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Curcumin-3,4-Dichloro Phenyl Pyrazole (CDPP) overcomes curcumin's low bioavailability, inhibits adipogenesis and ameliorates dyslipidemia by activating reverse cholesterol transport

Authors :
Kripa Shankar
Abhishek Gupta
Durgesh Kumar
Narender Tadigoppula
Sujith Rajan
Anil N. Gaikwad
R. J. Choudhary
Pragya Yadav
Vishal M. Balaramnavar
Rabi Sankar Bhatta
Salil Varshney
Ankita Srivastava
Vinay Kumar Singh
Muheeb Beg
Santosh Kumar
Source :
Metabolism. 73:109-124
Publication Year :
2017
Publisher :
Elsevier BV, 2017.

Abstract

Background Adipocyte dysfunction, obesity and associated metabolic disorders are of prime healthcare concern worldwide. Among available medications, natural products and inspired molecules hold 40% space in clinically prescribed medicines. In queue, this study overcomes the drawback of curcumin's low bioavailability with potent anti-adipogenic and anti-dyslipidemic activity. Methods To evaluate the role of CDPP on adipocyte differentiation, 3T3-L1 adipocytes were used as an in-vitro model. Flow cytometry was performed for cell cycle analysis. Syrian golden hamsters were used to study pharmacokinetic profile and dyslipidemic activity exhibited by CDPP. Result CDPP was found to be a potent inhibitor of adipogenesis in-vitro. It blocked mitotic clonal expansion by causing cell cycle arrest. CDPP showed marked improvement in gastrointestinal stability and bioavailability in-vivo as compared to curcumin. Administration of CDPP (100 mg/kg) significantly improved HFD induced dyslipidemic profile in hamsters and activated reverse cholesterol transport machinery. Conclusion CDPP could be used as a potential drug candidate against adipogenesis and dyslipidemia with enhanced gastrointestinal stability and bioavailability.

Details

ISSN :
00260495
Volume :
73
Database :
OpenAIRE
Journal :
Metabolism
Accession number :
edsair.doi.dedup.....685a0a7c9aca439ada5fa8c40cffdcad
Full Text :
https://doi.org/10.1016/j.metabol.2017.05.005