Dose-Dependent Attenuation of the Efficacy of Clitoria ternatea by Cobalt Oxide Nanoparticles Against Diabetes-Induced Cognitive Impairment.

Diabetes mellitus is a metabolic disorder caused by insulin deficiency, insulin resistance, genetic alterations, and oxidative stress. The high glucose levels may impair the functioning of nerve cells, leading to neurodegenerative diseases, including cognitive impairment. Clitoria ternatea has various pharmacological activities, including antioxidant, anti-inflammatory, antidiabetic, and neuroprotective effects. The present study evaluates the efficacy of fresh flower aqueous extract of Clitoria ternatea against diabetes-induced cognitive impairment. The challenges in delivering drugs targeting the brain possess the limitations of crossing the blood-brain barrier. Metal nanoparticles are considered the most reliable brain drug delivery systems. Considering the neurotoxicity of cobalt oxide, whether it can be used to improve brain delivery is also evaluated. Cobalt oxide nanoparticles (Co3O4 NPs) of fresh flower aqueous extract of Clitoria ternatea are prepared by green synthesis and characterized. The effect of these nanoparticles is compared with Clitoria ternatea extract against Streptozotocin (STZ)-induced cognitive impairment. The behavioral, biochemical, in vivo antioxidant, total thiol content, estimation of proinflammatory cytokines, acetylcholine esterase, and nitrite levels in the brain of STZ-induced diabetic rats revealed that cobalt oxide nanoparticles showed neurotoxicity, whereas C. ternatea showed neuroprotective effect and also improved the cognitive function. The lower dose of cobalt oxide nanoparticles of C. ternatea (2 mg/kg) exhibited a neuroprotective and cognition improvement effect. However, the higher dose (4 mg/kg) of cobalt oxide nanoparticles of C. ternatea showed a neurotoxic effect. Since Co3O4 NPs are neuroprotective at low doses, they can be used for neuroprotective actions. However, dose optimization studies are required.

Efficient removal of environmental pollutants by green synthesized metal nanoparticles of Clitoriaternatea.

Prevention and management of water pollution are becoming a great challenge in the present scenario. Different conventional methods like carbon adsorption, ion exchange, chemical precipitation, evaporation, and biological treatments remove water pollutants. Nowadays, the requirement for effective, non-toxic and safe waste management strategies is very high. Nanomaterials have been explored in various fields due to their unique characteristics. Green synthesis of nanomaterial is becoming more popular due to their safety, non-toxicity, and ease of scale-up technology. Metal nanoparticles can be synthesized using a green synthesis method using biological sources provided by eco-friendly, non-hazardous nanomaterials with superior properties to bulk metals. Hence, this study has designed a green synthesis of magnetic (cobalt oxide) and noble (gold) nanoparticles from the fresh flowers of Clitoria ternatea. The flavonoids and polyphenols in the extract decreased the energy band gap of cobalt oxide and gold nanoparticles; hence, the capping of the natural constituents in Clitoria ternatea helped form stable metal nanoparticles. The cobalt oxide and gold nanoparticles are evaluated for their potential for eliminating organic pollutants from industrial effluent. The novelty of this present work represents the application of cobalt oxide nanoparticles in the removal of organic pollutants and a comparative study of the catalytic behaviour of both metal nanoparticles. The degradation of bromophenol blue, bromocresol green, and 4-nitrophenol in the presence of gold nanoparticles was completed in 120, 45, and 20 min with rate constants of 3.7 × 10-3/min, 6.9 × 10-3/min, and 16.5 × 10-3/min, respectively. Similarly, the photocatalysis of bromophenol blue, bromocresol green, and 4-nitrophenol in the presence of cobalt oxide nanoparticles was achieved in 60, 90, and 40 min with rate constants of 2.3 × 10-3/min, 1.8 × 10-3/min, and 1.7 × 10-3/min, respectively. The coefficient of correlation (R2) values justify that the degradation of organic pollutants follows first-order kinetics. The significance of the study is to develop green nanomaterials that can be used efficiently to remove organic pollutants in wastewater using a cost-effective method with minimal toxicity to aquatic animals. It has proved to be useful in environmental pollution management.

Phytomolecules from conventional to nano form: Next-generation approach for Parkinson's disease.

