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桑白皮总黄酮对乳清酸诱导的非酒精性脂肪性肝病大鼠肝胆固醇代谢紊乱的调节作用。

Regulation effects of total flavonoids in Morus alba L. on hepatic cholesterol disorders in orotic acid induced NAFLD rats.

机构信息

Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China.

Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China.

出版信息

BMC Complement Med Ther. 2020 Aug 17;20(1):257. doi: 10.1186/s12906-020-03052-w.

Abstract

BACKGROUND

Mulberry leaves are the dried leaves of Morus alba L., flavonoids from mulberry leaves (MLF) has showed regulatory effect on abnormal lipid metabolism, but the regulatory mechanism of MLF on cholesterol metabolism is still missing. This study was designed to investigate the effect of MLF and its active metabolite quercetin on regulating cholesterol disorders.

METHODS

The mechanism of MLF on alleviating liver injury and regulating cholesterol was examined in dyslipidemic SD rats. The regulatory mechanism of quercetin for cholesterol disorders have also been detected through lipid laden HepG2 cell model.

RESULTS

Our results showed that MLF significantly inhibited lipid accumulation and alleviate hepatic injury in NAFLD rat model. The hepatic expression level of SREBP2, HMGCR and miR-33a were significantly down-regulated, while CYP7A1 was induced by MLF treatment. In vitro, Quercetin significantly decreased lipid accumulation in HepG2 cells. Mechanistically, quercetin could inhibit the mRNA and protein expression level of SREBP2 and HMGCR with or without LDL treatment. In addition, quercetin could also reduce the LXRβ while induced SR-BI mRNA expression.

CONCLUSION

Our findings indicate that MLF and quercetin could reduce the excessive cholesterol accumulation in vivo and in vitro. These cholesterol-regulating phenomenon might attribute to its effect on down-regulating the expression of lipid-related markers such as SREBP2 and HMGCR, which may exert a protective role in the NAFLD treatment.

摘要

背景

桑叶是桑科植物桑的干燥叶,桑叶中的黄酮类化合物对异常脂质代谢具有调节作用,但桑叶黄酮类化合物(MLF)调节胆固醇代谢的机制尚不清楚。本研究旨在探讨 MLF 及其活性代谢物槲皮素调节胆固醇代谢紊乱的作用。

方法

采用高脂血症 SD 大鼠模型,考察 MLF 缓解肝损伤和调节胆固醇的作用机制。通过载脂 HepG2 细胞模型检测槲皮素调节胆固醇紊乱的作用机制。

结果

结果表明,MLF 能显著抑制 NAFLD 大鼠模型的脂质蓄积,减轻肝损伤。MLF 处理后 SREBP2、HMGCR 和 miR-33a 的肝表达水平显著下调,而 CYP7A1 则被诱导。体外,槲皮素可显著减少 HepG2 细胞的脂质蓄积。在机制上,槲皮素可抑制 SREBP2 和 HMGCR 的 mRNA 和蛋白表达水平,无论是否有 LDL 处理。此外,槲皮素还可以降低 LXRβ,同时诱导 SR-BI mRNA 表达。

结论

本研究结果表明,MLF 和槲皮素可减少体内和体外过量的胆固醇蓄积。这些调节胆固醇的现象可能归因于其下调脂质相关标志物如 SREBP2 和 HMGCR 的表达,这可能在 NAFLD 的治疗中发挥保护作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa51/7433163/a92d0625c438/12906_2020_3052_Fig1_HTML.jpg

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