The protective effects of flavonoids and carotenoids against diabetic complications—A review of in vivo evidence

Abstract

Diabetes mellitus is a chronic metabolic disorder caused either by inadequate insulin secretion, impaired insulin function, or both. Uncontrolled diabetes is characterized by hyperglycemia which over time leads to fatal damage to both macro-and microvascular systems, causing complications such as cardiovascular diseases, retinopathy and nephropathy. Diabetes management is conventionally delivered through modifications of diet and lifestyle and pharmacological treatment, using antidiabetic drugs, and ultimately insulin injections. However, the side effects and financial cost of medications often reduce patient compliance to treatment, negatively affecting their health outcomes. Natural phytochemicals from edible plants such as fruits and vegetables (F&V) and medicinal herbs have drawn a growing interest as potential therapeutic agents for treating diabetes and preventing the onset and progression of diabetic complications. Flavonoids, the most abundant polyphenols in the human diet, have shown antidiabetic effects in numerous in vitro and preclinical studies. The underlying mechanisms have been linked to their antioxidant, anti-inflammatory and immunomodulatory activities. Carotenoids, another major group of dietary phytochemicals, have also shown antidiabetic potential in recent in vitro and in vivo experimental models, possibly through a mechanism of action similar to that of flavonoids. However, scientific evidence on the efficacy of these phytochemicals in treating diabetes or preventing the onset and progression of its complications in clinical settings is scarce, which delays the translation of animal study evidence to human applications and also limits the knowledge on their modes of actions in diabetes management. This review is aimed to highlight the potential roles of flavonoids and carotenoids in preventing or ameliorating diabetes-related complications based on in vivo study evidence, i.e., an array of preclinical animal studies and human intervention trials. The current general consensus of the underlying mechanisms of action exerted by both groups of phytochemicals is that their anti-inflammatory action is key. However, other potential mechanisms of action are considered. In total, 50 in vivo studies were selected for a review after a comprehensive database search via PubMed and ScienceDirect from January 2002 to August 2022. The key words used for analysis are type-2 diabetes (T2DM), diabetic complications, flavonoids, carotenoids, antioxidant, anti-inflammatory, mechanisms of prevention and amelioration, animal studies and human interventions.

Translational Research on Bee Pollen as a Source of Nutrients: A Scoping Review from Bench to Real World

“…A countless number of studies unveiling the antidiabetic properties, including early preventive, disease course modifying, and complication limiting effects, of individual nutrients and phytochemicals that are ubiquitously present in BP from different botanical and geographical origins have been published so far. This includes, for example, nutrients including vitamins such as groups B [ 241 , 242 , 243 ], C [ 244 , 245 , 246 ], D [ 247 , 248 , 249 ], and E [ 128 , 250 , 251 ], oligo-elements and other minerals [ 252 , 253 , 254 ], and lipids such as unsaturated fatty acids [ 255 , 256 , 257 ] and phytosterols [ 63 , 258 , 259 ], as well as other phytochemicals including polyphenols such as phenolic acids, flavonoids, and stilbenes (very recent and comprehensive reviews of preclinical and clinical evidence can be found in [ 260 , 261 , 262 , 263 , 264 , 265 , 266 ]). Despite the substantial amount of experimental and clinical evidence of all these BP compounds in the complex pathophysiology of diabetes and in its interaction with other comorbidities, the possible synergistic potential and real clinical outcome of these compounds, which are always combined in BP, have generally been omitted in research and must be further studied by in vivo experiments, and subsequently verified and objectively assessed by clinical studies.…”

β-Asarone Alleviates High-Glucose-Induced Oxidative Damage via Inhibition of ROS Generation and Inactivation of the NF-κB/NLRP3 Inflammasome Pathway in Human Retinal Pigment Epithelial Cells

“…Excess ROS production due to hyperglycemia initiates oxidative stress and inflammatory responses, which are mechanisms involved in the pathogenesis of DR [3,7]. Antioxidants with antiinflammatory effects exert inhibitory effects on the onset and progression of DR [41][42][43]. β-asarone, a type of volatile oil, exerts multiple pharmacological effects, including antioxidant and anti-inflammatory effects [19,20,44].…”

Algae-Derived Natural Products in Diabetes and Its Complications—Current Advances and Future Prospects

“…Future research should aim to conduct comprehensive preclinical investigations to validate the therapeutic potential of algae-derived compounds in the relevant animal models of diabetes and its complications. Subsequently, well-controlled clinical trials involving diverse patient populations will provide valuable insights into the efficacy, optimal dosage, and long-term effects of algae-based interventions [ 32 , 36 ].…”

“…Diabetic retinopathy, a microvascular complication, is characterized by oxidative stress and inflammation in the retina. Algae-derived compounds, with their antioxidant and anti-inflammatory properties, have shown potential for protecting retinal cells and preventing the progression of retinopathy [ 35 , 36 ]. Similarly, algae-derived compounds have demonstrated reno-protective effects by reducing albuminuria, attenuating renal fibrosis, and modulating the inflammatory pathways, providing a potential avenue for managing diabetic nephropathy [ 37 , 38 ].…”