Alleviation of Diabetic Retinopathy by Glucose-Triggered Delivery of Vitamin D via Dextran-Gated Functionalized Mesoporous Silica Nanoparticles.

Diabetic retinopathy (DR) is the most common retinal disorder, developed in 35% of patients with diabetes mellitus. Lower serum levels of 25-hydroxyvitamin D are associated with the increased risk of developing DR. High doses of the active form of vitamin D (VD), on the contrary, for a long period of time may lead to hypercalcemia and an imbalance in the regulation of bone metabolism. Herein, we studied the efficacy of dextran-gated carboxyphenylboronic acid (CPBA)-functionalized mesoporous silica nanoparticles (MSNs) for glucose-sensitive delivery of 1,25-dihydroxyvitamin D3 to modulate cellular oxidative stress and inflammation for managing DR. The physical adsorption technique was employed to load VD onto nanoparticles (263.63 µg/mg (w/w)). In the presence of glucose, the dextran molecules detach from pores, allowing VD to release since glucose has 1,2-cis diol groups which have very high affinity to CPBA. Approximately 75% of VD was released upon exposure to 25 mM glucose at a time point of 10 h, demonstrating glucose-responsive delivery. Furthermore, MSN-CPBA was able to deliver VD in a glucose-dependent manner and improve the bioavailability of VD. In high-glucose-supplemented human retinal cells, MSN-CPBA increased the bioavailability of VD and reduced cellular oxidative stress and inflammation. The results suggested that the VD-loaded nanocarrier exerted remarkable therapeutic capacity in reducing the risk of developing DR. By using MSN-CPBA as a delivery platform with dextran gating, the research proposes an effective treatment approach for improving the bioavailability and effectiveness of a hydrophobic molecule in the treatment of DR.

Mesoporous Silica Nanoparticles: Drug Delivery Vehicles for Antidiabetic Molecules.

Mesoporous silica nanoparticles (MSNs) are promising nanomaterials that are widely used in biomedical applications like drug delivery, diagnosis, bio-sensing and cell tracking. MSNs have been investigated meticulously in the drug-delivery field due to their unique chemical and pharmacokinetic properties, such as highly ordered mesopores, high surface area and pore volume, tuneable pore size, stability, surface functionalisation, and biocompatibility. MSN-based nanocomposites have been used to deliver therapeutic molecules like insulin, GLP-1, exenatide, DPP-4 inhibitor and plasmid-containing GLP-1 genes for managing diabetes mellitus for the last decade. The functionalisation properties of MSNs make them substantially capable of the co-delivery, controlled delivery and stimuli-responsive delivery of antidiabetic drugs. This review focuses on the delivery of antidiabetic therapeutics with special emphasis on the functionalisation of MSNs and stimuli-responsive delivery.

A popular fermented soybean food of Northeast India exerted promising antihyperglycemic potential via stimulating PI3K/AKT/AMPK/GLUT4 signaling pathways and regulating muscle glucose metabolism in type 2 diabetes.

This study examined the antidiabetic efficacy of popular fermented soybean foods (FSF) of Northeast (NE) India. Results showed that among different FSF, aqueous extract of Hawaijar (AEH), a traditional FSF of Manipur, NE India, significantly augmented glucose utilization in cultured myotubes treated with high glucose (HG, 25 mM). Furthermore, AEH also upregulated glucose uptake, glucose-6-phosphate level, and phopho-PI3K/phospho-AKT/phospho-AMPK/GLUT4 protein expression in HG-treated myotubes. In vivo studies demonstrated that AEH supplementation (50, 100, or 200 mg/kg body weight/day, oral gavaging, 16 weeks) reduced body weight, fasting blood glucose, glycated hemoglobin, insulin resistance, and glucose intolerance in rats fed with high-fat diet (HFD). AEH supplementation stimulated phopho-PI3K/phospho-AKT/phospho-AMPK/GLUT4 signaling cascades involved in glucose metabolism of muscle tissues in diabetic rats. Chemical profiling of AEH (SDS-PAGE, immunoblotting, and HRMS) suggests the possible role of bioactive proteins/peptides and isoflavones underlying the antihyperglycemic potential AEH. Results from this study will be helpful for developing food-based prophylactics/therapeutics in managing hyperglycemia. PRACTICAL APPLICATIONS: Fermented soybean foods are gaining acceptance due to multiple health benefits. This study for the first time reports the antidiabetic potential of Hawaijar, an indigenous fermented soybean food of North-East India. Higher abundance of bioactive compounds (isoflavones and proteins/peptides) in Hawaijar may be responsible for the alleviation of impaired glucose metabolism associated with diabetes. The findings may be helpful for the development of a novel therapeutic to achieve better control of hyperglycemia and improve the lives of the patient population with diabetes.

