WTD Attenuating Rheumatoid Arthritis via Suppressing Angiogenesis and Modulating the PI3K/AKT/mTOR/HIF-1α Pathway
Background: Wutou Decoction (WTD), as a classic prescription, has been generally used to treat rheumatoid arthritis (RA) for two thousand years in China. However, the potential protective effects of WTD on rheumatoid arthritis and its possible mechanism have rarely been reported.Purpose: The aim of...
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Frontiers Media S.A.
2021-09-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2021.696802/full |
| _version_ | 1818361816118460416 |
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| author | Xin Ba Ying Huang Ying Huang Pan Shen Yao Huang Hui Wang Liang Han Wei Ji Lin Hui Jia Yan Li Jun Xu Kai Qin Zhe Chen Zhe Chen Sheng Hao Tu Sheng Hao Tu |
| author_facet | Xin Ba Ying Huang Ying Huang Pan Shen Yao Huang Hui Wang Liang Han Wei Ji Lin Hui Jia Yan Li Jun Xu Kai Qin Zhe Chen Zhe Chen Sheng Hao Tu Sheng Hao Tu |
| author_sort | Xin Ba |
| collection | DOAJ |
| description | Background: Wutou Decoction (WTD), as a classic prescription, has been generally used to treat rheumatoid arthritis (RA) for two thousand years in China. However, the potential protective effects of WTD on rheumatoid arthritis and its possible mechanism have rarely been reported.Purpose: The aim of this study was to explore the possible mechanism of WTD against RA and a promising alternative candidate for RA therapy.Methods: A model of collagen-induced arthritis (CIA) was constructed in rats to assess the therapeutic effects of WTD. Histopathological staining, immunofluorescence, and western blotting of synovial sections were conducted to detect the antiangiogenic effects of WTD. Then, cell viability assays, flow cytometry, scratch healing assays, and invasion assays were conducted to explore the effects of WTD on MH7A human fibroblast-like synoviocyte (FLS) cell proliferation, apoptosis, migration, and invasion in vitro. The ability of WTD to induce blood vessel formation after MH7A cell and human umbilical vein endothelial cell line (HUVEC) coculture with WTD intervention was detected by a tube formation assay. The mechanisms of WTD were screened by network pharmacology and confirmed by in vivo and in vitro experiments.Results: WTD ameliorated the symptoms and synovial pannus hyperplasia of CIA rats. Treatment with WTD inhibited MH7A cell proliferation, migration, and invasion and promoted MH7A apoptosis. WTD could inhibit MH7A cell expression of proangiogenic factors, including VEGF and ANGI, to induce HUVEC tube formation. Furthermore, the PI3K-AKT-mTOR-HIF-1α pathway was enriched as a potential target of WTD for the treatment of RA through network pharmacology enrichment analysis. Finally, it was confirmed in vitro and in vivo that WTD inhibits angiogenesis in RA by interrupting the PI3K-AKT-mTOR-HIF-1α pathway.Conclusion: WTD can inhibit synovial hyperplasia and angiogenesis, presumably by inhibiting the migration and invasion of MH7A cells and blocking the production of proangiogenic effectors in MH7A cells. The possible underlying mechanism by which WTD ameliorates angiogenesis in RA is the PI3K-AKT-mTOR-HIF-1α pathway. |
| first_indexed | 2024-12-13T21:22:41Z |
| format | Article |
| id | doaj.art-51c130daf33d467ab725e43d5395ad27 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-13T21:22:41Z |
| publishDate | 2021-09-01 |
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| series | Frontiers in Pharmacology |
| spelling | doaj.art-51c130daf33d467ab725e43d5395ad272022-12-21T23:31:02ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122021-09-011210.3389/fphar.2021.696802696802WTD Attenuating Rheumatoid Arthritis via Suppressing Angiogenesis and Modulating the PI3K/AKT/mTOR/HIF-1α PathwayXin Ba0Ying Huang1Ying Huang2Pan Shen3Yao Huang4Hui Wang5Liang Han6Wei Ji Lin7Hui Jia Yan8Li Jun Xu9Kai Qin10Zhe Chen11Zhe Chen12Sheng Hao Tu13Sheng Hao Tu14Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaInstitute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaInstitute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaInstitute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaRehabilitation and Sports Medicine Research Institute of Zhejiang