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

Metabolism. 2017 Aug:73:109-124. doi: 10.1016/j.metabol.2017.05.005. Epub 2017 May 20.

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 (100mg/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.

Keywords: 3T3-L1 adipocyte; Anti-adipogenic; Dyslipidemia; Reverse cholesterol transport.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Adipogenesis / drug effects*
  • Animals
  • 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
  • Dyslipidemias / drug therapy*
  • Mesocricetus
  • Mice
  • Pyrazoles / pharmacokinetics
  • Pyrazoles / pharmacology*
  • Pyrazoles / therapeutic use

Substances

  • 4,4'-(2,2'-(1-(3,4-dichlorophenyl)-1H-pyrazole-3,5-diyl)bis(ethene-2,1-diyl)bis(2-methoxyphenol)
  • Pyrazoles
  • Cholesterol
  • Curcumin