Format

Send to

Choose Destination
Chem Biol Interact. 2019 Jul 1;307:116-124. doi: 10.1016/j.cbi.2019.05.004. Epub 2019 May 4.

Activation of 20-HETE/PPARs involved in reno-therapeutic effect of naringenin on diabetic nephropathy.

Author information

1
Department of Pharmacology, Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing Medical University, Chongqing, 400016, PR China.
2
Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, Guizhou, 563003, PR China.
3
Department of Nephrology, The Fifth Affiliated Hospital, Zunyi Medical University, Zhuhai, Guangdong, 519100, PR China.
4
Department of Neurology, First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, PR China.
5
Department of Pharmacology, Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing Medical University, Chongqing, 400016, PR China. Electronic address: cqjiangqs@163.com.

Abstract

Naringenin is a flavanone compound found in citrus fruits. Recent researches showed that naringenin has many potentially pharmacological effects. However, the therapeutic effect and the potential mechanism of naringenin on diabetic nephropathy (DN) remain to be elucidated. DN model was established by a high-fat diet combined with streptozotocin (STZ), which was confirmed by the levels of fasting blood glucose (FBG, more than 11.1 mmol/L) and urinary albumin (10 times higher than the normal mice). After 5 weeks of STZ injection, the DN was developed in model mice. Then naringenin (25 or 75 mg/kg·d) were supplemented for 4 weeks. At the end of the experiment, the injury of the renal function and structure was deteriorated. Concomitantly, peroxisome proliferators-activated receptors (PPARs) protein expression was down-regulated, and CYP4A expression and 20-hydroxyeicosatetraenoic acid (20-HETE) level were reduced in DN mice. Naringenin administration improved the renal damage of DN mice, and up-regulated PPARs expression, increased CYP4A-20-HETE level. Consistent with the results of in vivo, glucose at 30 mmol/L (high glucose, HG) significantly induced cell proliferation and hypertrophy in NRK-52E cells, following the reductive PPARs protein expression and the downward CYP4A-20-HETE level. Naringenin (0.01, 0.1, 1 μmol/L) reversed these changes induced by HG in a dose-dependent manner. HET0016, a selective inhibitor of 20-HETE synthase, partially blocked the effects of naringenin. In conclusion, naringenin has a therapeutic effect on DN, which may be, at least partly, related to the activation of CYP4A-20-HETE and the up-regulation of PPARs.

KEYWORDS:

20-HETE; CYP4A; Diabetic nephropathy; Naringenin; PPARs

PMID:
31063766
DOI:
10.1016/j.cbi.2019.05.004

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center