Abstract
Non-enzymatic glycation of DNA and the associated effects are among pathogenic factors in diabetes mellitus. Natural polyphenols have anti-diabetic activity. Herein, the protective role of one of the phytochemicals, rosmarinic acid (RA), was evaluated in glycation (with fructose) of human DNA and expression of Akt genes in the hippocampus of diabetic rats. In-vitro studies using fluorescence, agarose gel electrophoresis, fluorescence microscopy, and thermal denaturation analyses revealed that glycation causes DNA damage and that RA inhibits it. In-vivo studies were performed by induction of diabetes in rats using streptozotocin. The diabetic rats were given RA daily through gavage feeding. The expression of Akt genes (inhibitors of apoptosis) in the hippocampus was evaluated using RT-qPCR. In diabetic rats, Akt1 and Akt3 were significantly down-regulated compared to the control group. Treating the diabetic rats with RA returned the expression of Akt1 and Akt3 relatively to the normal condition. Past studies have shown that diabetes induces apoptosis in the hippocampal neurons. Given that glycation changes the genes expression and causes cell death, apoptosis of the hippocampal neurons can be due to the glycation of DNA. The results also suggest that RA has reliable potency against the gross modification of DNA under hyperglycemic conditions.
Highlights
Spontaneous glycation is a non-enzymatic process that occurs naturally under physiological conditions, but it is greatly intensified under hyperglycemic conditions and can be fatal
This study aimed to evaluate the extent of fructose-mediated Advanced Glycation End-products (AGEs) damage to DNA and its inhibition by the interference of Rosmarinic acid (RA), as well as evaluation of Akt genes expression in the hippocampus of diabetic rats treated with RA
The absorption spectroscopic analysis of the fructose-modified DNA showed a broad absorption band centered at 260 nm with marked hyperchromicity after 15 days of incubation; this was comparable to the native form (Fig. 1)
Summary
Spontaneous glycation is a non-enzymatic process that occurs naturally under physiological conditions, but it is greatly intensified under hyperglycemic conditions and can be fatal. Amino groups in nucleic acids can serve as a substrate for the non-enzymatic addition of reducing sugars, leading to some gross alteration in the DNA structure. Given DNA glycation with different reducing sugars and the possible association of this event with diabetes, the search for tarping agents with the capability of targeting any step of the glycation pathway has always been a health concern. Inhibition of glycation, both in vivo and in food, is vital for promoting human health, especially for the control of d iabetes[15]. We tried to explore the probable relationship between apoptosis of hippocampal neurons in diabetic conditions and DNA glycation
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