Network Pharmacology Based Research on the Combination Mechanism Between Escin and Low Dose Glucocorticoids in Anti-rheumatoid Arthritis
Rheumatoid arthritis (RA) is characterized by chronic progressive symmetrical synovitis and destruction of multiple joints. Glucocorticoids (GCs) are widely used in the treatment of RA. However, their adverse effects can be serious. Escin, which is isolated from Aesculus hippocastanum L., has been r...
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| Format: | Article |
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Frontiers Media S.A.
2019-03-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fphar.2019.00280/full |
| _version_ | 1818671334777946112 |
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| author | Leiming Zhang Yanan Huang Chuanhong Wu Yuan Du Peng Li Meiling Wang Xinlin Wang Yanfang Wang Yanfei Hao Tian Wang Baofeng Fan Zhuye Gao Fenghua Fu |
| author_facet | Leiming Zhang Yanan Huang Chuanhong Wu Yuan Du Peng Li Meiling Wang Xinlin Wang Yanfang Wang Yanfei Hao Tian Wang Baofeng Fan Zhuye Gao Fenghua Fu |
| author_sort | Leiming Zhang |
| collection | DOAJ |
| description | Rheumatoid arthritis (RA) is characterized by chronic progressive symmetrical synovitis and destruction of multiple joints. Glucocorticoids (GCs) are widely used in the treatment of RA. However, their adverse effects can be serious. Escin, which is isolated from Aesculus hippocastanum L., has been reported to have anti-inflammatory effects. We investigated the anti-RA effect of Escin combined with low dose GCs (dexamethasone, Dex) and the underlying mechanism. Adjuvant-induced RA rats and lipopolysaccharides (LPS)-injured RAW264.7 cells were used to investigate the anti-RA effects of Escin combined with low dose Dex in vivo and in vitro. The results showed that Escin combined with low-dose Dex significantly decreased arthritic index, serum IL-6 and TNF-α levels, reduced paw swelling, and ameliorated the joint pathology and immune organ pathology. Gene chip results revealed that Nr3c1 (GR) expression was significantly altered, and that GR was activated by Escin and low dose Dex in vivo and in vitro. Additionally, Escin combined with low dose Dex also significantly increased GR mRNA expression. However, when GR expression was suppressed by its specific inhibitor, the anti-RA effect of Escin combined with low-dose Dex was abolished. The data in this study demonstrated that Escin combined with Dex reduced the dose of Dex, and exerted significant anti-RA effects, which could also reduce the adverse effects of Dex. This combination might result from GR activation. This study might provide a new combination of drugs for the treatment of RA. |
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| id | doaj.art-51fe0f1dfa704fd3bcbbb5a6ddf9d10b |
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| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-17T07:22:21Z |
| publishDate | 2019-03-01 |
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| series | Frontiers in Pharmacology |
| spelling | doaj.art-51fe0f1dfa704fd3bcbbb5a6ddf9d10b2022-12-21T21:58:43ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122019-03-011010.3389/fphar.2019.00280441895Network Pharmacology Based Research on the Combination Mechanism Between Escin and Low Dose Glucocorticoids in Anti-rheumatoid ArthritisLeiming Zhang0Yanan Huang1Chuanhong Wu2Yuan Du3Peng Li4Meiling Wang5Xinlin Wang6Yanfang Wang7Yanfei Hao8Tian Wang9Baofeng Fan10Zhuye Gao11Fenghua Fu12Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, School of Pharmacy, Yantai University, Yantai, ChinaKey Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, School of Pharmacy, Yantai University, Yantai, ChinaThe Biomedical Sciences Institute of Qingdao University (Qingdao Branch of SJTU Bio-X Institutes), Qingdao University, Qingdao, ChinaKey Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, School of Pharmacy, Yantai University, Yantai, ChinaCollege of Arts and Sciences, Shanxi Agricultural University, Taigu, ChinaKey Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, School of Pharmacy, Yantai University, Yantai, ChinaKey Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, School of Pharmacy, Yantai University, Yantai, ChinaKey Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, School of Pharmacy, Yantai University, Yantai, ChinaKey Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, School of Pharmacy, Yantai University, Yantai, ChinaKey Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, School of Pharmacy, Yantai University, Yantai, ChinaAir Force General Hospital, PLA, Beijing, ChinaXiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, ChinaKey Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, School of Pharmacy, Yantai University, Yantai, ChinaRheumatoid arthritis (RA) is characterized by chronic progressive symmetrical synovitis and destruction of multiple joints. Glucocorticoids (GCs) are widely used in the treatment of RA. However, their adverse effects can be serious. Escin, which is isolated from Aesculus hippocastanum L., has been reported to have anti-inflammatory effects. We investigated the anti-RA effect of Escin combined with low dose GCs (dexamethasone, Dex) and the underlying mechanism. Adjuvant-induced RA rats and lipopolysaccharides (LPS)-injured RAW264.7 cells were used to investigate the anti-RA effects of Escin combined with low dose Dex in vivo and in vitro. The results showed that Escin combined with low-dose Dex significantly decreased arthritic index, serum IL-6 and TNF-α levels, reduced paw swelling, and ameliorated the joint pathology and immune organ pathology. Gene chip results revealed that Nr3c1 (GR) expression was significantly altered, and that GR was activated by Escin and low dose Dex in vivo and in vitro. Additionally, Escin combined with low dose Dex also significantly increased GR mRNA expression. However, when GR expression was suppressed by its specific inhibitor, the anti-RA effect of Escin combined with low-dose Dex was abolished. The data in this study demonstrated that Escin combined with Dex reduced the dose of Dex, and exerted significant anti-RA effects, which could also reduce the adverse effects of Dex. This combination might result from GR activation. This study might provide a new combination of drugs for the treatment of RA.https://www.frontiersin.org/article/10.3389/fphar.2019.00280/fullrheumatoid arthritisglucocorticoidsglucocorticoid receptorEscindexamethasone |
| spellingShingle | Leiming Zhang Yanan Huang Chuanhong Wu Yuan Du Peng Li Meiling Wang Xinlin Wang Yanfang Wang Yanfei Hao Tian Wang Baofeng Fan Zhuye Gao Fenghua Fu Network Pharmacology Based Research on the Combination Mechanism Between Escin and Low Dose Glucocorticoids in Anti-rheumatoid Arthritis Frontiers in Pharmacology rheumatoid arthritis glucocorticoids glucocorticoid receptor Escin dexamethasone |
| title | Network Pharmacology Based Research on the Combination Mechanism Between Escin and Low Dose Glucocorticoids in Anti-rheumatoid Arthritis |
| title_full | Network Pharmacology Based Research on the Combination Mechanism Between Escin and Low Dose Glucocorticoids in Anti-rheumatoid Arthritis |
| title_fullStr | Network Pharmacology Based Research on the Combination Mechanism Between Escin and Low Dose Glucocorticoids in Anti-rheumatoid Arthritis |
| title_full_unstemmed | Network Pharmacology Based Research on the Combination Mechanism Between Escin and Low Dose Glucocorticoids in Anti-rheumatoid Arthritis |
| title_short | Network Pharmacology Based Research on the Combination Mechanism Between Escin and Low Dose Glucocorticoids in Anti-rheumatoid Arthritis |
| title_sort | network pharmacology based research on the combination mechanism between escin and low dose glucocorticoids in anti rheumatoid arthritis |
| topic | rheumatoid arthritis glucocorticoids glucocorticoid receptor Escin dexamethasone |
| url | https://www.frontiersin.org/article/10.3389/fphar.2019.00280/full |
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