Study on the Potential Mechanism of Tonifying Kidney and Removing Dampness Formula in the Treatment of Postmenopausal Dyslipidemia Based on Network Pharmacology, Molecular Docking and Experimental Evidence
BackgroundManagement of menopausal dyslipidemia is the main measure to reduce the incidence of cardiovascular disease in postmenopausal women. Tonifying Kidney and Removing Dampness Formula (TKRDF) is a traditional Chinese medicine (TCM) formula that ameliorates dyslipidemia in postmenopausal women....
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Frontiers Media S.A.
2022-07-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2022.918469/full |
| _version_ | 1811325808681156608 |
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| author | Xuewen Li Xuewen Li Hongyan Chen Hongyan Yang Jian Liu Yang Li Yue Dang Jiajing Wang Lei Wang Lei Wang Jun Li Guangning Nie Guangning Nie |
| author_facet | Xuewen Li Xuewen Li Hongyan Chen Hongyan Yang Jian Liu Yang Li Yue Dang Jiajing Wang Lei Wang Lei Wang Jun Li Guangning Nie Guangning Nie |
| author_sort | Xuewen Li |
| collection | DOAJ |
| description | BackgroundManagement of menopausal dyslipidemia is the main measure to reduce the incidence of cardiovascular disease in postmenopausal women. Tonifying Kidney and Removing Dampness Formula (TKRDF) is a traditional Chinese medicine (TCM) formula that ameliorates dyslipidemia in postmenopausal women. This study applied network pharmacology, molecular docking, and in vitro and in vitro experiments to investigate the underlying mechanism of TKRDF against postmenopausal dyslipidemia.MethodsNetwork pharmacology research was first conducted, and the active compounds and targets of TKRDF, as well as the targets of postmenopausal dyslipidemia, were extracted from public databases. Protein–protein interaction (PPI), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were used to identify the potential targets and signaling pathways of TKRDF in postmenopausal dyslipidemia. Molecular docking was then performed to evaluate the combination of active compounds with principal targets. Finally, an ovariectomized rat model was used for the in vivo experiment and alpha mouse liver 12 (AML12) cells treated with palmitic acid were used for the in vitro experiments to provide further evidence for the research.ResultsBased on network pharmacology analysis, we obtained 78 active compounds from TKRDF that acted on 222 targets of postmenopausal dyslipidemia. The analysis results indicated that IL6, TNF, VEGFA, AKT1, MAPK3, MAPK1, PPARG and PIK3CA, etc., were the potentially key targets, and the PI3K/AKT signaling pathway was the possibly crucial pathway for TKRDF to treat postmenopausal dyslipidemia. Molecular docking suggested that the active compounds have good binding activity with the core targets. The in vivo and in vitro experiments demonstrated that TKRDF ameliorates postmenopausal dyslipidemia by regulating hormone levels, inhibiting inflammation, promoting angiogenesis and inhibiting lipid synthesis, which appear to be related to TKRDF’s regulation of the ERK1/2 and PI3K/AKT signaling pathways.ConclusionThis study clarified the active ingredients, potential targets, and molecular mechanisms of TKRDF for treating postmenopausal dyslipidemia. It also provided a feasible method to uncover the scientific basis and therapeutic mechanism for prescribing TCM in the treatment of diseases. |
| first_indexed | 2024-04-13T14:39:16Z |
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| id | doaj.art-e624546c9b104524ab5d6da5b5a7096d |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-04-13T14:39:16Z |
| publishDate | 2022-07-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Endocrinology |
| spelling | doaj.art-e624546c9b104524ab5d6da5b5a7096d2022-12-22T02:42:57ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922022-07-011310.3389/fendo.2022.918469918469Study on the Potential Mechanism of Tonifying Kidney and Removing Dampness Formula in the Treatment of Postmenopausal Dyslipidemia Based on Network Pharmacology, Molecular Docking and Experimental EvidenceXuewen Li0Xuewen Li1Hongyan Chen2Hongyan Yang3Jian Liu4Yang Li5Yue Dang6Jiajing Wang7Lei Wang8Lei Wang9Jun Li10Guangning Nie11Guangning Nie12State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, ChinaDepartment of Cardiovascular Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, ChinaThe Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, ChinaDepartment of Gynecology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, ChinaDepartment of Gynecology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, ChinaDepartment of Gynecology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, ChinaCollege of Traditional Chinese Medicine, Shenyang Pharmaceutical University, Shenyang, ChinaThe Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, ChinaState Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, ChinaDepartment of