AMYs x DPP-4 x α-glucosidase

Diabetes, regarded as a prevalent metabolic disorder with multifactorial origins, contributes to a myriad of global complications. These cumulate an elevated susceptibility to kidney failure, nerve impairment, blindness, atherosclerosis, heart ailments, and even strokes. Recent investigations underscore the diverse roles of associated biomarkers in diabetes progression. Among these are biomarkers for diabetes mellitus such as DPP-4, PPAR-ϒ, SGLT-2, α-amylase, and α-glucosidase, which are linked to the onset of diabetes and its related problems. As a result of undesirable adverse consequences linked to extant synthetic antidiabetic medications, research attention is increasingly directed towards formulating natural antidiabetic drugs, aiming for enhanced efficacy and reduced complications. Cyanobacteria stand out as a pivotal repository of natural bioactive metabolites extensively harnessed for pharmaceutical and nutraceutical development. The potent bioactive compounds sourced from cyanobacteria hold substantial promise, kindling high expectations in scientific research and presenting vast prospects for drug discovery and advancement. Some of these bioactive compounds have demonstrated impressive effectiveness, displaying successful applications across various phases of clinical trials. This review strives to provide a more precise understanding of diabetes mellitus, encompassing its clinical manifestation, epidemiological data, complications, and prevailing treatment modalities. The objective of this review is to contribute researchers and readers an enhanced and accurate understanding of diabetes mellitus by covering its clinical manifestation, epidemiological evidence, difficulties, and prevailing therapeutics possibilities.

In this research, the therapeutic potential of cichoriin is examined, and for the first time, its antioxidant, hemocompatible, and cardioprotective properties against oxidative stress caused by H₂O₂ in H9c2 cardiac cells are reported. At 100 μg/mL, cichoriin exhibited potent in vitro activities, including DPPH radical scavenging (80.71 ± 0.33 %), metal chelation (74.60 ± 0.39 %), anti-lipid peroxidation (87.96 ± 1.01 %), and pancreatic lipase inhibition (84.88 ± 0.53 %). The IC₅₀ for hemolysis test was 1211.37 μg/mL, indicating limited toxicity towards RBCs. In the MTT assay, cichoriin demonstrated minimal cytotoxicity toward 3T3-L1 and H9c2 cells, maintaining cell viability at 65.22 ± 0.2 % and 67.40 ± 0.82 %, respectively, at 100 μg/mL. Glucose uptake in yeast was significantly enhanced by 81.35 ± 0.53 % at 100 μg/mL with glucose (20 mM), alongside delayed glucose diffusion and inhibition of α-amylase (74.55 ± 0.46 %), α-glucosidase (84.08 ± 0.57 %), and DPP-IV (77.78 ± 0.67 %). Cell viability assay and DCFH-DA staining revealed that cichoriin preserved cellular integrity under oxidative stress in H9c2 cells. It restored the SOD and CAT activities while reducing lipid peroxidation and LDH release induced by H₂O₂. In-silico studies, including molecular docking, ADMET, and ProTox analyses, confirmed strong binding affinities to target proteins, favorable drug-likeness, and a low toxicity profile. Overall, cichoriin exhibits potent antidiabetic and cardioprotective properties, supporting its potential development as a natural lead compound for the treatment of diabetes-associated cardiovascular disorders.

Type 2 diabetes mellitus (T2DM) is a global health burden, with hyperglycemia as the main hallmark. This review commences with a concise overview of the intricate mechanisms underlying glucose uptake and utilization in organisms. Notably, we emphasize that T2DM management strategies pivot on delaying carbohydrate digestion, augmenting insulin secretion, and enhancing insulin sensitivity in target tissues. Unfortunately, the drugs currently available in the market for the treatment of T2DM have unpleasant side effects, spurring an urgent quest for safer and more efficacious alternatives. Flavonoids, emerging as a promising class of bioactive compounds derived from plants, offer a multi-faceted approach to diabetes treatment. Specifically, they potently inhibit enzymes such as α-amylase, α-glucosidase, dipeptidyl peptidase-4 (DPP-4), glycogen phosphorylase (GP) and protein-tyrosine phosphatase-1B (PTP1B). Through an in-depth analysis, this review not only summarizes these inhibitory actions but also establishes the structure-activity relationship (SAR), providing a blueprint for rational drug design. However, the clinical translation of flavonoids has been hampered by their suboptimal water solubility and bioavailability, attributable to the characteristic carbonyl and hydroxyl groups. Ingeniously, this chemical quirk has been harnessed to engineer metal chelates, which exhibit enhanced pharmacokinetic profiles. Herein, we offer an exhaustive overview of the latest advancements in flavonoid metal complexes research, spotlighting their potential as next-generation diabetes therapeutics. Available data are poised to galvanize the development of novel flavonoid derivatives, be it as potent drugs or functional foods, for combating T2DM.