Current Concepts in the Molecular Mechanisms and Management of Diabetic Neuropathy by Pharmacotherapeutics and Natural Compounds.

One of the most crippling effects of diabetes mellitus is diabetic neuropathy, which can cause discomfort, loss of movement, and even amputation. Diabetic neuropathy manifests in a variety of ways, ranging from pain to death. Diagnosing diabetic neuropathy can be challenging since it often goes unnoticed for many years following the onset of diabetes. In addition to oxidative stress in neurons, hyperglycemia activates a number of metabolic pathways that are important sources of damage and possible targets for treatment in diabetic neuropathy. Downstream metabolic cascades caused by prolonged hyperglycemia include activation of protein kinase C, increased production of advanced glycation end products, excessive release of cytokines, increased oxidative stress, and injury to peripheral nerves. Despite the fact that these metabolic anomalies are considered the main cause of diabetes-related microvascular issues, the diverse mechanistic processes of neuropathy are characterized by organ-specific histological and biochemical features. Although the symptoms of diabetic neuropathy can be treated, there are few options to correct the underlying problem. Diabetic neuropathy exerts a tremendous financial, psychological, and physical burden on society, emphasizing the need for efficient and focused treatment. The major goal of this review is to shed light on the multiple mechanisms and pathways that contribute to the onset of diabetic neuropathy and to provide readers with a comprehensive understanding of emerging therapeutic strategies to postpone or reverse various forms of diabetic neuropathy. The article discusses available medications and provides the latest guidelines for the treatment of pain and distal symmetric polyneuropathy, including diabetic autonomic neuropathy, which may help the patients control pain well and assess alternatives for treatment that might be more successful in preventing or delaying the course of a disease.

Neuroprotective Effects of Isolated Mangiferin from Swertia chirayita Leaves Regulating Oxidative Pathway on Streptozotocin-Induced Diabetic Neuropathy in Experimental Rats.

BACKGROUND: Oxidative stress has an important role in the pathogenesis and development of diabetic peripheral neuropathy (DPN), the most common and debilitating complication of diabetes mellitus. Swertia chirayita is a rich source of phenolic constituents and has hypoglycemic, anti-inflammatory, and antioxidant properties. AIMS: This study was performed to evaluate the neuroprotective effect in diabetes by enhancing antioxidant defense against oxidative stress, which exhibits a neuroprotective effect in streptozotocin- induced diabetic rats. OBJECTIVES: The objective of this study was to elucidate the therapeutic potential of bioactive compounds of Swertia chirayita for diabetic complications. METHODS: The present work focused on isolating the bioactive from the leaves of Swertia absinthe for acute toxicity studies, assessing its protective effects against diabetes and diabetic neuropathy as well as its mode of action in STZ-induced Wistar rats. The local area of Moradabad is the place from where the leaves of Swertia chirayita were gathered. Mangiferin was isolated and identified using spectroscopic techniques, such as UV, HPLC, 1H NMR, C13 NMR, MAS, and FTIR. Mangiferin was administered in doses of 15 and 30 mg/kg to test its effect on experimentally induced diabetes. The sciatic nerves of all groups were examined histopathologically. The protective effect of the drug against diabetes and diabetic neuropathy was demonstrated by measures, such as blood glucose level, body weight, food intake, thermal hyperalgesia, grip strength, spontaneous locomotor test, and lipid profile analysis. Sciatic nerve cells of the treated groups showed less inflammation, degeneration, and necrosis. RESULTS: The results of this study confirmed that mangiferin alleviated diabetic neuropathic pain, possibly by reducing inflammatory cytokines (TNF-α, TGF-ß1, IL-1ß, and IL-6), strong antioxidant activity, and NGF in sciatic nerves. It may be a therapeutic agent. CONCLUSION: Our results suggested that active phytochemicals of Swertia chirayita showed preventive and curative effects against STZ-induced diabetic neuropathy in rats, which might be due to its antioxidant, anti-inflammatory, and anti-apoptotic properties.