Cardiovascular Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, ChinaState Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, ChinaState Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, ChinaDepartment of Gynecology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, ChinaBackgroundManagement of menopausal dyslipidemia is the main measure to reduce the incidence of cardiovascular disease in postmenopausal women. Tonifying Kidney and Removing Dampness Formula (TKRDF) is a traditional Chinese medicine (TCM) formula that ameliorates dyslipidemia in postmenopausal women. This study applied network pharmacology, molecular docking, and in vitro and in vitro experiments to investigate the underlying mechanism of TKRDF against postmenopausal dyslipidemia.MethodsNetwork pharmacology research was first conducted, and the active compounds and targets of TKRDF, as well as the targets of postmenopausal dyslipidemia, were extracted from public databases. Protein–protein interaction (PPI), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were used to identify the potential targets and signaling pathways of TKRDF in postmenopausal dyslipidemia. Molecular docking was then performed to evaluate the combination of active compounds with principal targets. Finally, an ovariectomized rat model was used for the in vivo experiment and alpha mouse liver 12 (AML12) cells treated with palmitic acid were used for the in vitro experiments to provide further evidence for the research.ResultsBased on network pharmacology analysis, we obtained 78 active compounds from TKRDF that acted on 222 targets of postmenopausal dyslipidemia. The analysis results indicated that IL6, TNF, VEGFA, AKT1, MAPK3, MAPK1, PPARG and PIK3CA, etc., were the potentially key targets, and the PI3K/AKT signaling pathway was the possibly crucial pathway for TKRDF to treat postmenopausal dyslipidemia. Molecular docking suggested that the active compounds have good binding activity with the core targets. The in vivo and in vitro experiments demonstrated that TKRDF ameliorates postmenopausal dyslipidemia by regulating hormone levels, inhibiting inflammation, promoting angiogenesis and inhibiting lipid synthesis, which appear to be related to TKRDF’s regulation of the ERK1/2 and PI3K/AKT signaling pathways.ConclusionThis study clarified the active ingredients, potential targets, and molecular mechanisms of TKRDF for treating postmenopausal dyslipidemia. It also provided a feasible method to uncover the scientific basis and therapeutic mechanism for prescribing TCM in the treatment of diseases.https://www.frontiersin.org/articles/10.3389/fendo.2022.918469/fullTCMpostmenopausal dyslipidemiatonifying kidney and removing dampness formulanetwork pharmacologymolecular dockingpharmacological mechanisms |
| spellingShingle | Xuewen Li Xuewen Li Hongyan Chen Hongyan Yang Jian Liu Yang Li Yue Dang Jiajing Wang Lei Wang Lei Wang Jun Li Guangning Nie Guangning Nie Study on the Potential Mechanism of Tonifying Kidney and Removing Dampness Formula in the Treatment of Postmenopausal Dyslipidemia Based on Network Pharmacology, Molecular Docking and Experimental Evidence Frontiers in Endocrinology TCM postmenopausal dyslipidemia tonifying kidney and removing dampness formula network pharmacology molecular docking pharmacological mechanisms |
| title | Study on the Potential Mechanism of Tonifying Kidney and Removing Dampness Formula in the Treatment of Postmenopausal Dyslipidemia Based on Network Pharmacology, Molecular Docking and Experimental Evidence |
| title_full | Study on the Potential Mechanism of Tonifying Kidney and Removing Dampness Formula in the Treatment of Postmenopausal Dyslipidemia Based on Network Pharmacology, Molecular Docking and Experimental Evidence |
| title_fullStr | Study on the Potential Mechanism of Tonifying Kidney and Removing Dampness Formula in the Treatment of Postmenopausal Dyslipidemia Based on Network Pharmacology, Molecular Docking and Experimental Evidence |
| title_full_unstemmed | Study on the Potential Mechanism of Tonifying Kidney and Removing Dampness Formula in the Treatment of Postmenopausal Dyslipidemia Based on Network Pharmacology, Molecular Docking and Experimental Evidence |
| title_short | Study on the Potential Mechanism of Tonifying Kidney and Removing Dampness Formula in the Treatment of Postmenopausal Dyslipidemia Based on Network Pharmacology, Molecular Docking and Experimental Evidence |
| title_sort | study on the potential mechanism of tonifying kidney and removing dampness formula in the treatment of postmenopausal dyslipidemia based on network pharmacology molecular docking and experimental evidence |
| topic | TCM postmenopausal dyslipidemia tonifying kidney and removing dampness formula network pharmacology molecular docking pharmacological mechanisms |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2022.918469/full |
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