The incidence of neurodegenerative diseases is increasing exponentially worldwide. Parkinson's disease (PD) is a neurodegenerative disease caused by factors like oxidative stress, gene mutation, mitochondrial dysfunction, neurotoxins, activation of microglial inflammatory mediators, deposition of Lewy's bodies, and α- synuclein proteins in the neurons leading to neuroinflammation and neurodegeneration in the substantia nigra. Hence the development of efficacious neuro-therapy is in demand which can prevent neurodegeneration and protect the nigrostriatal pathway. One of the approaches for managing PD is reducing oxidative stress due to aging and other co-morbid diseased conditions. The phytomolecules are reported as safe and efficacious antioxidants as they contain different secondary metabolites. However, the limitations of low solubility restricted permeability through the blood-brain barrier, and low bioavailability limits their clinical evaluation and application. This review discusses the therapeutic efficacy of phytomolecules in PD and different nanotechnological approaches to improve their brain permeability.

Metal Nanoparticles in Alzheimer's Disease.

Nanotechnology has emerged in different fields of biomedical application, including lifestyle diseases like diabetes, hypertension, and chronic kidney disease, neurodegenerative diseases like Alzheimer's disease (AD), Parkinson's disease, and different types of cancers. Metal nanoparticles are one of the most used drug delivery systems due to the benefits of their enhanced physicochemical properties as compared to bulk metals. Neurodegenerative diseases are the second most cause affecting mortality worldwide after cancer. Hence, they require the most specific and targeted drug delivery systems for maximum therapeutic benefits. Metal nanoparticles are the preferred drug delivery system, possessing greater blood-brain barrier permeability, biocompatibility, and enhanced bioavailability. But some metal nanoparticles exhibit neurotoxic activity owing to their shape, size, surface charge, or surface modification. This review article has discussed the pathophysiology of AD. The neuroprotective mechanism of gold, silver, selenium, ruthenium, cerium oxide, zinc oxide, and iron oxide nanoparticles are discussed. Again, the neurotoxic mechanisms of gold, iron oxide, titanium dioxide, and cobalt oxide are also included. The neuroprotective and neurotoxic effects of nanoparticles targeted for treating AD are discussed elaborately. The review also focusses on the biocompatibility of metal nanoparticles for targeting the brain in treating AD. The clinical trials and the requirement to develop new drug delivery systems are critically analyzed. This review can show a path for the researchers involved in the brain-targeted drug delivery for AD.

Ameliorative and Neuroprotective Effect of Core-Shell Type Se@Au Conjugated Hesperidin Nanoparticles in Diabetes-Induced Cognitive Impairment.

Diabetes mellitus is the most chronic metabolic ailment characterized by insulin deficiency leading to aberrant cognitive dysfunction in later stages. Hesperidin is a bioflavonoid, having different pharmacological activities, but its poor water solubility and short plasma half-life restrict its applications in the clinical field. So, the hesperidin was conjugated with gold, selenium, and core-shell bimetallic nanoparticles of gold and selenium. Different spectroscopic methods characterized the synthesized monometallic and bimetallic nanoparticles. The rats were injected with streptozotocin to induce cognitive dysfunction, followed by administering HSP, HSP-Au NPs, HSP-Se NPs, and Se@Au-HSP NPs daily for 21 days. Then, the neurobehavioral studies, oxidative stress parameters, AChE and nitrite levels, the content of amyloid-ß42, and inflammatory mediators were accessed to evaluate the effect of the nanoparticles against the STZ rat model. The results showed a significant increase in oxidative stress, AChE activity, amyloid-ß42, nitrite levels, and neuroinflammation by upregulating the inflammatory cytokines in the streptozotocin-administered rat brain. The HSP, HSP-Au NPs, HSP-Se NPs, and Se@Au-HSP NPs effectively reversed all these effects of streptozotocin. However, the bimetallic nanoparticle Se@Au-HSP NPs revealed better neuroprotective action than HSP-Au NPs and HSP-Se NPs. Hesperidin-conjugated bimetallic nanoparticles improved learning and memory in the STZ rat model and may be an alternative approach for neurodegenerative diseases, including Alzheimer's disease.

New insights toward molecular and nanotechnological approaches to antidiabetic agents for Alzheimer's disease.

Alzheimer's disease (AD) is a chronic neurodegenerative disorder affecting a major class of silver citizens. The disorder shares a mutual relationship on account of its cellular and molecular pathophysiology with type-II diabetes mellitus (DM). Chronic DM increases the risk for AD. Emerging evidence recommended that resistance in insulin production develops cognitive dysfunction, which generally leads to AD. Repurposing of antidiabetic drugs can be effective in preventing and treatment of the neurodegenerative disorder. Limitations of antidiabetic drugs restrict the repurposing of the drugs for other disorders. Therefore, nanotechnological intervention plays a significant role in the treatment of neurological disorders. In this review, we discuss the common cellular and molecular pathophysiologies between AD and type-II DM, the relevance of in vivo models of type II DM in the study of AD, and the repurposing of antidiabetic drugs and the nanodelivery systems of antidiabetic drugs against AD.

