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Phytomedicine. 2018 Mar 1;41:45-53. doi: 10.1016/j.phymed.2018.01.026. Epub 2018 Jan 31.

Kidney protection effects of dihydroquercetin on diabetic nephropathy through suppressing ROS and NLRP3 inflammasome.

Author information

1
Department of Nephrology, Changhai Hospital, Second Military Medical University, Shanghai 200433, PR China.
2
Department of Microbiological and Biochemical Pharmacy & Key Lab of Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University, Shanghai 201203, PR China.
3
Department of Cardiology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, PR China.
4
Department of Microbiological and Biochemical Pharmacy & Key Lab of Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University, Shanghai 201203, PR China. Electronic address: dianwenju@fudan.edu.cn.
5
Department of Nephrology, Changhai Hospital, Second Military Medical University, Shanghai 200433, PR China. Electronic address: meixiaobin@smmu.edu.cn.

Abstract

BACKGROUND:

Diabetic nephropathy (DN), the leading cause of end-stage renal disease, is acknowledged as an independent risk factor for cardiovascular disease, which underlines the urgent need for new medications to DN. Dihydroquercetin (DHQ), an important natural dihydroflavone, exerts significant antioxidant, anti-inflammatory, and antifibrotic properties, but its effects on DN have not been investigated yet.

PURPOSE:

We aimed to explore the kidney protection effects of DHQ on DN rats induced by high-fat diet/streptozotocin in vivo and the underlying mechanisms of DHQ on renal cells including HBZY-1 and HK2 exposed to high glucose in vitro.

METHODS:

Major biochemical indexes were measured including urine microalbumin, fasting serum glucose, serum levels of creatinine, total cholesterol and low density lipoprotein cholesterol. Renal histologic sections were stained with hematoxylin-eosin, periodic acid-Schiff and Masson. The cell proliferation was assessed by MTT assay. Reactive oxygen species (ROS) generation was detected by DCFH-DA assay and laser scanning confocal microscope. Expression of all proteins was examined by western-blot.

RESULTS:

In high-fat diet/streptozotocin-induced DN rats, DHQ at the dose of 100 mg/kg/day significantly attenuated the increasing urine microalbumin excretion, hyperglycemia and lipid metabolism disorders, and mitigated renal histopathological lesions. In in vitro studies, DHQ significantly suppressed cell proliferation and the excessive ROS generation, and alleviated the activation of nucleotide binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome and the expression of renal fibrosis-associated proteins in renal cells exposed to high glucose.

CONCLUSION:

The results revealed that DHQ possesses kidney protection effects including attenuating urine microalbumin excretion, hyperglycemia and lipid metabolism disorders, and mitigating renal histopathological lesions on DN, and one of the possible renal-protective mechanisms is suppressing ROS and NLRP3 inflammasome.

KEYWORDS:

Diabetic nephropathy; Dihydroquercetin; Extracellular matrix; NLRP3 inflammasome; ROS

PMID:
29519318
DOI:
10.1016/j.phymed.2018.01.026
[Indexed for MEDLINE]
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