Chrysin ameliorates podocyte injury and slit diaphragm protein loss via inhibition of the PERK-eIF2α-ATF-CHOP pathway in diabetic mice

Acta Pharmacologica Sinica
Min-Kyung KangYoung-Hee Kang

Abstract

Glomerular epithelial podocytes are highly specialized cells that play a crucial role in maintaining normal function of the glomerular filtration barrier via their foot processes. Chrysin (5,7-dihydroxyflavone) is a natural flavonoid found in propolis and mushrooms that has anti-inflammatory, antioxidant and anticancer properties. This study aimed to evaluate the renoprotective effects of chrysin on podocyte apoptotic loss and slit diaphragm protein deficiency in high glucose-exposed podocytes and in db/db mouse kidneys. Exposure to high glucose (33 mmol/L) caused glomerular podocyte apoptosis in vitro, which was dose-dependently attenuated by nontoxic chrysin (1-20 μmol/L) through reduction of DNA fragmentation. Chrysin treatment dose-dependently restored the increased Bax/Bcl-2 ratio, and suppressed Apaf-1 induction and the elevated cytochrome c release in high glucose-exposed renal podocytes. In diabetic db/db mice, oral administration of chrysin (10 mg·kg-1·d-1, for 10 weeks) significantly attenuated proteinuria, and alleviated the abnormal alterations in glomerular ultrastructure, characterized by apoptotic podocytes and foot process effacement. In addition, this compound improved the induction of slit diaphragm proteins p...Continue Reading

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Citations

Dec 7, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Hiroshi Kitamura
Jan 12, 2019·European Journal of Nutrition·Nelson AndradeFátima Martel
Mar 28, 2019·Journal of Cellular Physiology·Tahereh FarkhondehBabak Roshanravan
Jan 16, 2021·Biochemical and Biophysical Research Communications·Guangrong HuHui Sun
Mar 7, 2021·Molecular and Cellular Endocrinology·Yanhong WangRongshan Li
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Sep 5, 2021·Journal of the American Society of Nephrology : JASN·Khurrum ShahzadBerend Isermann

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