TY - JOUR
T1 - Curcumin-3,4-Dichloro Phenyl Pyrazole (CDPP) overcomes curcumin's low bioavailability, inhibits adipogenesis and ameliorates dyslipidemia by activating reverse cholesterol transport
AU - Gupta, Abhishek
AU - Singh, Vinay Kumar
AU - Kumar, Durgesh
AU - Yadav, Pragya
AU - Kumar, Santosh
AU - Beg, Muheeb
AU - Shankar, Kripa
AU - Varshney, Salil
AU - Rajan, Sujith
AU - Srivastava, Ankita
AU - Choudhary, Rakhi
AU - Balaramnavar, Vishal M.
AU - Bhatta, Rabi
AU - Tadigoppula, Narender
AU - Gaikwad, Anil Nilkanth
N1 - Publisher Copyright:
© 2017 Elsevier Inc.
PY - 2017/8
Y1 - 2017/8
N2 - 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.
AB - 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.
KW - 3T3-L1 adipocyte
KW - Anti-adipogenic
KW - Dyslipidemia
KW - Reverse cholesterol transport
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U2 - 10.1016/j.metabol.2017.05.005
DO - 10.1016/j.metabol.2017.05.005
M3 - Article
C2 - 28732567
AN - SCOPUS:85020742545
SN - 0026-0495
VL - 73
SP - 109
EP - 124
JO - Metabolism: clinical and experimental
JF - Metabolism: clinical and experimental
ER -