Scientific validation of the antimicrobial and antiproliferative potential of Clerodendrum serratum (L.) Moon, its phytoconstituents and their biosafety by acute oral toxicity study.

The screening of aqueous extract of Clerodendrum serratum revealed its broad-spectrum antimicrobial potential against Gram positive, Gram negative bacteria, and yeast. Optimizing the extraction strategies, revealed 15% concentration of aqueous extract prepared at 40 °C by extracting for 40 min, as optimum parameters and its statistical optimization by Box-Behnken design led to 1.16-1.35 folds enhancement in activity. Organic solvent extraction further improved the activity where methanol proved to be the best organic extractant which was effective against all the 13 pathogens tested with inhibition zone ranging from 14 to 32 mm. Minimum Inhibitory Concentration (MIC) study endorsed the methanolic extract to be the best organic extractant, as it showed the lowest MIC (0.5-10 mg/ml) in comparison to aqueous extract (1-10 mg/ml) as well as Partially Purified Phytoconstituents i.e., flavonoids (1-5 mg/ml), diterpenes (5-10 mg/ml) and cardiac glycosides (5-10 mg/ml). All these were found to be biosafe in both In-vitro (Ames and MTT assay) and In-vivo toxicity studies. Acute oral toxicity testing of flavonoids (2000 mg/ml) on Wistar rats did not reveal any significant change in relative organ weight, biochemical, hematological parameters and organs' architecture in comparison to control. Antiproliferative potential of flavonoids against human cancerous cell lines i.e., HeLa, HCT-15, and U87-MG, further increase the importance of this plant as a promising candidate for drug development. The overall study justified the medicinal importance of this plant.

Molecular Remodeling of the Insulin Receptor Pathway by Thiazolidinediones in Type 2 Diabetes Mellitus: A Brief Review.

Type 2 diabetes mellitus (T2DM) is characterized by abnormalities in carbohydrate, lipoprotein and lipid metabolism, leading to hyperglycemia and several other complications. Insulin is the major hormone regulating these facets by eliciting various biological responses through its receptor. Insulin exerts diverse effects on cells by targeting distinct functions such as gene expression, fatty acid synthesis, glucose transport and receptor translocation. Insulin mediates these effects through signaling pathways utilizing adapter molecules like small Gproteins, lipid and tyrosine kinases. The anomalous cell response in diabetic condition is due to altered expression/function of these molecules. Thiazolidinediones (TZD's), a class of oral hypoglycemic drugs, have shown to modify these responses, leading to insulin sensitizing effect(s). The TZD's are not only PPARγ agonists, but substantial insulin sensitizing activity is observed through its direct and indirect targets of the insulin receptor pathway, which contributes to its overall performance. TZD's alter(s) cell response via downstream players, primarily IRS, Akt/PKB, PKC, GLUT4, MEK, ERK and transcription factor PGC1α. Thus, this review will focus on the alteration(s) of these molecules in various cell types in diabetic condition and their regulation by TZD's. The physiological changes that occur at the molecular level in T2DM and their modulation by TZD's will provide insights into the key players involved and the potential drug targets for future drug development. The review further highlights the key markers to be evaluated in screening of any potential anti-diabetic agent, and to standardize therapy for T2DM based upon its modulation of the various signaling pathways.