Dioscin Ameliorates Hyperuricemia-Induced Atherosclerosis by Modulating of Cholesterol Metabolism through FXR-Signaling Pathway.

Abstract

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-/--/- 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.

• Authors: Ruixia Bao, Wei Wang, Beibei Chen, Jujie Pan, Qian Chen, Mengyang Liu, Dan Wang, Yuzheng Wu, Haiyang Yu, Lifeng Han, Yi Zhang, Tao Wang
• Journal: Nutrients (Nutrients) Vol. 14 Issue 9 (May 09 2022) ISSN: 2072-6643 [Electronic] Switzerland
• PMID: 35565954 (Publication Type: Journal Article)

Chemical References

• Bile Acids and Salts
• dioscin
• Cholesterol
• Cholesterol 7-alpha-Hydroxylase
• Diosgenin

Topics

• Animals
• Atherosclerosis (drug therapy, etiology, prevention & control)
• Bile Acids and Salts (metabolism)
• Cholesterol
• Cholesterol 7-alpha-Hydroxylase (metabolism)
• Diosgenin (analogs & derivatives)
• Hyperuricemia (complications, drug therapy)
• Liver (metabolism)
• Mice
• Signal Transduction