Enhanced Drug Carriage Efficiency of Curcumin-Loaded PLGA Nanoparticles in Combating Diabetic Nephropathy via Mitigation of Renal Apoptosis.

Objectives: The Curcuma-derived diferuloylmethane compound CUR, loaded on Poly (lactide-co-glycolic) acid (PLGA) nanoparticles was utilized to combat DN-induced renal apoptosis by selectively targeting and modulating Bcl2. Methods: Upon in silico molecular docking and screening study CUR was selected as the core phytocompound for nanoparticle formulation. PLGA-nano-encapsulated-curcumin (NCUR) were synthesized following standard solvent displacement method. The NCUR were characterized for shape, size and other physico-chemical properties by Atomic Force Microscopy (AFM), Dynamic Light Scattering (DLS) and Fourier-Transform Infrared (FTIR) Spectroscopy studies. For in vivo validation of nephro-protective effects, Mus musculus were pre-treated with CUR at a dose of 50 mg/kg b.w. and NCUR at a dose of 25 mg/kg b.w. (dose 1), 12.5 mg/kg b.w (dose 2) followed by alloxan administration (100 mg/kg b.w) and serum glucose levels, histopathology and immunofluorescence study were conducted. Results: The in silico study revealed a strong affinity of CUR towards Bcl2 (dock score -10.94 Kcal/mol). The synthesized NCUR were of even shape, devoid of cracks and holes with mean size of ~80 nm having -7.53 mV zeta potential. Dose 1 efficiently improved serum glucose levels, tissue-specific expression of Bcl2 and reduced glomerular space and glomerular sclerosis in comparison to hyperglycaemic group. Conclusion: This study essentially validates the potential of NCUR to inhibit DN by reducing blood glucose level and mitigating glomerular apoptosis by selectively promoting Bcl2 protein expression in kidney tissue.

To explore the putative molecular targets of Diabetic Nephropathy and their inhibition utilizing potential phytocompounds.

BACKGROUND: This review critically addresses the putative molecular targets of Diabetic Nephropathy (DN) and screens effective phytocompounds that can be therapeutically beneficial, and highlights their mechanistic modalities of action. INTRODUCTION: DN has become one of the most prevalent complications of clinical hyperglycemia, with individual-specific variations in the disease spectrum that leads to fatal consequences. Diverse etiologies involving oxidative and nitrosative stress, activation of polyol pathway, inflammasome formation, Extracellular Matrix (ECM) modifications, fibrosis, and change in dynamics of podocyte functional and mesangial cell proliferation adds up to the clinical complexity of DN. Current synthetic therapeutics lacks target-specific approach, and is associated with the development of inevitable residual toxicity and drug resistance. Phytocompounds provides a vast diversity of novel compounds that can become an alternative therapeutic approach to combat the DN. METHOD: Relevant publications were searched and screened from research databases like GOOGLE SCHOLAR, PUBMED and SCISEARCH. Out of 4895 publications, the most relevant publications were selected and included in this article. RESULT: This study critically reviews over 60 most promising phytochemical and provides with their molecular targets, that can be of pharmacological significance in context to current treatment and concomitant research in DN. CONCLUSION: This review highlights those most promising phytocompounds that have the potential of becoming new safer naturally-sourced therapeutic candidates and demands further attention at clinical level.

Phyto-chlorophyllin Prevents Food Additive Induced Genotoxicity and Mitochondrial Dysfunction via Cytochrome c Mediated Pathway in Mice Model.

OBJECTIVES: The issue of food-additive-toxicity causing several health hazards needs to be therapeutically managed with an immediate effect. Alloxan, a food additive, is used for whitening and shining flour. It is capable of inducing genotoxicity, diabetes, and associated mitochondrial dysfunction. Therefore, to explore a non-toxic, phyto-based compound that can delay the onset of diabetes and prevent the multitude of damage associated, Chlorophyllin (CHL) was selected for our study, having been reported to exhibit anti-cancer, anti-diabetes, and antiinflammatory responses. Therefore, the objective of the present study is to evaluate the protective role of CHL in controlling genotoxicity, glucose imbalance, and associated cytochrome c mediated mitochondrial signaling dysfunction against food-additive-induced genotoxicity, diabetic state, and its complexities in mice model in vivo. METHODS: Mice were pre-treated with CHL through oral gavage before they were exposed to alloxan. Diabetic markers, anti-oxidant enzyme profile, chromosomal study, mitochondrial functioning factors, and expression of proteins were checked against food-additive injected mice. RESULTS: The results revealed that CHL pre-treatment could delay the onset of diabetes, restrict alloxan-induced elevation of blood glucose, reduce DNA-damage and chromosomal aberration, optimize enzymatic profile (glucokinase, pyruvate, insulin), and modulates protein expression (insulin, IRS1, IRS2, GLUT2). Further, CHL-pre-treatment could stabilize mitochondrial-membrane-potential, intracellular calcium ion, ATP/ADP ratio, ATPase activity, thereby maintaining optimum functioning of cytochrome-c, bcl2, and caspase3 mitochondrial protein. CONCLUSION: Therefore, the present study reports, for the first time, the screening of phytobased bioactive CHL for preventing/limiting the extent of food-additive-induced genotoxicity and mitochondrial dysfunction and serves as an advanced therapeutic tool in the management of diabetes.

Prevalence of hypertension and sociodemographic factors within the Scheduled Caste community of the District Nadia, West Bengal, India.

OBJECTIVE: The aim of this cross-sectional, community-based survey was to investigate the prevalence of hypertension, isolated systolic hypertension (ISH), isolated diastolic hypertension (IDH) and prehypertension according to sociodemographic features among the members of the households of the Scheduled Caste community of three selected villages (Chowgachha, Bagula and Chakdaha) of the District Nadia, West Bengal, India, in individuals aged 20-70 years. METHODS: A door-to-door survey was conducted by the author (MB). Detailed information was collected from participants who were interviewed using a systematic random sampling method and a pretested structured questionnaire. Standard instruments were used to obtain data on weight, height and blood pressure. Data were analysed using the z-test and chi-square test. RESULTS: Prevalence of prehypertension, hypertension, ISH and IDH in the study population was 19.28%, 17.93%, 8.07% and 6.72%, respectively. There was a significant development of hypertension with increasing age (p<0.001). Males (19.26%) showed a higher hypertensive rate than females (16.66%); however, this was not significant. In the three increasing body mass index (BMI) groups (<19.9, 20-24.9 and ≥25 kg/m(2)), the percentages of patients with hypertension were 19.27%, 23.23% and 29.62%, respectively. Hypertension was higher in the waist hip ratio (WHR) group of 0.90-0.99 (hypertension=23.12%) than the WHR group of 0.80-0.89 (hypertension=7.89%). BMI and WHR were significantly higher (p<0.001) in the hypertensive group compared with the non-hypertensive group. The percentage of patients with hypertension in three successive salt intake groups (3-6.9, 7-10.9 and >11 g/day) were 11.92%, 22.22% and 27.27%, respectively. CONCLUSIONS: The results of this investigation clearly indicate that there was a significant (p<0.001) role of dietary salt in the development of hypertension.