Crocin Ameliorates Diabetic Nephropathy through Regulating Metabolism, CYP4A11/PPARγ, and TGF-β/Smad Pathways in Mice.

IF 2.1 4区医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Current drug metabolism Pub Date : 2023-01-01 DOI:10.2174/0113892002257928231031113337

Wei Chen, Jinhao Su, Yubin Liu, Tianmei Gao, Xiaohui Ji, Hanzhou Li, Huajun Li, Yuansong Wang, Hui Zhang, Shuquan Lv

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Abstract

Introduction: Crocin is one of the main components of Crocus sativus L. and can alleviate oxidative stress and inflammation in diabetic nephropathy (DN). However, the specific mechanism by which crocin treats DN still needs to be further elucidated.

Method: In the present study, a mouse model of DN was first established to investigate the therapeutic effect of crocin on DN mice. Subsequently, non-targeted metabolomics techniques were used to analyze the mechanisms of action of crocin in the treatment of DN. The effects of crocin on CYP4A11/PPARγ and TGF-β/Smad pathway were also investigated.

Result: Results showed that crocin exhibited significant therapeutic and anti-inflammatory, and anti-oxidative effects on DN mice. In addition, the non-targeted metabolomics results indicated that crocin treatment affected several metabolites in kidney. These metabolites were mainly associated with biotin metabolism, riboflavin metabolism, and arachidonic acid metabolism. Furthermore, crocin treatment upregulated the decreased levels of CYP4A11 and phosphorylated PPARγ, and reduced the increased levels of TGF-β1 and phosphorylated Smad2/3 in the kidneys of DN mice.

Conclusion: In conclusion, our study validated the considerable therapeutic, anti-inflammatory, and antioxidative impacts of crocin on DN mice. The mechanism of crocin treatment may be related to the regulation of biotin riboflavin and arachidonic acid metabolism, the activation of CYP4A11/PPARγ pathway, and the inhibition of TGF-β/Smad pathway in the kidney.

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Crocin通过调节小鼠代谢、CYP4A11/PPARγ和TGF-β/Smad途径改善糖尿病肾病。

前言：番红花苷是番红花的主要成分之一，可减轻糖尿病肾病的氧化应激和炎症反应。然而，番红花苷治疗DN的具体机制仍有待进一步阐明。方法：建立DN小鼠模型，观察番红花苷对DN小鼠的治疗作用。随后，使用非靶向代谢组学技术分析番红花苷治疗DN的作用机制。番红花苷对CYP4A11/PPARγ和TGF-β/Smad通路的影响。结果：番红花苷对DN小鼠具有明显的治疗、抗炎、抗氧化作用。此外，非靶向代谢组学结果表明，番红花苷治疗影响了肾脏中的几种代谢产物。这些代谢产物主要与生物素代谢、核黄素代谢和花生四烯酸代谢有关。此外，番红花苷治疗上调了DN小鼠肾脏中CYP4A11和磷酸化PPARγ水平的降低，并降低了TGF-β1和磷酸化Smad2/3水平的升高。结论：总之，我们的研究验证了番红花苷对DN小鼠的显著治疗、抗炎和抗氧化作用。番红花苷治疗的机制可能与调节生物素核黄素和花生四烯酸代谢、激活CYP4A11/PPARγ通路以及抑制肾脏中TGF-β/Smad通路有关。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Current drug metabolism 医学-生化与分子生物学

CiteScore

4.30

自引率

4.30%

发文量

审稿时长

4-8 weeks

期刊介绍： Current Drug Metabolism aims to cover all the latest and outstanding developments in drug metabolism, pharmacokinetics, and drug disposition. The journal serves as an international forum for the publication of full-length/mini review, research articles and guest edited issues in drug metabolism. Current Drug Metabolism is an essential journal for academic, clinical, government and pharmaceutical scientists who wish to be kept informed and up-to-date with the most important developments. The journal covers the following general topic areas: pharmaceutics, pharmacokinetics, toxicology, and most importantly drug metabolism. More specifically, in vitro and in vivo drug metabolism of phase I and phase II enzymes or metabolic pathways; drug-drug interactions and enzyme kinetics; pharmacokinetics, pharmacokinetic-pharmacodynamic modeling, and toxicokinetics; interspecies differences in metabolism or pharmacokinetics, species scaling and extrapolations; drug transporters; target organ toxicity and interindividual variability in drug exposure-response; extrahepatic metabolism; bioactivation, reactive metabolites, and developments for the identification of drug metabolites. Preclinical and clinical reviews describing the drug metabolism and pharmacokinetics of marketed drugs or drug classes.