Evaluation of the Antidiabetic Potential of Extracts of Urtica dioica, Apium graveolens, and Zingiber officinale in Mice, Zebrafish, and Pancreatic β-Cell

Medicinal plants are commonly used in the treatment of diabetes, particularly as they contain flavonoids and phenolic compounds. The present study aims to investigate the activities of a polyherbal formulation made from Urtica dioica, Apium graveolens, and Zingiber officinale (UAZ) against streptozotocin–nicotinamide ((STZ-NA)-induced type 2 diabetes in CD1 mice, glucose-induced type 2 diabetes (T2DM) in zebrafish, and high glucose-induced damage in RINm5F pancreatic β-cells. In fasting mice, plasma glucose, glycosylated hemoglobin (HbA1C), lipid hydroperoxides (LOOH), thiobarbituric acid reactive substances (TBARS), and lipid profiles were significantly increased, whereas insulin, enzymatic antioxidants, and carbohydrate metabolic enzymes were altered significantly in diabetic mice. Zebrafish had similar glucose levels, liver enzymes, and lipid profiles compared to mice. The study investigated the effects of the extract in enhancing cell viability, insulin secretion, and reducing lipid peroxidation and intracellular reactive oxygen species (ROS) levels in RINm5F cells damaged by high glucose. All the above biochemical parameters were enhanced in both mice and zebrafish treated; the combined extract UAZ normalized all the biochemical parameters. The medicinal plant extracts, used either separately or in combination, ameliorated the adverse effect of glucose on cell viability and functionality of beta-RINm5F cells.

A Phenolic Fraction from Catharanthus roseus L. Stems Decreases Glycemia and Stimulates Insulin Secretion

Catharanthus roseus (L.) G. (C. roseus) is a medicinal plant used traditionally for diabetes mellitus control. Several compounds of an alkaloidal nature have been proposed as hypoglycemic principles. However, little attention has been paid to other compounds in this plant that could also participate in this hypoglycemic activity. This study aimed to analyze the hypoglycemic effect of a polyphenolic fraction from C. roseus, as well as its action on insulin secretion and expression in RINm5F cells. Methods. An alkaloid-free aqueous extract was obtained from C. roseus stems. The hypoglycemic effect of different doses of this extract was evaluated in normal and streptozotocin-induced diabetic mice. This extract was fractionated by bipartition, and the resultant fractions were assessed by their hypoglycemic effects. Subsequently, the fraction with the greater hypoglycemic activity was added to the RINm5F cells, and the expression and secretion of insulin were analyzed. The antioxidant activity was determined by the DPPH method and through chromatographic analysis of the most active fraction by HPLC, using an Econosphere C18 column. Results. The aqueous alkaloid-free extract of C. roseus stems significantly reduced blood glucose in normal and diabetic mice. The fractionation of this extract provided three fractions, one of which (a precipitate) showed significant reductions in glycemia at 6 h (48.1 and 64.5% in normal and diabetic mice, respectively). This precipitate contained phenolic compounds and saponins. Its chromatographic analysis showed that it is formed by several phenolic compounds; gallic acid (0.053%) and chlorogenic acid (0.216%) were identified and quantified. Conclusion. The phenolic fraction of C. roseus containing gallic acid and chlorogenic acid had a hypoglycemic effect that may be explained by an increase in insulin secretion.

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.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.Keywords: Apium graveolens, anti-glycation, polyphenols methylglyoxal, insulin, pancreatic cells