Effect of berberine on methylglyoxal-induced endothelial dysfunction in rats: The role of AMPK/PI3K/AKT/ENOS pathway

Objective: There are many data on the beneficial effects of berberine on the cardiovascular system. The aim of this study is to investigate the protective effect of berberine on methyglyoxal (MGO)- induced endothelial dysfunction in rats and the role of AMPK/PI3K/AKT/eNOS pathway in this effect. Method: A total of 48 male rats were used in our study. The rats were divided into 4 groups as control, those exposed to MGO, rats treated with MGO together with berberine and rats treated with berberine alone. MGO was administered to rats in the MGO group with an osmotic pump to the dorsal region for 4 weeks. In the.MGO berberine group rats berberine was applied through gavage a single dosage a day with MGO osmotic pump application. In the last group, only berberine was administered by oral gavage. After 4 weeks, the thoracic aorta of the rats was removed. Acetylcholine (ACh), sodium nitroprusside (SNP), potassium chloride (KCl) and phenylephrine (Phe) responses were obtained in the isolated organ bath. In addition, ACh responses were obtained after incubation of L-NAME, ODQ, Wortmannin and Compound C. Results: While MGO administration caused a significant decrease in ACh-induced endothelialdependent responses, a significant increase was obtained in these responses in the MGO berberine group. No significant difference was observed between the groups in endothelialindependent SNP responses. No significant difference was observed between the groups in both Fe and KCl contractions. A decrease in ACh responses was obtained with L-NAME, ODQ, Wortmannin incubation, while Compound C incubation did not affect this response. Conclusion: it was concluded that MGO impairs endothelial-dependent relaxation responses and berberine provides an improvement in endothelial function by creating a significant increase in this response. Berberine may exert this protective effect through the NOS and PI3K/Akt pathway. Key Words: Endothelium, Berberine, Methylglyoxal