Reno-protective Effects of Coreopsis Tinctoria Flavonoids in db/db Mice Models Through the AGE/RAGE Pathway

Abstract

Introduction. The study investigates the renal protective effects 
of flavonoids derived from Coreopsis tinctoria Nutt in type 2 
diabetes using db/db mice. 
Methods. With the db/m mice born in the same litter as the 
non-diabetic normal group, 8-week-old db/db mice were divided 
into four groups: a diabetes model group, a low-dose (0.4 g/kg) 
flavonoids group, a high-dose (1.2 g/kg) flavonoids group, and 
a metformin positive control group. Mice were treated daily for 
8 weeks. 
Results. After 8 weeks of continuous gavage feeding, the high-dose 
group of flavonoids significantly improved fasting blood glucose 
levels in 16-week-old db/db mice, and both dosages of flavonoids 
reduced average daily water intake. The levels of serum creatinine 
(CRE) and BUN in db/db diabetic mice were significantly reduced 
by both high and low dosages of flavonoids, mitigating the loss 
of glomerular cells under hyperglycemic conditions, inhibiting 
glomerular hypertrophy and mesangial matrix hyperplasia, and 
demonstrating protective effects on renal function damage. The 
levels of AGEs in db/db mice kidneys were elevated compared to 
db/m mice, but significantly decreased with flavonoid treatment. 
Flavonoids also reduced RAGE protein expression and NF-κB 
activation. Additionally, both doses of flavonoids lowered MDA 
and IL-1β levels, and enhanced antioxidant enzyme activities. 
Conclusions. The study concludes that flavonoids from Coreopsis 
tinctoria Nutt can inhibit the accumulation of AGEs and binding 
to RAGE in kidneys, improve oxidative stress and inflammation, 
and protect against renal damage induced by hyperglycemia. 
This suggests their potential of flavonoids from Coreopsis tinctoria 
Nutt as functional food and medicine for diabetic nephropatthy.