Sumit Chaudhary, Aakanksha Dube, Vishal Kothari, Narsingh Sachan, Chandrashekhar Devidas Upasani
Department of Pharmacology, Faculty of pharmacy, Shri Neminath Jain Bramhacharyashram's Shriman Sureshdada Jain college of pharmacy Jain gurukul, Chandwad, Nashik, India.
European journal of pharmacology 2012 Jun 5Peroxisome proliferator-activated receptor (PPAR) γ is known to be a key regulator of insulin resistance. We characterized the pharmacological profiles of NS-1 chemically known as (5Z)-5-[4-hydroxy-3-methoxy-phenyl) methylene] thiazolidine-2, 4-dione), as a selective partial activator of PPARγ. In transient transactivation assay in NIH3T3 cells, NS-1 showed a partial activation against human PPARγ with an EC (50) of 0.91 μM without activating human PPARα and PPARδ. In adipocyte differentiation assay, NS-1 induced adipocyte differentiation, which was ~25-fold weaker inducer of GPDH activities than pioglitazone and also showed weak adipogenic activity in C3H10T1/2 pluripotent stem cells using Oil Red O staining. NS-1 showed good in vivo pharmacokinetic profiles in C57BL/6J mice at 30 mg/kg oral dose with Cmax-26 μM, terminal elimination half-life- 2.5h and bioavailability of 85%. Furthermore, NS-1 significantly improved hyperglycemia and insulin resistance in DIO animals when orally administered at a dose of 30 mg/kg/day for 45 days without significant weight gain. Overall, these studies suggest that NS-1 improves insulin resistance in such animal models through activation of PPARγ-mediated transcriptional activity and that it would be a new therapeutic candidate with potential for the treatment of type 2 diabetic patients. Copyright © 2012 Elsevier B.V. All rights reserved.
Sumit Chaudhary, Aakanksha Dube, Vishal Kothari, Narsingh Sachan, Chandrashekhar Devidas Upasani. NS-1: a novel partial peroxisome proliferator-activated receptor γ agonist to improve insulin sensitivity and metabolic profile. European journal of pharmacology. 2012 Jun 5;684(1-3):154-60
PMID: 22484334
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