Natural food products have been used for combating human diseases for thousands of years. Naturally occurring flavonoids including flavones, flavonols, flavanones, flavonols, isoflavones and anthocyanidins have been proposed as effective supplements for management and prevention of diabetes and its long-term complications based on in vitro and animal models. To summarize the roles of dietary flavonoids in diabetes management and their molecular mechanisms. Tremendous studies have found that flavonoids originated from foods could improve glucose metabolism, lipid profile, regulating the hormones and enzymes in human body, further protecting human being from diseases like obesity, diabetes and their complications. In the current review, we summarize recent progress in understanding the biological action, mechanism and therapeutic potential of the dietary flavonoids and its subsequent clinical outcomes in the field of drug discovery in management of diabetes mellitus.

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Antidiabetic properties of dietary flavonoids: a cellular mechanism review

Diabetes mellitus (DM) is a prevailing global health metabolic disorder, with an alarming incidence rate and a huge burden on health care providers. DM is characterized by the elevation of blood glucose due either to a defect in insulin synthesis, secretion, binding to receptor, or an increase of insulin resistance. The internal and external factors such as obesity, urbanizations, and genetic mutations could increase the risk of developing DM. Flavonoids are phenolic compounds existing as secondary metabolites in fruits and vegetables as well as fungi. Their structure consists of 15 carbon skeletons and two aromatic rings (A and B) connected by three carbon chains. Flavonoids are furtherly classified into 6 subclasses: flavonols, flavones, flavanones, isoflavones, flavanols, and anthocyanidins. Naturally occurring flavonoids possess anti-diabetic effects. As in vitro and animal model’s studies demonstrate, they have the ability to prevent diabetes and its complications. The aim of this review is to summarize the current knowledge addressing the antidiabetic effects of dietary flavonoids and their underlying molecular mechanisms on selected pathways: Glucose transporter, hepatic enzymes, tyrosine kinase inhibitor, AMPK, PPAR, and NF-κB. Flavonoids improve the pathogenesis of diabetes and its complications through the regulation of glucose metabolism, hepatic enzymes activities, and a lipid profile. Most studies illustrate a positive role of specific dietary flavonoids on diabetes, but the mechanisms of action and the side effects need more clarification. Overall, more research is needed to provide a better understanding of the mechanisms of diabetes treatment using flavonoids.

https://www.mdpi.com/2218-273X/9/9/430/pdf

Flavonoids and Their Anti-Diabetic Effects: Cellular Mechanisms and Effects to Improve Blood Sugar Levels

α-Glucosidase inhibitors are described as the most effective in reducing post-prandial hyperglycaemia (PPHG) from all available anti-diabetic drugs used in the management of type 2 diabetes mellitus. As flavonoids are promising modulators of this enzyme’s activity, a panel of 44 flavonoids, organised in five groups, was screened for their inhibitory activity of α-glucosidase, based on in vitro structure–activity relationship studies. Inhibitory kinetic analysis and molecular docking calculations were also applied for selected compounds. A flavonoid with two catechol groups in A- and B-rings, together with a 3-OH group at C-ring, was the most active, presenting an IC50 much lower than the one found for the most widely prescribed α-glucosidase inhibitor, acarbose. The present work suggests that several of the studied flavonoids have the potential to be used as alternatives for the regulation of PPHG.

α-Glucosidase inhibition by flavonoids: an in vitro and in silico structure-activity relationship study.

Inhibitory kinetics and mechanism of kaempferol on α-glucosidase

Pharmacokinetic, pharmacodynamic and formulations aspects of Naringenin: An update.

Naringenin inhibits α-glucosidase activity: A promising strategy for the regulation of postprandial hyperglycemia in high fat diet fed streptozotocin induced diabetic rats

Antigen encounter directs CD4+ T cells to differentiate into T helper or regulatory cells. This process focuses the immune response on the invading pathogen and limits tissue damage. Mechanisms that govern T helper cell versus T regulatory cell fate remain poorly understood. Here, we show that the E3 ubiquitin ligase Cul5 determines fate selection in CD4+ T cells by regulating IL-4 receptor signaling. Mice lacking Cul5 in T cells develop Th2 and Th9 inflammation and show pathophysiological features of atopic asthma. Following T cell activation, Cul5 forms a complex with CIS and pJak1. Cul5 deletion reduces ubiquitination and subsequent degradation of pJak1, leading to an increase in pJak1 and pSTAT6 levels and reducing the threshold of IL-4 receptor signaling. As a consequence, Cul5 deficient CD4+ T cells deviate from Treg to Th9 differentiation in low IL-4 conditions. These data support the notion that Cul5 promotes a tolerogenic T cell fate choice and reduces susceptibility to allergic asthma. 

/pdf/the-ubiquitin-ligase-cul5-regulates-cd4-t-cell-fate-choice-1il6pk5t.pdf

Aishwarya Suresh

Papers

Naringenin inhibits α-glucosidase activity: A promising strategy for the regulation of postprandial hyperglycemia in high fat diet fed streptozotocin induced diabetic rats

The ubiquitin ligase Cul5 regulates CD4+ T cell fate choice and allergic inflammation

Beyond Competency: A Student Perspective on Growth Through Clerkship Feedback.

Use of biologics for treatment of autoimmune inner ear disease.