Endocrinol Metab.  2021 Aug;36(4):810-822. 10.3803/EnM.2021.988.

Tetrahydrocurcumin Ameliorates Kidney Injury and High Systolic Blood Pressure in High-Fat Diet-Induced Type 2 Diabetic Mice

Affiliations
  • 1Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
  • 2Department of Physiology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
  • 3Cardiovascular Research Group, Khon Kaen University, Khon Kaen, Thailand
  • 4Institution of Genetic Cohort, Yonsei University Wonju College of Medicine, Wonju, Korea
  • 5Astrogen Inc., Daegu, Korea
  • 6Department of Internal Medicine and Institute of Tissue Regeneration, BK21 FOUR Project, Soonchunhyang University College of Medicine, Cheonan, Korea

Abstract

Background
Activation of the intrarenal renin-angiotensin system (RAS) is implicated in the pathogenesis of kidney injury and hypertension. We aimed to investigate the protective effect of tetrahydrocurcumin (THU) on intrarenal RAS expression, kidney injury, and systolic blood pressure (SBP) in high-fat diet (HFD)-induced type 2 diabetic mice.
Methods
Eight-week-old male mice were fed a regular diet (RD) or HFD for 12 weeks, and THU (50 or 100 mg/kg/day) was intragastrically administered with HFD. Physiological and metabolic changes were monitored and the expression of RAS components and markers of kidney injury were assessed.
Results
HFD-fed mice exhibited hyperglycemia, insulin resistance, and dyslipidemia compared to those in the RD group (P<0.05). Kidney injury in these mice was indicated by an increase in the ratio of albumin to creatinine, glomerular hypertrophy, and the effacement of podocyte foot processes. Expression of intrarenal angiotensin-converting enzyme, angiotensin II type I receptor, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-4, and monocyte chemoattractant protein-1 was also markedly increased in HFD-fed mice. HFD-fed mice exhibited elevated SBP that was accompanied by an increase in the wall thickness and vascular cross-sectional area (P<0.05), 12 weeks post-HFD consumption. Treatment with THU (100 mg/kg/day) suppressed intrarenal RAS activation, improved insulin sensitivity, and reduced SBP, thus, attenuating kidney injury in these mice.
Conclusion
THU alleviated kidney injury in mice with HFD-induced type 2 diabetes, possibly by blunting the activation of the intrarenal RAS/nicotinamide adenine dinucleotide phosphate oxidase IV (NOX4)/monocyte chemoattractant protein 1 (MCP-1) axis and by lowering the high SBP.

Keyword

Diabetic nephropathies; Renin-angiotensin system; Hypertension; Tetrahydrocurcumin; Curcumin
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