A brief study of Nox 4 inhibitors in diabetic nephropathy

The purpose of the study was to find the merits and demerits of NADPH oxidase 4 (Nox 4) inhibitors. Nox inhibitors are tested from natural sources like green tea, plumbagin, Chinese formulas like Baoshenfang, Cudrania tricuspidata, Huangqi decoction and synthetic dual Nox inhibitors. Some of them activate and regulate AMP-activated protein kinase (AMPK). Some chunk the high glucose activated alleyway, dawdling the succession of diabetic nephropathy (DN). Overall, the benefits of NOX are: reducing oxidative damage, improving renal function, reducing podocyte injury, preventing interstitial fibrosis, regulating AMPK which inhibits reactive oxygen species (ROS) and transforming growth factor-beta (TGF-beta), decreasing inflammation due to high glucose, protecting mesangial cells, decreasing collagen synthesis, and reducing glomerular hypertrophy. While targeting NOX in renal impairment, off-target effects, especially cardiovascular effects, are one of the major hurdles since diabetes mellitus (DM) is associated with co-morbid cardiovascular problems

Plant Flavonoids on Oxidative Stress-Mediated Kidney Inflammation

© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).Simple Summary: Increased stress is often observed in patients with kidney diseases, contributing to renal injury progression. Flavonoids are naturally occurring plant compounds with known health benefits, including antiapoptotic, anti-inflammatory, and antioxidant properties. Flavonoids can protect the kidney by improving antioxidant status, ameliorating excess reactive oxygen species levels, and acting as Nrf2-mediators in generating antioxidant responses in the body. Flavonoids also modulate inflammatory markers, exert anti-inflammatory effects, and protect the cells from apoptotic cell death in the kidney. Interestingly, few clinical trials have reported a direct correlation between a flavonoid-rich diet and better kidney disease prognosis. However, flavonoids have a low bioavailability in the body, making it essential to understand better their molecular mechanism of action. We suggest that a flavonoid-rich diet could have promising nephroprotective effects and beneficial outcomes in treating patients with kidney diseases. Abstract: The kidney is susceptible to reactive oxygen species-mediated cellular injury resulting in glomerulosclerosis, tubulointerstitial fibrosis, tubular cell apoptosis, and senescence, leading to renal failure, and is a significant cause of death worldwide. Oxidative stress-mediated inflammation is a key player in the pathophysiology of various renal injuries and diseases. Recently, flavonoids’ role in alleviating kidney diseases has been reported with an inverse correlation between dietary flavonoids and kidney injuries. Flavonoids are plant polyphenols possessing several health benefits and are distributed in plants from roots to leaves, flowers, and fruits. Dietary flavonoids have potent antioxidant and free-radical scavenging properties and play essential roles in disease prevention. Flavonoids exert a nephroprotective effect by improving antioxidant status, ameliorating excessive reactive oxygen species (ROS) levels, and reducing oxidative stress, by acting as Nrf2 antioxidant response mediators. Moreover, flavonoids play essential roles in reducing chemical toxicity. Several studies have demonstrated the effects of flavonoids in reducing oxidative stress, preventing DNA damage, reducing inflammatory cytokines, and inhibiting apoptosis-mediated cell death, thereby preventing or improving kidney injuries/diseases. This review covers the recent nephroprotective effects of flavonoids against oxidative stress-mediated inflammation in the kidney and their clinical advancements in renal therapy.Peer reviewe

The pharmacological potential of hesperidin

287-300The modern scientific society has presently recognized flavonoids to be a unique class of therapeutic molecules due to their varied therapeutic properties. Of these, hesperidin, found along with vitamin C, has been explored for a number of pharmacological effects. Citrus and oranges possess hesperidin as one of the active constituents. Today, hesperidin has been well recognized for its beneficial effects on health. The present review highlights the current information and health-promoting effects of hesperidin. The review uncovers protective effects of hesperidin on functions and integrity of liver, kidney, heart, and age related memory impairment. Hesperidin demonstrated the antimicrobial, anticancer, antihypertensive and antiulcer effect. The present review focus on current information of hesperidin and its active metabolite hesperetin. Along with this, the chemotherapeutic potential of the same has also discussed

