SYNTHESIS OF CR(III)-ASPARTATE AND CU(II)-ASPARTATE COMPLEXES AS ANTIDIABETIC COMPOUND

The synthesis of Cr(III)-Aspartate and Cu(II)-Aspartate complexes has been successfully conducted by reacting CrCl3·6H2O and CuCl2·2H2O metals with aspartic acid. Therefore, this study aimed to synthesize Cr(Asp)2Cl2 and Cu(Asp)Cl2 as well as test their antidiabetic effects. The synthesis results of Cr(Asp)2Cl2 and Cu(Asp)Cl2 in the form of light purple and blue solids were 0.3001 g and 0.3095g with a yield of 95.14% and 95.02%, respectively. Furthermore, the antidiabetic test used 27 male mice (Mus musculus) with nine treatments for 21 days. The data obtained were analyzed statistically using analysis of variance, and the antidiabetic activity was expressed in percent glucose lowering. The result showed a decrease in blood glucose levels in mice after alloxan induction, with percent glucose lowering (%GL) values of 74.1874% for Cr(Asp)2Cl2 and 76.1337% for Cu(Asp)Cl2 compounds. Therefore, the Cr(Asp)2Cl2 and Cu(Asp)Cl2 compounds can be used as antidiabetic in mice which are also potentially used as metal-based drugs for the treatment of DM.

Amelioration of altered adipokines expression and serine/threonine phosphorylation of IRS1 in alloxan-induced diabetes by Potentilla fulgens and its phytochemical constituents

The present study is aimed at investigating the modulation of serine/threonine phosphorylation of IRS1 and the gene expression oftotal IRS1 and adipokines including TNF-α, IL-6 and adiponectin by the plant Potentilla fulgens and its phytochemical constituents catechin and (-)-epicatechin. Alloxan-induced diabetic mice with a two-to three-fold increase in their blood glucose levels were taken for the study. The level of protein expression of total (tIRS1), tyrosine (pIRS1), and serine phosphorylated IRS1 (pIRS1 ser307) was analysed by western blot, and the gene expression level of tIRS1, IL-6, TNF-α, and adiponectin was analysed by real-time PCR. Since evidences strongly suggest that adiponectin, TNF-α, and IL-6 are implicated in insulin resistance and type 2 diabetes, therefore these three adipokines have been targeted in our study with an aim to investigate the anti-inflammatory and antidiabetic effects of our plant Potentillafulgens(PF) andits phytochemicals. The results strongly demonstrates the capability of PF and its phytochemicals to modulate the ser/thr phosphorylation state of IRS1 by downregulating the serine 307 phosphorylation while simultaneously upregulating the tyrosine phosphorylation of IRS1. The results also indicate the ability of the same to alleviate inflammation in alloxan induced diabetes by modulating the expression of the insulin sensitizing hormone adiponectin and the pro-inflammatory cytokines L-6 and TNF-α.

Mechanisms Underlying the Antidiabetic Activities of Polyphenolic Compounds: A Review

Polyphenolic compounds are thought to show considerable promise for the treatment of various metabolic disorders, including type 2 diabetes mellitus (T2DM). This review addresses evidence from in vitro, in vivo, and clinical studies for the antidiabetic effects of certain polyphenolic compounds. We focus on the role of cytotoxic human amylin (hA) aggregates in the pathogenesis of T2DM, and how polyphenols can ameliorate this process by suppressing or modifying their formation. Small, soluble amylin oligomers elicit cytotoxicity in pancreatic islet β-cells and may thus cause β-cell disruption in T2DM. Amylin oligomers may also contribute to oxidative stress and inflammation that lead to the triggering of β-cell apoptosis. Polyphenols may exert antidiabetic effects via their ability to inhibit hA aggregation, and to modulate oxidative stress, inflammation, and other pathways that are β-cell-protective or insulin-sensitizing. There is evidence that their ability to inhibit and destabilize self-assembly by hA requires aromatic molecular structures that bind to misfolding monomers or oligomers, coupled with adjacent hydroxyl groups present on single phenyl rings. Thus, these multifunctional compounds have the potential to be effective against the pleiotropic mechanisms of T2DM. However, substantial further research will be required before it can be determined whether a polyphenol-based molecular entity can be used as a therapeutic for type 2 diabetes.

