Abhishek Gupta1, Vinay Kumar Singh2, Durgesh Kumar3, Pragya Yadav4, Santosh Kumar5, Muheeb Beg1, Kripa Shankar1, Salil Varshney3, Sujith Rajan3, Ankita Srivastava3, Rakhi Choudhary6, Vishal M Balaramnavar6, Rabi Bhatta5, Narender Tadigoppula7, Anil Nilkanth Gaikwad8. 1. Division of Pharmacology, CSIR-Central Drug Research Institute, Lucknow 226031, India. 2. Division of Medicinal and Process Chemistry, CSIR-Central Drug Research Institute, Lucknow 226031, India. 3. Division of Pharmacology, CSIR-Central Drug Research Institute, Lucknow 226031, India; Academy of Scientific and Innovative Research, New Delhi 110025, India. 4. Academy of Scientific and Innovative Research, New Delhi 110025, India; Division of Medicinal and Process Chemistry, CSIR-Central Drug Research Institute, Lucknow 226031, India. 5. Division of Pharmacokinetics, CSIR-Central Drug Research Institute, Lucknow 226031, India. 6. Global Institute of Pharmaceutical Education and Research, Jaspur Road, Kashipur 244713, India. 7. Division of Medicinal and Process Chemistry, CSIR-Central Drug Research Institute, Lucknow 226031, India. Electronic address: t_narendra@cdri.res.in. 8. Division of Pharmacology, CSIR-Central Drug Research Institute, Lucknow 226031, India. Electronic address: anil_gaikwad@cdri.res.in.
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.
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.