Review on In-vitro Techniques and In-vivo Animals Models for Screening Diabetes and Diabetic Complications.

Diabetes mellitus is a type of metabolic disorders. Various pharmaceutical interventions and animal models have been used to investigate the genetic, environmental, and etiological aspects of diabetes and its effects. In recent years for the development of ant-diabetic remedies, numerous novel genetically modified animals, pharmaceutical substances, medical techniques, viruses, and hormones have been developed to screen diabetic complications. A unique disease-treating drug with new properties is still being sought after. The current review tried to include all published models and cutting-edge techniques. Experimental induction of diabetes mellitus in animal models and in vitro methods are essential for advancing our knowledge, a thorough grasp of pathophysiology, and the creation of novel therapeutics. Animal models and in vitro techniques are necessary to develop innovative diabetic medications. New approaches and additional animal models are required for diabetes research to advance. This is particularly true for models produced via dietary modifications, which have various macronutrient compositions. In this article, we review the rodent models of diet-induced diabetic peripheral neuropathy, diabetic retinopathy, and diabetic nephropathy and critically compare the key characteristics of these micro-vascular complications in humans and the diagnostic criteria with the parameters used in preclinical research using rodent models, taking into consideration the potential need for factors that can accelerate or aggravate these conditions.

Toxicological Assessment and Anti-diabetic Effects of Combined Extract of Chirata, Fenugreek and Sesame on Regulating TNF-α, TGF-ß and Oxidative Stress in Streptozotocin Induced Diabetic Rats.

BACKGROUND: Swertia chirayita, Trigonella foenum-gracum and Sesamum indicum are used as traditional medicines to treat diabetes mellitus. A collection of metabolic illnesses known as diabetes mellitus (DM) involves chronic hyperglycemia caused by flaws in insulin secretion, function, or both. Innate immunity and inflammation both play important roles in the etiology of diabetes-related microvascular problems. OBJECTIVE: This study aims to examine the anti-diabetic effects and the acute toxicity of combined extract (1:1:1) of Swertia chirayita, Trigonella foenum-gracum and Sesamum indicum. To address the demand for higher effectiveness and safety, the current effort aims to construct anti-diabetic preparations containing methanolic extract from herbal medications. METHODS: The OECD 423 method was used to investigate acute toxicity in rats. Rats were used as test subjects, and rats were given a 35 mg/kg BW injection of streptozotocin to develop diabetes. The diabetic control group was given Glibenclamide 25 mg/kg BW, while the experimental group's diabetic rats received 125 mg/kg BW and 250 mg/kg BW of a combined methanolic extract of all plants. Among the measurements looked at were acute oral toxicity, behavioral changes, body weight, serum glucose levels, lipid profiles, oxidative stress, renal function tests, and inflammatory mediators. All the rat groups' histopathologies of the kidney, liver, and stomach were compared. The data were evaluated using analysis of variance, and a post hoc test was then carried out. RESULTS: The combined extracts' medium lethal doses (LD50) were higher than 2000 mg/kg, indicating that they are not poisonous under the conditions that can be observed. Streptozotocin-induced diabetic rats' elevated blood glucose was found to be considerably lower (p 0.01) in the treated group of rats. In the treated group of rats, it was discovered that the damage and disarray in the cells typical of Streptozotocin-induced DM had been repaired. The treated group of rats returned to normal levels of the lipid profile, hyperglycemia, decreased serum protein and liver glycogen, increased liver function, and kidney function markers seen in the rats of the DM control group. CONCLUSION: The evaluated combined methanolic extract can be considered safe for use in rats. Combining methanolic extract from all selected medicinal plants (Swertia chirayita, Trigonella foenum-gracum and Sesamum indicum) has a potential anti-diabetic effect and can be safely developed as an alternative medicine.