The pharmacological potential of hesperidin

The modern scientific society has presently recognized flavonoids to be a unique class of therapeutic molecules due to their varied therapeutic properties. Of these, hesperidin, found along with vitamin C, has been explored for a number of pharmacological effects. Citrus and oranges possess hesperidin as one of the active constituents. Today, hesperidin has been well recognized for its beneficial effects on health. The present review highlights the current information and health-promoting effects of hesperidin. The review uncovers protective effects of hesperidin on functions and integrity of liver, kidney, heart, and age related memory impairment. Hesperidin demonstrated the antimicrobial, anticancer, antihypertensive and antiulcer effect. The present review focus on current information of hesperidin and its active metabolite hesperetin. Along with this, the chemotherapeutic potential of the same has also discussed

The coming age of flavonoids in the treatment of diabetic complications

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 eficacy 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 drugsThis paper was not funded. The authors work has been supported by FEDER-ISCIII Funds (PI17/00130, PI17/01495), Spanish Ministry of Economy and Competitiveness (RTI2018-098788-B-100, DTS17/00203, DTS19/00093, RYC-2017-22369), Spanish Society of Cardiology (SEC), Spanish Society of Nephrology (SEN) and Spanish Society of Atherosclerosis (SEA). TCO is an employee of FAES Pharma. The authors (except JAM) have an ongoing research project in common with FAES Pharma on Flavonoids in diabetic complications under the auspices of the joint-RETOS Collaborations Project 2017 (RTC-2017-6089-1), program supported by Spanish Ministry of Economy and Competitiveness

A recent review of citrus flavanone naringenin on metabolic diseases and its potential sources for high yield-production

Background: Metabolic syndromes are the multi-metabolic abnormality characterized by hyperlipidemia, obesity, hyperglycemia, diabetes, hypertension, cardiovascular disease, and neuro-dysfunction. Naringenin, a naturally occurring flavanone compound, abundantly found in citrus fruit, has demonstrated diverse biological activities. In this context, the role of naringenin in the treatment of metabolic disease and alternative sources for high-yield production of naringenin have recently drawn full scientific attention and become an important issue in research. Scope and approach: This review focuses on recent findings of naringenin against metabolic disorders including oxidative stress, hyperlipidemia, obesity, diabetes, inflammation, and organ toxicity. Also, this review highlights the potential sources of naringenin production. Key findings and conclusions: Naringenin exerts its protective effect against metabolic diseases through multiple mechanisms including its antioxidant activity by scavenging free radicals, inducing antioxidant enzymes and targeting on phosphoinositide 3-kinase/protein Kinase B/nuclear factor (erythroid-derived 2)-like 2 (PI3K/Akt/Nrf2), nuclear factor (erythroid-derived 2)-like 2/antioxidant responsive element (NRf2/ARE), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB), mitogen-activated protein kinase (MAPK), 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase, peroxisome proliferator-activated receptor (PPAR), and nitric oxide-cGMP-protein kinase G-induced KATP channel (NO-cGMP-PKG-KATP). Moreover, microbial production is recommended as a promising alternative method for large-scale production of naringenin. In conclusion, naringenin is a promising compound for the prevention and management of metabolic diseases. Further clinical studies and trials are needed to prove its protective effects on metabolic syndrome in the human population

Flavonoids improve type 2 diabetes mellitus and its complications: a review

The prevalence of type 2 diabetes mellitus (T2DM) is increasing every year. Medications are currently the most common therapy for T2DM. However, these medications have certain adverse effects. In order to find safe and effective ways to improve this disease, researchers have discovered that some natural products can decrease blood sugar. Flavonoids are one of the most essential low molecular weight phenolic chemicals in the plant world, which widely exist in plant roots, stems, leaves, flowers, and fruits. They possess a variety of biological activities, including organ protection, hypoglycemic, lipid-lowering, anti-oxidative and anti-inflammatory effects. Some natural flavonoids ameliorate T2DM and its complications through anti-oxidation, anti-inflammatory action, glucose and lipid metabolism regulation, insulin resistance management, etc. Hence, this review aims at demonstrating the potential benefits of flavonoids in T2DM and its complications. This laid the foundation for the development of novel hypoglycemic medications from flavonoids

Naringin attenuates diabetic retinopathy by inhibiting inflammation, oxidative stress and NF-κB activation in vivo and in vitro

