PHARMACOEPIDEMIOLOGICAL SURVEY ON THE USE OF COSTUS PICTUS (INSULIN PLANT) IN CENTRAL KERALA

Objective: Costus pictus commonly known as spiral ginger or insulin plant is grown in gardens as ornamental plant especially in Kerala and used to control sugar levels. The objective of the present survey was to collect information on the use of this plant as a control measure for diabetes mellitus in a community in central Kerala.Methods: The study was conducted with the help of a semi-structured questionnaire. The questionnaire broadly included questions about knowledge of insulin plant, its use, quantity and frequency of use, the relation of plant material consumption with food intake, effects related to blood sugar level and other symptoms, any discomfort or complications after use among diabetic and normal people. The data obtained was quantitatively transferred to an excel sheet and statistical analysis was carried out.Results: From the survey, it can be inferred that Costus pictus is widely used to normalise their sugar level. People who are using insulin plant have not done any species identification scientifically. Due to lack of knowledge and difficulty in identification (especially in the non-flowering season), many people are using Costus speciosus without knowing its adverse effects and allergic reactions.Conclusion: From the survey, it can be concluded that Costus pictus is widely used in some part of the community in Kerala, to normalize their sugar level. It is warranted to increase the awareness in the community about different species of Costus plant and adverse effects associated with similar species

Identification and characterization of small-molecule inhibitors of Tie2 kinase

Angiopoietins and Tie2 receptor were recently identified as an endothelial cell-specific ligand-receptor system that is critical for vascular development and postnatal pathologic angiogenesis by mediating vascular integrity. In this study, we identified a series of small-molecule Tie2 inhibitors, which blocked Ang1-induced Tie2 autophosphorylation and downstream signaling with an IC 50 value at 0.3 μM. Further optimization yields improved selectivity, aqueous solubility, microsomal stability and cytochrome P450 profile for one of the compounds (compound 7). Both compound 1 and compound 7 inhibit endothelial cell tube formation. Furthermore, in a rat model of Matrigel-induced choroidal neovascularization, compound 7 significantly diminished aberrant vessel growth. Our findings demonstrate a potential clinical benefit by specifically targeting Tie2-mediated angiogenic disorders

Discovery of Pyrrolidine-Containing GPR40 Agonists: Stereochemistry Effects a Change in Binding Mode

A novel series of pyrrolidine-containing GPR40 agonists is described as a potential treatment for type 2 diabetes. The initial pyrrolidine hit was modified by moving the position of the carboxylic acid, a key pharmacophore for GPR40. Addition of a 4-<i>cis</i>-CF₃ to the pyrrolidine improves the human GPR40 binding <i>K</i>_i and agonist efficacy. After further optimization, the discovery of a minor enantiomeric impurity with agonist activity led to the finding that enantiomers <b>(</b><i><b>R,R</b></i><b>)-68</b> and <b>(</b><i><b>S,S</b></i><b>)-68</b> have differential effects on the radioligand used for the binding assay, with <b>(</b><i><b>R,R</b></i><b>)-68</b> potentiating the radioligand and <b>(</b><i><b>S,S</b></i><b>)-68</b> displacing the radioligand. Compound <b>(</b><i><b>R</b></i>,<i><b>R</b></i><b>)-68</b> activates both G_q-coupled intracellular Ca²⁺ flux and G_s-coupled cAMP accumulation. This signaling bias results in a dual mechanism of action for compound <b>(</b><i><b>R</b></i>,<i><b>R</b></i><b>)-68</b>, demonstrating glucose-dependent insulin and GLP-1 secretion in vitro. In vivo, compound <b>(</b><i><b>R</b></i>,<i><b>R</b></i><b>)-68</b> significantly lowers plasma glucose levels in mice during an oral glucose challenge, encouraging further development of the series