Current perspectives on the anti-inflammatory potential of fermented soy foods.

Fermented soy foods (FSF) are gaining significant attention due to promising health benefits. In recent years, FSF are being studied extensively due to the presence of diverse functional ingredients including active isoflavones and peptides along with essential micronutrients. The process of fermentation is responsible for the enrichment of various bioactive principles in soy-based fermented foods and exclusion of some anti-nutrient factors which are found predominantly in raw soybeans. Emerging evidence suggests that FSF possess immense therapeutic potential against inflammation and associated pathological complications. Extracts prepared from various FSF (e.g. fermented soy paste, milk, and sauce) were found to exert promising anti-inflammatory effects in numerous in vitro and in vivo settings. Moreover, clinical findings highlighted an inverse relationship between consumption of FSF and the prevalence of chronic inflammatory disorders among the communities which habitually consume fermented soy products. Molecular mechanisms underlying the anti-inflammatory role of FSF have been delineated in many literatures which collectively suggest that FSF extracts have regulatory actions over the expression and/or activity of several proinflammatory cytokines, inflammatory mediators, oxidative stress markers, and some other factors involved in the inflammatory pathways. The present review discusses the anti-inflammatory effects of FSF with mechanistic insights based upon the available findings from cell culture, preclinical, and clinical investigations.

Homeopathic Medicines Used as Prophylaxis in Kolkata during the COVID-19 Pandemic: A Community-Based, Cluster-Randomized Trial.

INTRODUCTION: There is some evidence that homeopathic treatment has been used successfully in previous epidemics, and currently some countries are testing homeoprophylaxis for the coronavirus disease 2019 (COVID-19) pandemic. There is a strong tradition of homeopathic treatment in India: therefore, we decided to compare three different homeopathic medicines against placebo in prevention of COVID-19 infections. METHODS: In this double-blind, cluster-randomized, placebo-controlled, four parallel arms, community-based, clinical trial, a 20,000-person sample of the population residing in Ward Number 57 of the Tangra area, Kolkata, was randomized in a 1:1:1:1 ratio of clusters to receive one of three homeopathic medicines (Bryonia alba 30cH, Gelsemium sempervirens 30cH, Phosphorus 30cH) or identical-looking placebo, for 3 (children) or 6 (adults) days. All the participants, who were aged 5 to 75 years, received ascorbic acid (vitamin C) tablets of 500 mg, once per day for 6 days. In addition, instructions on healthy diet and general hygienic measures, including hand washing, social distancing and proper use of mask and gloves, were given to all the participants. RESULTS: No new confirmed COVID-19 cases were diagnosed in the target population during the follow-up timeframe of 1 month-December 20, 2020 to January 19, 2021-thus making the trial inconclusive. The Phosphorus group had the least exposure to COVID-19 compared with the other groups. In comparison with placebo, the occurrence of unconfirmed COVID-19 cases was significantly less in the Phosphorus group (week 1: odds ratio [OR], 0.1; 95% confidence interval [CI], 0.06 to 0.16; week 2: OR, 0.004; 95% CI, 0.0002 to 0.06; week 3: OR, 0.007; 95% CI, 0.0004 to 0.11; week 4: OR, 0.009; 95% CI, 0.0006 to 0.14), but not in the Bryonia or Gelsemium groups. CONCLUSION: Overall, the trial was inconclusive. The possible effect exerted by Phosphorus necessitates further investigation. TRIAL REGISTRATION: CTRI/2020/11/029265.

Antidiabetic potential of soy protein/peptide: A therapeutic insight.