Province, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, ChinaInstitute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaInstitute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaInstitute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaInstitute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaInstitute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaInstitute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaBackground: Wutou Decoction (WTD), as a classic prescription, has been generally used to treat rheumatoid arthritis (RA) for two thousand years in China. However, the potential protective effects of WTD on rheumatoid arthritis and its possible mechanism have rarely been reported.Purpose: The aim of this study was to explore the possible mechanism of WTD against RA and a promising alternative candidate for RA therapy.Methods: A model of collagen-induced arthritis (CIA) was constructed in rats to assess the therapeutic effects of WTD. Histopathological staining, immunofluorescence, and western blotting of synovial sections were conducted to detect the antiangiogenic effects of WTD. Then, cell viability assays, flow cytometry, scratch healing assays, and invasion assays were conducted to explore the effects of WTD on MH7A human fibroblast-like synoviocyte (FLS) cell proliferation, apoptosis, migration, and invasion in vitro. The ability of WTD to induce blood vessel formation after MH7A cell and human umbilical vein endothelial cell line (HUVEC) coculture with WTD intervention was detected by a tube formation assay. The mechanisms of WTD were screened by network pharmacology and confirmed by in vivo and in vitro experiments.Results: WTD ameliorated the symptoms and synovial pannus hyperplasia of CIA rats. Treatment with WTD inhibited MH7A cell proliferation, migration, and invasion and promoted MH7A apoptosis. WTD could inhibit MH7A cell expression of proangiogenic factors, including VEGF and ANGI, to induce HUVEC tube formation. Furthermore, the PI3K-AKT-mTOR-HIF-1α pathway was enriched as a potential target of WTD for the treatment of RA through network pharmacology enrichment analysis. Finally, it was confirmed in vitro and in vivo that WTD inhibits angiogenesis in RA by interrupting the PI3K-AKT-mTOR-HIF-1α pathway.Conclusion: WTD can inhibit synovial hyperplasia and angiogenesis, presumably by inhibiting the migration and invasion of MH7A cells and blocking the production of proangiogenic effectors in MH7A cells. The possible underlying mechanism by which WTD ameliorates angiogenesis in RA is the PI3K-AKT-mTOR-HIF-1α pathway.https://www.frontiersin.org/articles/10.3389/fphar.2021.696802/fullrheumatoid arthritisfibroblast-like synoviocyteswutou decoctionangiogenesiscollagen-induced arthritisnetwork pharmacology |
| spellingShingle | Xin Ba Ying Huang Ying Huang Pan Shen Yao Huang Hui Wang Liang Han Wei Ji Lin Hui Jia Yan Li Jun Xu Kai Qin Zhe Chen Zhe Chen Sheng Hao Tu Sheng Hao Tu WTD Attenuating Rheumatoid Arthritis via Suppressing Angiogenesis and Modulating the PI3K/AKT/mTOR/HIF-1α Pathway Frontiers in Pharmacology rheumatoid arthritis fibroblast-like synoviocytes wutou decoction angiogenesis collagen-induced arthritis network pharmacology |
| title | WTD Attenuating Rheumatoid Arthritis via Suppressing Angiogenesis and Modulating the PI3K/AKT/mTOR/HIF-1α Pathway |
| title_full | WTD Attenuating Rheumatoid Arthritis via Suppressing Angiogenesis and Modulating the PI3K/AKT/mTOR/HIF-1α Pathway |
| title_fullStr | WTD Attenuating Rheumatoid Arthritis via Suppressing Angiogenesis and Modulating the PI3K/AKT/mTOR/HIF-1α Pathway |
| title_full_unstemmed | WTD Attenuating Rheumatoid Arthritis via Suppressing Angiogenesis and Modulating the PI3K/AKT/mTOR/HIF-1α Pathway |
| title_short | WTD Attenuating Rheumatoid Arthritis via Suppressing Angiogenesis and Modulating the PI3K/AKT/mTOR/HIF-1α Pathway |
| title_sort | wtd attenuating rheumatoid arthritis via suppressing angiogenesis and modulating the pi3k akt mtor hif 1α pathway |
| topic | rheumatoid arthritis fibroblast-like synoviocytes wutou decoction angiogenesis collagen-induced arthritis network pharmacology |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2021.696802/full |
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