The Coming Age of Flavonoids in the Treatment of Diabetic Complications

Abstract

Diabetes mellitus (DM), and its micro and macrovascular complications, is one of the biggest challenges for world public health. Despite overall improvement in prevention, diagnosis and treatment, its incidence is expected to continue increasing over the next years. Nowadays, finding therapies to prevent or retard the progression of diabetic complications remains an unmet need due to the complexity of mechanisms involved, which include inflammation, oxidative stress and angiogenesis, among others. Flavonoids are natural antioxidant compounds that have been shown to possess anti-diabetic properties. Moreover, increasing scientific evidence has demonstrated their potential anti-inflammatory and anti-oxidant effects. Consequently, the use of these compounds as anti-diabetic drugs has generated growing interest, as is reflected in the numerous in vitro and in vivo studies related to this field. Therefore, the aim of this review is to assess the recent pre-clinical and clinical research about the potential effect of flavonoids in the amelioration of diabetic complications. In brief, we provide updated information concerning the discrepancy between the numerous experimental studies supporting the efficacy of flavonoids on diabetic complications and the lack of appropriate and well-designed clinical trials. Due to the well-described beneficial effects on different mechanisms involved in diabetic complications, the excellent tolerability and low cost, future randomized controlled studies with compounds that have adequate bioavailability should be evaluated as add-on therapy on well-established anti-diabetic drugs.

Effect of Hesperetin Treatment on Blood Glucose Level, Spermatozoa Quality, and Spermatozoa Quantity in Alloxan-Induced Diabetic Mice

“…In the eighth week, antidiabetic effects of hesperetin at all doses were not significantly different from the normal control group. Flavonoid acted as an active antidiabetic compound triggered insulin production and reduced blood glucose levels (Al-Ishaq et al, 2019;Caro-Ordieres et al, 2020).…”

Lipotoxicity and Diabetic Nephropathy: Novel Mechanistic Insights and Therapeutic Opportunities

“…Polyphenols, flavonoids, and food rich-flavonoids also present lipid-lowering properties that could ameliorate lipotoxicity in diabetic kidney disease [241]. Recently, a study performed by Jayachandran et al demonstrated the capacity of isoquecertin to regulate lipid metabolism via AMPK pathway [196].…”

Metabolic Impact of Flavonoids Consumption in Obesity: From Central to Peripheral

“…Flavonoids are abundant in food and beverages highly consumed by human population including fruits, vegetables, tea, cocoa or wine [ 42 ] and in global are the bioactive compounds more largely associated with a reduced risk of all-cause mortality, type 2 diabetes [ 43 , 44 , 45 , 46 ], CVD [ 36 , 47 ], obesity and its comorbidities such as non-alcoholic fatty liver disease (NAFLD) [ 48 , 49 , 50 ] and more recently they have been described as potential therapeutic agents against cognitive pathologies such as Alzheimer’s disease (AD) [ 42 , 51 , 52 ] or cerebrovascular alterations [ 47 ].…”

“…As other groups of flavonoids, flavonols have shown healthy effects. They exhibit anticarcinogenic, anti-inflammatory, and antioxidant activities but also anti-obesity and antidiabetic properties in animal models and in humans where flavonols consumption has been associated to a lower risk of type 2 diabetes [ 43 , 236 , 237 , 238 , 239 , 240 , 241 , 242 , 243 ]. Some flavonols inhibited carbohydrate absorption thus lowering postprandial blood glucose mainly through the inhibition of the α-glucosidase activity but also by inhibiting glucose transporters (GLUT2, SGLT1) or other enzymes such as maltase or saccharase [ 236 ].…”