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The Potential Effects of Dietary Flavones on Diabetic Nephropathy; a Review of Mechanisms

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The Potential Effects of Dietary Flavones on Diabetic Nephropathy; a Review of Mechanisms J Renal Inj Prev. 2020; 9(2): e09. http://journalrip.com doi: 10.34172/jrip.2020.09 Journal of Renal Injury Prevention The potential effects of dietary flavones on diabetic nephropathy; a review of mechanisms Lida Menati1, Amirhosein Meisami2, Mitra Zarebavani3* ID 1Department of Midwifery, Faculty of Nursing and Midwifery, Kermanshah University of Medical Sciences, Kermanshah, Iran 2Emergency Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran 3Department of Clinical Laboratory Sciences, School of Allied Medical Sciences, Tehran University of Medical Sciences, Tehran, Iran A R T I C L E I N F O A B S T R A C T Article Type: Diabetes as a chronic metabolic disorder affects the worldwide population with high incidence Review of morbidity and mortality. Different complications such as nephropathy, neuropathy, ocular diseases, and cardiovascular disease are common in patients with diabetes that threaten the Article History: patient’s lifestyle. Diabetic nephropathy (DN) usually is related to some major structural Received: 17 November 2019 alterations in the kidney which characterized by generation of toxic reactive oxygen species Accepted: 4 January 2020 (ROS) or inhibition of antioxidant systems in kidney tissue. Different natural agents have Published online: 30 January 2020 been introduced to be used as a complementary treatment to prevent diabetic kidney disease. Flavones (apigenin, luteolin, nobiletin and chrysin) as a subgroup of flavonoids are natural Keywords: occurring substances which have several pharmacological activates, including antioxidant, anti- Diabetic complications apoptotic, anti-inflammatory, and anti-tumor efficacy. Recent evidence indicated that flavones Kidney diseases may be effective for prevention and treatment of diabetes complications in experimental models. Review Flavones The present study was designed to review the relationship between flavones administration Oxidative stress and diabetes and diabetic kidney disease by focusing on the possible molecular pathway. Diabetic nephropathy The findings indicate that flavones have protective effects against diabetic kidney disease by Diabetic kidney disease modulation of different pathways related to oxidative stress, inflammation, and apoptosis in End-stage renal failure animal models. Therefore, more clinical investigations are suggested to be conducted to find the Reactive oxygen species protective effects of flavones in patients with diabetes. Implication for health policy/practice/research/medical education: Reactive oxygen species overproduction in diabetes is known to be associated with the pathways generally lead to inflammation in renal tissue, endothelial dysfunction, and renal fibrosis. Please cite this paper as: Menati L, Meisami A, Zarebavani M. The potential effects of dietary flavones on diabetic nephropathy; a review of mechanisms. J Renal Inj Prev. 2020; 9(2): e09. doi: 10.34172/jrip.2020.09. Introduction diabetic kidney disease has been reported to involve about Diabetes as a chronic metabolic disorder is characterized 15% to 25% of patients with type I diabetes (4) and 30% by hyperglycemia related to lack of insulin (type I) and to 40% of type II diabetes patients (5). Diabetic kidney presence of insulin resistance (type II) (1). Although disease is clinically recognized by a progressive increase the etiology of this disorder is not clear yet, different of albumin level in urine (albuminuria) and a subsequent factors such as autoimmune disease, viral infection, decline in the glomerular filtration rate (GFR) (6). The and environmental causes have been suggested (2). pathogenesis of diabetic kidney disease usually is related Diabetes accompanied by numerous complications in to some major structural alterations in the kidney such patients which commonly affects the cardiovascular as glomerular capillaries enlargement, renal hypertrophy, system, peripheral nerves, kidney, eye, ear, and skin and thickening of glomerular basement membrane due consequently, these are too costly in terms of quality and to excessive deposition of extracellular matrix, and longevity of life (3). mesangial expansion (7). Chronic hyperglycemia affects Diabetic nephropathy (DN) or diabetic kidney disease the function of numerous renal cells. Thereby, podocytes, is one of the most serious complications of diabetes which cells of the tubular and collecting ducts the glomerular causes end-stage renal failure in these patients. Recently, endothelial cells, smooth muscle cells, and mesangial *Corresponding author: Mitra Zarebavani, Ph.D, Email: [email protected] Menati L et al cells may subsequently conduct the activation of