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

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 curc...

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Published in:Metabolism, clinical and experimental clinical and experimental, 2017-08, Vol.73, p.109-124
Main Authors: Gupta, Abhishek, Singh, Vinay Kumar, Kumar, Durgesh, Yadav, Pragya, Kumar, Santosh, Beg, Muheeb, Shankar, Kripa, Varshney, Salil, Rajan, Sujith, Srivastava, Ankita, Choudhary, Rakhi, Balaramnavar, Vishal M, Bhatta, Rabi, Tadigoppula, Narender, Gaikwad, Anil Nilkanth
Format: Article
Language:English
Subjects:
3T3 Cells
3T3-L1 adipocyte
Adipogenesis - drug effects
Animals
Anti-adipogenic
Biological Availability
Biological Transport, Active - drug effects
Cell Cycle Checkpoints - drug effects
Cholesterol - metabolism
Cricetinae
Curcumin - analogs & derivatives
Curcumin - pharmacokinetics
Curcumin - pharmacology
Curcumin - therapeutic use
Dyslipidemia
Dyslipidemias - drug therapy
Endocrinology & Metabolism
Mesocricetus
Mice
Pyrazoles - pharmacokinetics
Pyrazoles - pharmacology
Pyrazoles - therapeutic use
Reverse cholesterol transport
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Summary: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.
ISSN:0026-0495
1532-8600
DOI:10.1016/j.metabol.2017.05.005