Dioscin Ameliorates Hyperuricemia-Induced Atherosclerosis by Modulating of Cholesterol Metabolism through FXR-Signaling Pathway
Hyperuricemia is one of the independent risk factors for atherosclerotic cardiovascular disease. Herein, we investigate the association between uric acid and cholesterol metabolism and the effect of dioscin on the prevention of hyperuricemia-induced atherosclerosis. In the potassium oxonate-treated...
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MDPI AG
2022-05-01
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| Online Access: | https://www.mdpi.com/2072-6643/14/9/1983 |
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| author | Ruixia Bao Wei Wang Beibei Chen Jujie Pan Qian Chen Mengyang Liu Dan Wang Yuzheng Wu Haiyang Yu Lifeng Han Yi Zhang Tao Wang |
| author_facet | Ruixia Bao Wei Wang Beibei Chen Jujie Pan Qian Chen Mengyang Liu Dan Wang Yuzheng Wu Haiyang Yu Lifeng Han Yi Zhang Tao Wang |
| author_sort | Ruixia Bao |
| collection | DOAJ |
| description | Hyperuricemia is one of the independent risk factors for atherosclerotic cardiovascular disease. Herein, we investigate the association between uric acid and cholesterol metabolism and the effect of dioscin on the prevention of hyperuricemia-induced atherosclerosis. In the potassium oxonate-treated ApoE<sup>−/−−/−</sup> mice, atherosclerosis was accelerated along with elevated serum cholesterol levels in the hyperuricemic state, which can be ameliorated by dioscin. Together with the in vitro assays, we found that the effect of dioscin was at least partially through the regulation of the farnesoid X receptor (FXR) -small heterodimer partner (SHP) -7α-hydroxylase (CYP7A1) signaling pathway in the liver. Tigogenin (a metabolite of dioscin) suppressed FXR activation and increased CYP7A1, resulting in an increased conversion rate of cholesterols into bile acids. Further clinical study revealed that treatment with a dioscin-enriched preparation decreased serum cholesterol levels in individuals with hyperuricemia. In summary, this study demonstrated a slowdown effect of dioscin on the progression of hyperuricemia-induced atherosclerosis. |
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| institution | Directory Open Access Journal |
| issn | 2072-6643 |
| language | English |
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| spelling | doaj.art-2629cfc62913443f8e489981ccb8f07f2023-11-23T09:01:23ZengMDPI AGNutrients2072-66432022-05-01149198310.3390/nu14091983Dioscin Ameliorates Hyperuricemia-Induced Atherosclerosis by Modulating of Cholesterol Metabolism through FXR-Signaling PathwayRuixia Bao0Wei Wang1Beibei Chen2Jujie Pan3Qian Chen4Mengyang Liu5Dan Wang6Yuzheng Wu7Haiyang Yu8Lifeng Han9Yi Zhang10Tao Wang11State Key Laboratory of Component-Based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 10 Poyanghu Road, Jinghai District, Tianjin 301617, ChinaInternal Medicine, University of Texas Medical Branch, 301 University Blvd, Galveston, TX 77555, USAState Key Laboratory of Component-Based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 10 Poyanghu Road, Jinghai District, Tianjin 301617, ChinaInstitute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 10 Poyanghu Road, Jinghai District, Tianjin 301617, ChinaInstitute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 10 Poyanghu Road, Jinghai District, Tianjin 301617, ChinaState Key Laboratory of Component-Based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 10 Poyanghu Road, Jinghai District, Tianjin 301617, ChinaKey Laboratory of Pharmacology of Traditional Chinese Medical Formulae (Tianjin University of Traditional Chinese Medicine), Ministry of Education, 312 Anshanxi Road, Nankai District, Tianjin 300193, ChinaInstitute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 10 Poyanghu Road, Jinghai District, Tianjin 301617, ChinaState Key Laboratory of Component-Based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 10 Poyanghu Road, Jinghai District, Tianjin 301617, ChinaState Key Laboratory of Component-Based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 10 Poyanghu Road, Jinghai District, Tianjin 301617, ChinaState Key Laboratory of Component-Based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 10 Poyanghu Road, Jinghai District, Tianjin 301617, ChinaState Key Laboratory of Component-Based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 10 Poyanghu Road, Jinghai District, Tianjin 301617, ChinaHyperuricemia is one of the independent risk factors for atherosclerotic cardiovascular disease. Herein, we investigate the association between uric acid and cholesterol metabolism and the effect of dioscin on the prevention of hyperuricemia-induced atherosclerosis. In the potassium oxonate-treated ApoE<sup>−/−−/−</sup> mice, atherosclerosis was accelerated along with elevated serum cholesterol levels in the hyperuricemic state, which can be ameliorated by dioscin. Together with the in vitro assays, we found that the effect of dioscin was at least partially through the regulation of the farnesoid X receptor (FXR) -small heterodimer partner (SHP) -7α-hydroxylase (CYP7A1) signaling pathway in the liver. Tigogenin (a metabolite of dioscin) suppressed FXR activation and increased CYP7A1, resulting in an increased conversion rate of cholesterols into bile acids. Further clinical study revealed that treatment with a dioscin-enriched preparation decreased serum cholesterol levels in individuals with hyperuricemia. In summary, this study demonstrated a slowdown effect of dioscin on the progression of hyperuricemia-induced atherosclerosis.https://www.mdpi.com/2072-6643/14/9/1983dioscintigogeninhyperuricemiaatherosclerosischolesterolbile acid |
| spellingShingle | Ruixia Bao Wei Wang Beibei Chen Jujie Pan Qian Chen Mengyang Liu Dan Wang Yuzheng Wu Haiyang Yu Lifeng Han Yi Zhang Tao Wang Dioscin Ameliorates Hyperuricemia-Induced Atherosclerosis by Modulating of Cholesterol Metabolism through FXR-Signaling Pathway Nutrients dioscin tigogenin hyperuricemia atherosclerosis cholesterol bile acid |
| title | Dioscin Ameliorates Hyperuricemia-Induced Atherosclerosis by Modulating of Cholesterol Metabolism through FXR-Signaling Pathway |
| title_full | Dioscin Ameliorates Hyperuricemia-Induced Atherosclerosis by Modulating of Cholesterol Metabolism through FXR-Signaling Pathway |
| title_fullStr | Dioscin Ameliorates Hyperuricemia-Induced Atherosclerosis by Modulating of Cholesterol Metabolism through FXR-Signaling Pathway |
| title_full_unstemmed | Dioscin Ameliorates Hyperuricemia-Induced Atherosclerosis by Modulating of Cholesterol Metabolism through FXR-Signaling Pathway |
| title_short | Dioscin Ameliorates Hyperuricemia-Induced Atherosclerosis by Modulating of Cholesterol Metabolism through FXR-Signaling Pathway |
| title_sort | dioscin ameliorates hyperuricemia induced atherosclerosis by modulating of cholesterol metabolism through fxr signaling pathway |
| topic | dioscin tigogenin hyperuricemia atherosclerosis cholesterol bile acid |
| url | https://www.mdpi.com/2072-6643/14/9/1983 |
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