several least 6000 phenolic compounds; and some have been pathological processes leading to diabetic kidney disease demonstrated to act as the anti-diabetic agents (19). (8). Several mechanisms have been defined to determine Polyphenols extracted from these natural sources can the underlying effects of hyperglycemia in induction of be used as a supplementary treatment for repairing the tissue damage. Oxidative stress has been demonstrated diabetes-induced damages due to their biological features as a major culprit in kidney disease in diabetes which (20). In addition to the potent antioxidant properties, significantly disrupts renal hemodynamics known to be dietary flavonoids also improve glucose and lipid related to diabetic kidney disease (9). Oxidative stress, metabolism and exhibit anti-inflammatory properties which referred to an imbalance between production of (18). Additionally, natural and plant source agents, such pro-oxidants and antioxidant defenses, plays a crucial as flavonoids with a more specific focus on diabetic renal role in the pathogenesis of diabetes (10). Pro-oxidants are injury, would cause less treatment-related morbidity (21). chemical components are characterized by the generation In the present review, we focused on the connection of toxic reactive oxygen species (ROS) or inhibition of between flavones and diabetic kidney disease on the basis antioxidant systems. Therefore, ROS plays a critical role in of recent studies. The anti-diabetic functions and the high glucose-induced renal dysfunction (5). Accordingly underlying molecular signaling of the flavones found in the compounds are involved in the accumulation of ROS dietary plants, fruits have been investigated using basic are known as antioxidants. Endogenous antioxidants and clinical researches. have an important role in regulation of cellular functions (11). The most efficient enzymatic antioxidants involve Flavones superoxide dismutase (SOD), glutathione peroxidase Flavones (Figure 1) are known as important and powerful (GPx), and catalase (CAT) (12). subgroups. The most famous flavones are luteolin (LUT), Free radicals, the reactive chemical species with apigenin, nobiletin, and chrysin (22). These compounds unstable configuration have a single unpaired electron have a diversity of activities, which contribute to plants in an outer orbit which provides energy to react with adaptation to a terrestrial environment. In addition to adjacent molecules such as lipids, proteins, nucleic acids, the different biochemical, physiological, and ecological and carbohydrates (13). Recent studies provide growing activities in plants, flavones also exhibit biological evidence that the ROS overproduction in diabetes is functions on animals, considering as valuable nutrients known to be associated with the pathways generally lead (23). to inflammation in renal tissue, endothelial dysfunction To discuss the health benefits of flavones, it should be and renal fibrosis (14). noted that, these components have this ability to scavenge There has also been shown that neutralization of ROS. Analysis of structural-activity classification of free radicals can significantly inhibit the development flavonoids identified that LUT is one of the most potent of diabetes complications, although there is still some suppressors of xanthine oxidase which known as a key controversy about administration of antioxidants and its enzyme in ROS production (24). Besides, apigenin effectiveness in lowering the risk of diabetes development prevents endothelial cells from lipopolysaccharide- and its complications (15). Various antioxidants have induced damage during acute inflammation and been suggested for treatment of hyperglycemia-induced modulates mitochondrial activity by reducing ROS (25). damages in diabetes. Vitamins, some components Furthermore, the anti-inflammatory functions of of plants and fresh fruits (16). Additionally, many flavones seem to be related to their ability to modulate diabetic patients prefer to select some alternative and the toll-like receptor/ nuclear factor-kB (NF-kB) which complementary therapies along with mainstream anti- is responsible for the regulation of inflammatory diabetic medications, which can be protective against the mediators e.g. tumor necrosis factor α (TNFα), complications of diabetes (17). interleukin1β (IL1β) and cyclooxygenase-2 (26). Several Flavonoids, as a large family of compounds with common chemical properties are synthesized by plants (18). Flavonoids can be further divided into six major subclasses according to their chemical structure (with C ring generic structure); flavonols (quercetin, rutin kaempferol, morin and myricetin), flavanones (eriodictyol, hesperetin, narigin, taxifolin, fisetin, and naringenin), flavans-3-ol (catechin), isoflavonoids (genistein, genistin, daidzein, and glycitein), flavones (apigenin, luteolin,
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