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Aim. Stem cell therapy is one of the upcoming therapies for the treatment of diabetes. Discovery of potent differentiating agents is a prerequisite for increasing islet mass. The present study is an attempt to screen the potential of novel small biomolecules for their differentiating property into pancreatic islet cells using NIH3T3, as representative of extra pancreatic stem cells/progenitors. Methods. To identify new agents that stimulate islet differentiation, we screened various compounds isolated from Enicostemma littorale using NIH3T3 cells and morphological changes were observed. Characterization was performed by semiquantitative RT-PCR, Q-PCR, immunocytochemistry, immunoblotting, and insulin secretion assay for functional response in newly generated islet-like cell clusters (ILCC). Reversal of hyperglycemia was monitored after transplanting ILCC in STZ-induced diabetic mice. Results. Among various compounds tested, swertisin, an isolated flavonoid, was the most effective in differentiating NIH3T3 into endocrine cells. Swertisin efficiently changed the morphology of NIH3T3 cells from fibroblastic to round aggregate cell cluster in huge numbers. Dithizone (DTZ) stain primarily confirmed differentiation and gene expression studies signified rapid onset of differentiation signaling cascade in swertisin-induced ILCC. Molecular imaging and immunoblotting further confirmed presence of islet specific proteins. Moreover, glucose induced insulin release (in vitro) and decreased fasting blood glucose (FBG) (in vivo) in transplanted diabetic BALB/c mice depicted functional maturity of ILCC. Insulin and glucagon expression in excised islet grafts illustrated survival and functional integrity. Conclusions. Rapid induction for islet differentiation by swertisin, a novel herbal biomolecule, provides low cost and readily available differentiating agent that can be translated as a therapeutic tool for effective treatment in diabetes.

Enicostemma littorale (EL) Blume is one of the herbs widely used for treating and alleviating the effects of both type I and type II diabetes. However, lack of understanding of mechanism precludes the use of the herb and its molecules. In this study, we attempt to unravel the molecular mechanism of action of swertiamarin, a compound isolated form EL, by comparing its molecular effects with those of aqueous EL extract in alleviating the insulin resistance in type II diabetes. We further investigated hypolipidemic and insulin sensitizing effect of swertiamarin in experimentally induced noninsulin dependent diabetes mellitus (NIDDM) in rats. Swertiamarin (50 mg/kg) and aqueous extract (15 grams dried plant equivalent extract/kg) were administered to rats orally for 40 days and tight regulation of serum glucose, insulin, and lipid profile was found in both groups. Their mode of action was by restoring G6Pase and HMG-CoA reductase activities to normal levels and restoring normal transcriptional levels of PEPCK, GK, Glut 2, PPAR-γ, leptin, adiponectin, LPL, SREBP-1c, and Glut 4 genes. This suggests that both treatments increased insulin sensitivity and regulated carbohydrate and fat metabolism. This is the first report on the role of SM in regulating the PPARγ-mediated regulation of candidate genes involved in metabolism in peripheral tissues in vivo.

Problem statement: Malaria is a prevalent disease in India. The problem of drug resistance is worsening. Hence, new effective and affordable antimalarial drugs are very much needed. The long-established use of quinine and the more recent introduction of artemisinin as highly effective anti malarials demonstrate that plant species are an important resource for the discovery of new anti malarial agents. Approach: Majority of the plants belonging to Gentianaceae family were proven as good antimalarials containing swertiamarin as a common marker. Enicostemma littorale (Gentianaceae) is also known from traditional knowledge for treatment of visham jwara and is rich in swertiamarin amongst all of the plants belonging to same family. In view of this, initial screening had been undertaken. Our laboratory had also been working on the same for its antidiabetic activity. Results: This was first report to demonstrate anti plasmodial activity of Enicostemma littorale (Gentianaceae) against Plasmodium falciparum. Methanolic extract of plant and swertiamarin isolated from it showed promising results in vitro in schizont maturation inhibition assay having IC 50 of 529.045 and 12 µg mL −1 respectively. We also reported a simple and rapid method for isolation of swertiamarin which was applicable at commercial scale. Conclusion: The present study represented the potential antimalarial action of plant and its active phytoconstituent, may give new lead to researchers in field of antimalarial drug discovery.

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