Vindoline Exhibits Anti-Diabetic Potential in Insulin-Resistant 3T3-L1 Adipocytes and L6 Skeletal Myoblasts.

Type 2 diabetes mellitus (T2DM) emerged as a major health care concern in modern society, primarily due to lifestyle changes and dietary habits. Obesity-induced insulin resistance is considered as the major pathogenic factor in T2DM. In this study, we investigated the effect of vindoline, an indole alkaloid of Catharanthus roseus on insulin resistance (IR), oxidative stress and inflammatory responses in dexamethasone (IR inducer)-induced dysfunctional 3T3-L1 adipocytes and high-glucose-induced insulin-resistant L6-myoblast cells. Results showed that dexamethasone-induced dysfunctional 3T3-L1 adipocytes treated with different concentrations of vindoline significantly enhanced basal glucose consumption, accompanied by increased expression of GLUT-4, IRS-1 and adiponectin. Similarly, vindoline-treated insulin-resistant L6 myoblasts exhibited significantly enhanced glycogen content accompanied with upregulation of IRS-1 and GLUT-4. Thus, in vitro studies of vindoline in insulin resistant skeleton muscle and dysfunctional adipocytes confirmed that vindoline treatment significantly mitigated insulin resistance in myotubes and improved functional status of adipocytes. These results demonstrated that vindoline has the potential to be used as a therapeutic agent to ameliorate obesity-induced T2DM-associated insulin resistance profile in adipocytes and skeletal muscles.

Curcumin incorporated titanium dioxide nanoparticles as MRI contrasting agent for early diagnosis of atherosclerosis- rat model.

MRI is an excellent diagnostic technique for atherosclerosis in a non-invasive manner. Application of contrasting agents can improve its contrast through ionic properties. Macrophages and foam cells produce MCP-1 antibody, the sign of development of atherosclerosis. The work aims to develop novel curcumin incorporated titanium dioxide nanoparticles (CTNPs) conjugated with MCP-1 antibody with the specific targeting capability to macrophage-foam cells as contrasting agent for MRI. In vivo toxicity studies of Curcumin, TNPs and CTNPs were also done in Sprague dawley rats by GGT and ALP assays and found to be normal in comparison with control. Histopathology of aorta confirmed that the compound could not elicit a toxic effect in the target organ. Rats were fed with a high cholesterol diet to develop atherosclerotic foam cells and confirmed by Sudan IV staining and serum cholesterol level. CTNP-MCP-1 was injected into animals through tail vein and MRI scanning was done, gave contrasting images of atherosclerotic aorta in comparison with normal. Thus CTNPs can be used as a cost-effective contrasting tool for diagnosis of atherosclerosis at early stages in view of clinical imaging.

In vitro and in vivo pharmacokinetics and toxicity evaluation of curcumin incorporated titanium dioxide nanoparticles for biomedical applications.

The present study deals with the preparation of stable Curcumin incorporated Titaniumdioxide Nanoparticles (CTNPs) by coprecipitation method for improving the bioavailability of curcumin and site specific drug delivery. The prepared nanoparticles were characterized by UV visible spectroscopy, FTIR, XRD, DLS, SEM and EDX. The characterization studies showed the interaction of curcumin to titanium dioxide nanoparticles. The average size of the prepared CTNPs was found to be ∼29 nm with zetapotential of-53.790 mV. In vivo and in vitro toxicological evaluations were carried out to determine the biological effect of CTNPs. In vitro parameters like cell viability, Lactate dehydrogenase (LDH) Assay, Neutral red uptake (NRU) assay and uptake of curcumin from CTNPs by the cells had been investigated. In vitro toxicity studies in THP1 and H9c2 cell lines showed that CTNPs are safe even at a dose of 200 ng. The in vivo part of the study was carried out with different doses of Curcumin (1 mg-20 mg/kg body weight), Titaniumdioxide Nanoparticles (TNPs) (1 mg-5 mg/kg Body weight) and CTNPs (5 mg-10 mg/kg Body weight) in Sprague dawley rat models to determine the pharmacokinetics and genotoxicity of the nanoparticle. This was done by analysing the parameters like SGPT, SGOT, LDH, hematological parameters and biodistribution of the nanomaterial at different organ sites. Genotoxicity of samples were done by comet assay on blood cells. No significant toxicity was observed in the parameters in samples treated group compared to controls. The overall results indicated that the CTNPs are nontoxic and is highly stable with improved site specific application compared to native curcumin and are suitable for biomedical applications.