Ginsenoside Re, Produces Multi-targeted Potent Antidiabetic Effects Via Estrogen Receptor Signaling Pathway in Rat, an Alternative Multi-Targeted Therapeutic for Type 2 Diabetes

Aims: To identify more effective ginsenoside for type 2 diabetes (T2D) and clarify whether the ginsenoside characterizing estrogenic multi-targeted antidiabetic effects. Study Design: Identifying more effective ginsenoside through preclinical evaluation of antidiabetic effects of representative ginsenosides with T2D rat model, and further test pharmacological mechanism underlying the potent antidiabetic effects of the ginsenoside in the same model. Place and Duration of Study: Key laboratory for Pharmacy, Inner Mongolia Medical University, March 2018 to November 2020. Methodology: Used a total of 240 female adult rats. Rat model of T2D induced by high-fat diet fed and streptozotocin. Five tapes of representative ginsenosides (Rb1, Rd, Rg3, Re, Rg1) administrated at low (20 mg/kg daily) and high (40 mg/ kg daily) doses to T2D rats with orally for 4 weeks. Detect testing indexes with biochemical, histological, Quantitative Real-Time PCR, and western blots analysis. Results: Ginsenoside Re (Re), very significantly lowered blood glucose (P<0.01), lipids (P<0.001), free fatty acid (P<0.001), and glucagon (P<0.01) levels, markedly improved impaired insulin sensitivity (P<0.01), ameliorated oxidative stress (P<0.01) and inflammation (P<0.01) in T2D rats, exhibited potent antidiabetic effects. Moreover, Re, phosphorylate serine/threonine kinase (Akt) (P<0.01) and endothelial nitric oxide synthase (eNOS) (P<0.01), up regulates B-cell lymphoma-2 (P<0.01) and insulin gene expression (P<0.01), down regulates glucagon gene expression(P<0.01), reverse impaired glucagon-like peptide 1 (P<0.01); exhibits multi-targeted effects; these effects of Re were inhibited by estrogen receptor (ER) inhibitor (ICI-182,780) (P<0.01). Functionally, the antidiabetic effects of Re were sequentially inhibited by inhibitor of ER, Akt, and eNOS, respectively (P<0.01). Conclusion: These findings, revealed a novel pharmacological property of Re that characterized in multi-targeted potent antidiabetic effects mediated by ER/Akt/eNOS/NO signaling pathway, provide the first evidence for the potential use of Re, as a multi-targeted therapeutic for T2D, particularly, a novel candidate for replacement of estrogen therapy and NO therapy in diabetes.

Histopathological Profiles of Rats (Rattus norvegicus) Induced with Streptozotocin and Treated with Aqueous Root Extracts of Ruellia tuberosa L.

Diabetes mellitus (DM) is a serious worldwide health threat since the number of people with DM is forecasted to grow annually. Thus, effective and affordable treatment is urgently needed. Our previous studies used n-hexane and hydroethanolic root extracts of Ruellia tuberosa L. which significantly affected diabetic rats. In this study, aqueous R. tuberosa L. root extracts were used as treatments for the diabetic rat model and their effects were evaluated. Diabetes was generated by the administration of streptozotocin (STZ) at 20 mg/kg within 5 sequential days. Male Wistar rats were orally treated with the extracts and standard drug (metformin 200 mg/kg) and vehicle every day for 4 weeks. Hypoglycemic effects were assessed for normal, diabetic control, standard, and extract-treated groups. Histopathology was also carried out for the pancreatic, hepatic, and kidney tissues. The progression of diabetes was considerably diminished after extract treatment. In treated rats, the highest dose of extract induced a decline in blood glucose and serum malondialdehyde (MDA) levels at 25% and 35%, respectively. Furthermore, aqueous extract of R. tuberosa L. treatment decreased MDA levels in the pancreas by 12%. Histologic examination of the organ tissues of diabetic rats showed deteriorating alterations. After treatment, histopathological damages to the tissues and cells were reversed. The results of the experiments recommend that aqueous extract of R. tuberosa L. has antidiabetic effects on STZ-induced diabetic rats; nevertheless, a higher dose of the aqueous extracts is needed to achieve more significant results.