Nutrition Research and Practice

  • 제17권3호
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  • Pages.421-437
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  • 2023
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  • 1976-1457(pISSN)
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  • 2005-6168(eISSN)
한국영양학회 (The Korean Nutrition Society)
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Highly water-soluble diacetyl chrysin ameliorates diabetes-associated renal fibrosis and retinal microvascular abnormality in db/db mice

  • Young-Hee Kang (Department of Food and Nutrition and Nutrition and Korean Institute of Nutrition, Hallym University) ;
  • Sin-Hye Park (Department of Food and Nutrition and Nutrition and Korean Institute of Nutrition, Hallym University) ;
  • Young Eun Sim (Department of Food and Nutrition and Nutrition and Korean Institute of Nutrition, Hallym University) ;
  • Moon-Sik Oh (Department of Food and Nutrition and Nutrition and Korean Institute of Nutrition, Hallym University) ;
  • Hong Won Suh (Department of Pharmacology, College of Medicine, Hallym University) ;
  • Jae-Yong Lee (FrontBio Inc.) ;
  • Soon Sung Lim (Department of Food and Nutrition and Nutrition and Korean Institute of Nutrition, Hallym University)
  • 투고 : 2022.06.14
  • 심사 : 2022.09.20
  • 발행 : 2023.06.01
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초록

BACKGROUND/OBJECTIVES: Chronic or intermittent hyperglycemia is associated with the development of diabetic complications. Oxidative stress and inflammation can be altered by hyperglycemia in diverse tissues, including kidneys and eyes, and play a pivotal role in diabetic complications. Our previous studies showed that the water-insoluble 5,7-dihydroxyflvone chrysin effectively combats diabetic damages incurred in diabetic kidneys and retinas. The current study employed the newly-synthesized 5.7-di-O-acetylchrysin, having higher solubility than chrysin, to compare the effects on diabetes-associated renal fibrosis and abnormal retinal neovascularization. MATERIALS/METHODS: In the in vivo study, db/db mice as animal models of type 2 diabetes were orally administrated 10 mg/kg BW diacetylchrysin, daily for 10 weeks. RESULTS: Unlike chrysin, oral administration of 10 mg/kg diacetylchrysin did not lower the blood glucose level and 24 h urine volume in db/db mice. Nevertheless, the urinary albumin excretion was markedly reduced. The administration of diacetylchrysin also diminished the deposition of collagen fibers in diabetic glomeruli and tubules by suppressing the induction of connective tissue growth factor and collagen IV in diabetic kidneys. Supplying diacetylchrysin enhanced the membrane type-1 matrix metalloproteinase (MMP) expression reduced in diabetic kidneys, while the tissue inhibitor of MMP-2 induction was attenuated in diacetylchrysin-challenged diabetic kidneys. In addition, supplementing diacetylchrysin to diabetic mice ameliorated renal injury due to glomerulosclerosis and tubular interstitial fibrosis. Furthermore, the reduced retinal inductions of Zonula occludens-1 and vascular endothelial cadherin in db/db mice were elevated in the retinal tissues of diacetylchrysin-treated animals. Oral administration of diacetylchrysin curtailed the induction of vascular endothelial growth factor (VEGF) and VEGF receptor 2 in db/db mice, ultimately retarding diabetes-associated retinal neovascularization. Additionally, the retinal formation of acellular capillaries with leaky vessels was reduced in diacetylchrysin-treated db/db mice. CONCLUSION: Diacetylchrysin may act as a potent pro-health agent for treating renal fibrosis-associated diabetic nephropathy and retinal neovascularization-associated diabetic retinopathy.

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과제정보

This research was financially supported by FrontBio Inc. and the Basic Science Research Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Education (2021R1A6A1A03044501).

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