Polyphenols of leaves of Apium graveolens inhibit in vitro protein glycation and protect RINm5F cells against methylglyoxal-induced cytotoxicity

Background: The health benefits of edible plants have been widely investigated and disseminated. However, only polyphenols have been found to have sufficient therapeutic potential to be considered in clinical trials. Fewer manuscripts have other applications such as prospective health benefits and disease treatment. Other components of edible plants are responsible for a range of other benefits including antimalarial, burns, flu, cancer, inflammation, diabetes, glycation, antimicrobial, prevention of neurodegeneration, analgesic, antimigraine activity, sedative activities, etc. Accordingly, the public needs to be informed of the potential edible plants have to act on different targets and maintain better control over diabetes compared to commercial drugs which can be toxic, have side effects, do not have the capacity to maintain blood glucose at normal levels, and do not protect the patient from the complications of diabetes over time. Consequently, edible plants, such as Apium graveolen, which have therapeutic targets on AGEs formation, are potentially a better alternative treatment for diabetes. Aim: To demonstrate if CM is capable of suppressing the formation of AGEs and protein oxidation in vitro. Also to investigate if A. graveolens is a potential functional food that can be used to prevent the development of diabetic complications. Methods: The leaves of celery were extracted with methanol (CM). Polyphenols contents in CM were investigated by liquid chromatography-electrospray ionization mass. The ability of the compounds to inhibit formation of AGEs was evaluated in vitro models using formation of AGE fluorescence intensity, level of fructosamine, Nϵ-(carboxymethyl)lysine (CML), methylglyoxal (MG)-derived protein, and formation of amyloid cross β structure. Protein-oxidation was determined by thiol group and protein carbonyl content. Inhibition of MG-derived AGEs and MG-trapping ability were also measured. Additionally, insulin production was determined in methylglyoxal-treated pancreatic RINm5F cells assay. Results: Apigenin, kaempferol, apiin, rutin, caffeic acid, ferulic acid, chlorogenic acid, coumaroylquinic acid, and p-coumaric acid were the major polyphenols contained in CM. In all the model tests CM displayed potent AGE inhibitory activity, suggesting that CM delayed the three stages of glycation. Accordingly, the mechanisms of action of celery involving dicarbonyl trapping and breaking the crosslink structure in the AGEs formed may contribute to the protection of pancreatic RINm5F cells against MG conditions. Conclusion: These findings indicate that CM have an excellent anti-glycation effect which may be beneficial for future development of antiglycating agents for the treatment of diabetes.