Soybean (Glycine max) harbours high quality proteins which have been evident to exhibit therapeutic properties in alleviating many diseases including but not limited to diabetes and its related metabolic complications. Since diabetes is often manifested with hyperglycemia, impaired energy homeostasis and even low-grade chronic inflammation, plenty of information has raised the suggestion for soy protein supplementation in preventing and controlling these abnormalities. Moreover, clinical intervention studies have established a noteworthy correlation between soy protein intake and lower prevalence of diabetes. Besides soy protein, various soy-derived peptides also have been found to trigger antidiabetic response in different in vitro and in vivo models. Molecular mechanisms underlying the antidiabetic actions of soy protein and peptide have been predicted in many literatures. Results demonstrate that components of soy protein can act in diversified ways and modulate various cell signaling pathways to bring energy homeostasis and to regulate inflammatory parameters associated with diabetic pathophysiology. The main objective of the present review lies in a systemic understanding of antidiabetic role of soy protein and peptide in the context of impaired glucose and lipid metabolism, and inflammation.

Is diabetes mellitus a wrongdoer to COVID-19 severity?

The coronavirus disease 19 (COVID-19) has turned out to be a pandemic in short period of time due to the high transmissibility of its causative agent, severe acute respiratory syndrome coronavirus 2. Various reports have suggested the promising link between overexpression of angiotensin converting enzyme 2 (ACE2) and COVID-19 pathogenesis. The severity of COVID-19 pathophysiology is greatly depended on several comorbidities, like hypertension, diabetes mellitus (DM), respiratory and cardiovascular disease, out of which DM has emerged as a major risk factor. The current review focuses on the link among the expression of ACE2, use of ACE inhibitors (ACEIs) and angiotensin II type 1 receptor blockers (ARBs), and risk of COVID-19 pathogenesis in DM. The review also emphasizes on synergistic detrimental effect of DM and COVID-19 on the immune system in provoking uncontrolled cytokine storm which eventually leads to lethal consequences. Finally, several possible therapeutic strategies have been highlighted to reduce the excess of risk associated with COVID-19 in people with DM.

Chitosan: A promising therapeutic agent and effective drug delivery system in managing diabetes mellitus.

Chitosan, a promising carbohydrate biopolymer is gaining scientific attention in a wide range of biomedical applications due to its outstanding chemical and pharmacokinetic properties. Recently, various studies have demonstrated the beneficial activities of chitosan in protecting and proliferating pancreatic beta cells, lowering hyperglycemia, and preventing impaired lipid metabolism associated diabetes mellitus. Moreover, chitosan has also been used in formulating several types of micro/nano-carriers for the delivery of different antidiabetic drugs, like insulin, GLP1, exendin-4, DPP-4 inhibitor, and plasmid encoding insulin or GLP to reduce hyperglycemia. This review for the first time provides an overview of the currently available evidences on the potential benefits of chitosan in managing diabetes mellitus and also emphasizes on the chitosan-based micro/nano-carriers in delivery of various antidiabetic drugs via oral, nasal, and subcutaneous routes. The outcome of this review will be helpful for the development of a novel therapeutic to achieve better control of diabetes mellitus.

Daidzein, its effects on impaired glucose and lipid metabolism and vascular inflammation associated with type 2 diabetes.

Over the last decades, the incidence of type 2 diabetes (T2D) is increasing substantially. Emerging evidences from epidemiological studies have shown the association between higher intake of soy isoflavones and reduced risk of T2D and its associated health risks. Daidzein, a soy isoflavone, has been found to have a promising therapeutic potential in managing T2D pathophysiology. Fermented soybean is the major source of daidzein; however, it can also be formed via the consumption of its glycosylated moiety, daidzin with subsequent hydrolysis by intestinal bacterial enzyme. Many studies reported the prophylactic effect of daidzein on the improvement of hyperglycemia, insulin resistance, dislipidemia, obesity, inflammation, and other complications associated with T2D. The molecular mechanisms underlying the action of daidzein include diverged pathways where daidzein has been shown to interact with several signaling molecules and receptors to achieve desirable effect. Although the specific molecular mechanism is still elusive, further studies are thus needed to understand it in detail. In this review, we discuss the antidiabetic potential of daidzein with respect to the evidences from various clinical, preclinical, and cell culture studies and the underlying molecular mechanism in a precise way to have a comprehensive account on this isoflavone with promising therapeutic potential. © 2018 BioFactors, 44(5):407-417, 2018.