Objective(s): Naringin, an essential flavonoid, inhibits inflammatory response and oxidative stress in diabetes. However, whether naringin has beneficial effects on diabetic retinopathy (DR) remains unknown. Materials and Methods: Streptozotocin (STZ, 65 mg/kg) was intraperitoneally injected into male rats (8 weeks old weighting 200-250 g) to establish diabetic model, then naringin (20, 40 or 80 mg/kg/day) was intraperitoneally injected into the diabetic rats for twelve weeks. Glial fibrillary acidic protein (GFAP) level, thickness of ganglion cell layer (GCL) and ganglion cell counts were assessed in diabetic retina in vivo. Naringin (50 μM) that significantly inhibited high glucose (HG, 25 mM)-induced cell proliferation was used to treat rat Muller cell line (rMC1) in vitro. Inflammatory response, oxidative stress and activation of nuclear factor kappa B (NF-κB) p65 were evaluated in retina in vivo and in rMC1 cells in vitro. Results: Naringin alleviated DR symptoms as evidenced by the increased retinal ganglion cells and decreased GFAP level in rat retina. Naringin exhibited anti-inflammatory and antioxidative effects as confirmed by the down-regulated pro-inflammatory cytokines, tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6), and the up-regulated antioxidants, glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) in DR rats. Moreover, we found that naringin inhibited HG-induced proliferation, abnormal inflammatory response and oxidative stress in rMC1 cells. In addition, the enhanced nuclear translocation of NF-κB p65 in diabetic rat retina and HG-induced rMC1 cells was suppressed by naringin. Conclusion: Naringin attenuates inflammatory response, oxidative stress and NF-κB activation in experimental models of DR

Impact of phytochemicals on PPAR receptors : implications for disease treatments

Peroxisome proliferator-activated receptors (PPARs) are members of the ligand-dependent nuclear receptor family. PPARs have attracted wide attention as pharmacologic mediators to manage multiple diseases and their underlying signaling targets. They mediate a broad range of specific biological activities and multiple organ toxicity, including cellular differentiation, metabolic syndrome, cancer, atherosclerosis, neurodegeneration, cardiovascular diseases, and inflammation related to their up/downstream signaling pathways. Consequently, several types of selective PPAR ligands, such as fibrates and thiazolidinediones (TZDs), have been approved as their pharmacological agonists. Despite these advances, the use of PPAR agonists is known to cause adverse effects in various systems. Conversely, some naturally occurring PPAR agonists, including polyunsaturated fatty acids and natural endogenous PPAR agonists curcumin and resveratrol, have been introduced as safe agonists as a result of their clinical evidence or preclinical experiments. This review focuses on research on plant-derived active ingredients (natural phytochemicals) as potential safe and promising PPAR agonists. Moreover, it provides a comprehensive review and critique of the role of phytochemicals in PPARs-related diseases and provides an understanding of phytochemical-mediated PPAR-dependent and -independent cascades. The findings of this research will help to define the functions of phytochemicals as potent PPAR pharmacological agonists in underlying disease mechanisms and their related complications

Effects of Polyphenols on Oxidative Stress-Mediated Injury in Cardiomyocytes

Cardiovascular diseases are the main cause of mortality and morbidity in the world. Hypertension, ischemia/reperfusion, diabetes and anti-cancer drugs contribute to heart failure through oxidative and nitrosative stresses which cause cardiomyocytes nuclear and mitochondrial DNA damage, denaturation of intracellular proteins, lipid peroxidation and inflammation. Oxidative or nitrosative stress-mediated injury lead to cardiomyocytes apoptosis or necrosis. The reactive oxygen (ROS) and nitrogen species (RNS) concentration is dependent on their production and on the expression and activity of anti-oxidant enzymes. Polyphenols are a large group of natural compounds ubiquitously expressed in plants, and epidemiological studies have shown associations between a diet rich in polyphenols and the prevention of various ROS-mediated human diseases. Polyphenols reduce cardiomyocytes damage, necrosis, apoptosis, infarct size and improve cardiac function by decreasing oxidative stress-induced production of ROS or RNS. These effects are achieved by the ability of polyphenols to modulate the expression and activity of anti-oxidant enzymes and several signaling pathways involved in cells survival. This report reviews current knowledge on the potential anti-oxidative effects of polyphenols to control the cardiotoxicity induced by ROS and RNS stress