitro berberine absorption and efflux were studied using mice gut sacs. The equilibrium solubility of berberine in the extracts was determined. The in vitro dissolution of berberine was comparatively studied using a rotating basket method.ResultsGancao significantly reduced berberine exposure in the portal circulation (425.8 ng·h/mL vs. 270.4 ng·h/mL) and the liver (29,500.8 ng·h/mL vs. 15,422.4 ng·h/mL) of the mice. In addition, Gancao decreased the peak concentration (Cmax) of berberine in the portal circulation (104.3 ng·h/mL vs. 76.5 ng·h/mL) and liver (4926.1 ng·h/mL vs. 2642.8 ng·h/mL) of mice. Significant influences of Gancao on the amount of berberine extracted (32% reduction), the solubility of berberine (34.7% compared with the control group), and dissolution (88.7% vs. 66.1% at 15 min in acid buffer and 68% vs. 51.8% at 15 min in phosphate buffer) were also revealed. Comparative pharmacokinetic studies in ICR mice indicated that the formation of sediment was unfavorable in terms of berberine absorption (345.3 ng·h/mL vs. 119.8 ng·h/mL).ConclusionsGancao was able to reduce intestinal absorption and in vivo exposure of berberine in Huanglian via the formation of sediment, which caused reductions in the extracted amount, solubility, and dissolution of berberine.

Project description:BackgroundCoronary heart disease (CHD) seriously affects human health, and its pathogenesis is closely related to atherosclerosis. The Huzhang (the root of Polygonum cuspidatum)-Shanzha (the fruit of Crataegus sp.), a classic herb pair, has been widely used for the treatment of CHD. In recent years, Huzhang-Shanzha herb pair (HSHP) was found to have a wide range of effects in CHD; however, its therapeutic specific mechanisms remain to be further explored. The aim of this study was to elucidate the molecular mechanism of HSHP in the treatment of CHD using a network pharmacology analysis approach.MethodsThe Batman-TCM database was used to explore bioactive compounds and corresponding targets of HSHP. CHD disease targets were extracted from Genecards, OMIM, PharmGkb, TTD, and DrugBank databases. Then, the protein-protein interaction (PPI) network was constructed using the STRING web platform and Cytoscape software. GO functional and KEGG pathway enrichment analyses were carried out on the Metascape web platform. Finally, molecular docking of the active components was assessed to verify the potential targets of HSHP to treat CHD by the AutoDock Vina and PyMOL software.ResultsTotally, 243 active components and 2459 corresponding targets of LDP were screened out. Eighty-five common targets of HSHP and CHD were identified. The results of the network analysis showed that resveratrol, anthranone, emodin, and ursolic acid could be defined as four therapeutic components. TNF, ESR1, NFКB1, PPARG, INS, TP53, NFКBIA, AR, PIK3R1, PIK3CA, PTGS2, and NR3C1 might be the 12 key targets. These targets were mainly involved in the regulation of biological processes, such as inflammatory responses and lipid metabolism. Enrichment analysis showed that the identified genes were mainly involved in fluid shear force, insulin resistance (IR), inflammation, and lipid metabolism pathways to contribute to CHD. This suggests that resveratrol, anthranone, emodin, and ursolic acid from HSHP can be the main therapeutic components of atherosclerosis.ConclusionUsing network pharmacology, we provide new clues on the potential mechanism of action of HSHP in the treatment of CHD, which may be closely related to the fluid shear force, lipid metabolism, and inflammatory response.

Project description:ObjectiveThe purpose of this work is to study the mechanism of action of Duhuo Jisheng Decoction (DHJSD) in the treatment of osteoporosis based on the methods of bioinformatics and network pharmacology.MethodsIn this study, the active compounds of each medicinal ingredient of DHJSD and their corresponding targets were obtained from TCMSP database. Osteoporosis was treated as search query in GeneCards, MalaCards, DisGeNET, Therapeutic Target Database (TTD), Comparative Toxicogenomics Database (CTD), and OMIM databases to obtain disease-related genes. The overlapping targets of DHJSD and osteoporosis were identified, and then GO and KEGG enrichment analysis were performed. Cytoscape was employed to construct DHJSD-compounds-target genes-osteoporosis network and protein-protein interaction (PPI) network. CytoHubba was utilized to select the hub genes. The activities of binding of hub genes and key components were confirmed by molecular docking.Results174 active compounds and their 205 related potential targets were identified in DHJSD for the treatment of osteoporosis, including 10 hub genes (AKT1, ALB, IL6, MAPK3, VEGFA, JUN, CASP3, EGFR, MYC, and EGF). Pathway enrichment analysis of target proteins indicated that osteoclast differentiation, AGE-RAGE signaling pathway in diabetic complications, Wnt signaling pathway, MAPK signaling pathway, PI3K-Akt signaling pathway, JAK-STAT signaling pathway, calcium signaling pathway, and TNF signaling pathway were the specifically major pathways regulated by DHJSD against osteoporosis. Further verification based on molecular docking results showed that the small molecule compounds (Quercetin, Kaempferol, Beta-sitosterol, Beta-carotene, and Formononetin) contained in DHJSD generally have excellent binding affinity to the macromolecular target proteins encoded by the top 10 genes.ConclusionThis study reveals the characteristics of multi-component, multi-target, and multi-pathway of DHJSD against osteoporosis and provides novel insights for verifying the mechanism of DHJSD in the treatment of osteoporosis.

Dataset Information

Exploring the Pharmacological Mechanism of the Herb Pair "HuangLian-GanJiang" against Colorectal Cancer Based on Network Pharmacology.

Publications

Exploring the Pharmacological Mechanism of the Herb Pair "HuangLian-GanJiang" against Colorectal Cancer Based on Network Pharmacology.

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