Therapeutic Potential of Ascorbic Acid in the Management of Alzheimer's Disease: An Update.

BACKGROUND: Ascorbic acid is a potent natural antioxidant that protects against oxidative stress and performs various bodily functions. It is commonly found in fruits and vegetables. OBJECTIVE: The manuscript has been written to provide valuable insights into ascorbic acid in managing Alzheimer's disease. METHODS: The data has been gathered from web sources, including PubMed, Science Direct, Publons, Web of Science, and Scopus from 2000-2022 using AA, ascorbic acid, Alzheimer's diseases, memory, dementia, and antioxidant Keywords. RESULTS: In the present manuscript, we have summarized the impact of ascorbic acid and its possible mechanism in Alzheimer's disease by, outlining the information currently available on the behavioral and biochemical effects of ascorbic acid in animal models of Alzheimer's disease as well as its usage as a therapeutic agent to slow down the progression of Alzheimer disease in human beings. Oxidative stress plays a significant role in the advancement of AD. AA is a wellknown antioxidant that primarily reduces oxidative stress and produces protein aggregates, which may help decrease cognitive deficits in Alzheimer's disease. The current paper analyses of ascorbic acid revealed that deficiency of ascorbic acid adversely affects the central nervous system and leads to cognitive defects. However, the results of clinical studies are conflicting, but some of the studies suggested that supplementation of ascorbic acid improved cognitive deficits and decreased disease progression. CONCLUSION: Based on clinical and preclinical studies, it is observed that ascorbic acid supplementation improves cognitive deficits and protects the neurons from oxidative stress injury.

A Narrative Review of Signaling Pathway and Treatment Options for Diabetic Nephropathy.

BACKGROUND: Diabetic nephropathy is a progressive kidney disease that frequently results in end-stage renal disorders and is characterized by proteinuria, albuminuria, decreased filtration, and renal fibrosis. Despite the fact that there are a number of therapeutic alternatives available, DN continues to be the main contributor to end-stage renal disease. Therefore, significant innovation is required to enhance outcomes in DN patients. MATERIAL AND METHODS: Information was collected from online search engines like, Google Scholar, Web of Science, PubMed, Scopus, and Sci-Hub databases using keywords like diabetes, nephropathy, kidney disease, autophagy, etc. Result: Natural compounds have anti-inflammatory and antioxidant properties and impact various signaling pathways. They ameliorate kidney damage by decreasing oxidative stress, inflammatory process, and fibrosis and enhance the antioxidant system, most likely by activating and deactivating several signaling pathways. This review focuses on the role of metabolic memory and various signaling pathways involved in the pathogenesis of DN and therapeutic approaches available for the management of DN. Special attention is given to the various pathways modulated by the phytoconstituents.

Role of Brain Angiotensin-II in Development of Experimental Diabetic Nephropathy in Wistar Rats

Abstract The renin-angiotensin-aldosterone system (RAAS) plays a key role in diabetic nephropathy (DN). Angiotensin-II secreted during the RAAS pathway increases nephropathy. It stimulates oxidative stress which can quench nitric oxide. Reduced nitric oxide level aggravates Ang-II-induced vasoconstriction. Ang-II has also emerged as a central mediator of the glomerular hemodynamic changes that are associated with renal injury. Deletion of ACE2 is also noted due to increased Ang-II level which leads to the development of DN. We hypothesize that nephropathy caused by Ang-II in the periphery may be controlled by brain RAAS. ACE inhibitors and ARBs may show the renoprotective effect when administered through ICV without crossing the blood-brain barrier. DN was observed after 8 weeks of diabetes induction through alloxan. Administration of captopril and valsartan once and in combined therapy for 2 weeks, significantly reduced urine output, blood urea nitrogen, total protein in the urine, serum cholesterol, serum creatinine, serum triglycerides, and kidney/body weight ratio as compared to diabetic control rats. Further, combination therapy significantly increased the body weight and serum nitrate level as compared to diabetic control animals. However, increased ACE2 levels in the brain may reduce the sympathetic outflow and might have decreased the peripheral activity of Ang-II which shows beneficial effects in DN.

Therapeutic approaches of nutraceuticals in the prevention of Alzheimer's disease.

Alzheimer's disease (AD) is a neurological illness that causes memory loss over time. Currently, available pharmaceutical medicines and products are limited, and they have side effects at a higher price. Researchers and scientists have observed significant effects of nutraceuticals. Various preclinical and clinical studies were investigated for the Anti-Alzheimer's activity of nutraceuticals. The increasing ability of the pathogenesis of AD has led to the analysis of novel therapeutic targets, including the pathophysiological mechanisms and distinct cascades. So, current improvement will show the most adequate and prominent nutraceuticals and suggested concise mechanisms involving autophagy regulation, anti-inflammatory, antioxidant, mitochondrial homeostasis, and others. The effects of nutraceuticals cannot be ignored; it is important to investigate high-quality clinical trials. Given the potential of nutraceuticals to battle AD as multi-targeted therapies, it's vital to evaluate them as viable lead compounds for drug discovery and development. To the best of the authors 'knowledge, modification of blood-brain barrier permeability, bioavailability, and aspects of randomized clinical trials should be considered in prospective investigations. PRACTICAL APPLICATIONS: Advancements in molecular diagnostic and fundamentals have implemented particular usefulness for drug evaluation. An excess of experimental knowledge occurs regarding the effect of nutraceuticals on AD. There are various preclinical and clinical studies that have been done on nutraceuticals. In addition, various substitute inhibit and enhance some pathophysiological levels associated with AD. Nutraceuticals are easily available and have fewer side effects with cost-effective advantages. However, further investigations and clinical trials are required to encourage its effect on disease.