Photocatalysis of environmental organic pollutants and antioxidant activity of flavonoid conjugated gold nanoparticles.

The unique properties of nanomaterials have the potential application in different fields of biomedical application along with the management of environmental pollutants. This research work involved the isolation of hesperidin from the orange peel and the preparation of hesperidin gold nanoparticles by the chemical reduction method. The high substrate specificity and lower band gap enable the excitation of gold nanoparticles in visible light. Hence gold nanoparticles are chosen nowadays for the management and removal of organic pollutants. The efficacy of hesperidin gold nanoparticles was evaluated by the photocatalytic activity on organic dyes and pollutants like methyl orange, methylene blue, bromocresol green, and 4 - nitro phenol with sodium borohydride as reducing agent and the antioxidant study by scavenging of free radicals of DPPH, ABTS, and hydroxyl free radicals of hydrogen peroxide. The kinetics of photocatalytic degradation of organic dyes and 4 - nitro phenol was found to follow the first order with rate constants of 10 × 10-3, 37 × 10-3, 23 × 10-3 and 49 × 10-3 min-1 for methyl orange, methylene blue, bromocresol green and 4 - nitro phenol respectively. The hesperidin gold nanoparticles showed significant antioxidant activity as compared to ascorbic acid as standard. The flavonoid conjugated gold nanoparticles can be an efficient antioxidant and photocatalyst for the management of different diseases and wastewater treatment respectively.

Type II diabetes mellitus: a review on recent drug based therapeutics.

Diabetes mellitus (DM) is a metabolic disorder that occurs in the body because of decreased insulin activity and/or insulin secretion. Pathological changes such as nephropathy, retinopathy, and cardiovascular complications inevitably occur in the body with the progression of the disease. DM is mainly categorized into 2 sub-types, type I DM and type II DM. While type I DM is generally treated through insulin replacement therapy, type II DM is treated with oral hypoglycaemics. The major drug therapy for type II DM comprises of insulin secretagogues, biguanides, insulin sensitizers, alpha glucosidase inhibitors, incretin mimetics, amylin antagonists and sodium-glucose co-transporter-2 (SGLT2) inhibitors. Dual drug therapies are often recommended in patients who are unable to achieve therapeutic goals with first line oral hypoglycaemic agents as monotherapy. Inspite of the appreciable therapeutic benefits, the conventional dosage forms depicts differential bioavailability and short half-life, mandating frequent dosage and causing greater side effects leading to therapy ineffectiveness and patient non-compliance. Given the pathological complexity of the said disease, nanotechnology-based approaches are more enticing as it comes with added advantage of site-specific drug delivery with higher bioavailability and reduced dosage regimen. In the present review article, we have made an attempt to explore the pathophysiology of type II DM, the conventional treatment approaches (mono and combination therapy) as well as the nano based drug delivery approaches for the treatment of type II DM.

Preparation and mechanistic aspect of natural xanthone functionalized gold nanoparticle.

Herein, a facile scale up and shape variable synthesis of gold nanoparticle (AuNP) and reaction mechanism by natural xanthone derivative (mangiferin) has been reported. Mangiferin (C19H18O11; 1,3,6,7-tetrahydroxyxanthone-C2-ß-d-glucoside), a xanthone derivative is isolated from Mangifera indica L. leaves which efficiently reduces Au3+ ions to Au0 and stabilizes the formed AuNP. The structural, optical and plasmonic properties of synthesized AuNP have been investigated through different instrumental techniques like UV-Vis and FTIR spectroscopy, powder XRD, FESEM and TEM analysis. It is observed that variation of the concentration of Au3+ ions and mangiferin has a great effect on controlling size and shape of nanoparticles. The role of reaction temperature is also notable. An interesting observation is that with same concentration ratio of HAuCl4/mangiferin (0.025 mM/0.002%) at the room temperature kidney shaped AuNP is produced, whereas it is spherical at boiling temperature. Moreover, mangiferin allows high scale synthesis of AuNPs (0.025 mM to 10 mM) without changing the particles size and shape. The mechanistic investigation through UV-Vis, FTIR and GCMS analyses reveal the cleavage of glucose unit and oxidation of phenolic OH groups during AuNP formation. Non-toxicity of mangiferin conjugated AuNP on normal human breast cell line (MCF-10A) suggesting its future application as a drug delivery system and other related medicinal purposes.