title: Coptis chinensis alkaloids exert anti-adipogenic activity on 3T3-L1 adipocytes by downregulating C/EBP-α and PPAR-γ.
abstract: Obesity is a complex, multifactorial, and chronic disease that increases the risk for type 2 diabetes, coronary heart disease and hypertension, and has become a major worldwide health problem. Developing novel anti-obesity drugs from natural products is a promising solution to the global health problem of obesity. While screening anti-obesity potentials of natural products, the methanol extract of the rhizome of Coptis chinensis (Coptidis Rhizoma) was found to significantly inhibit adipocyte differentiation and lipid contents in 3T3-L1 cells, as assessed by Oil-Red O staining. Five known alkaloids, berberine, epiberberine, coptisine, palmatine, and magnoflorine, were isolated from the n-BuOH fraction of the methanol extract of Coptidis Rhizoma. We determined the chemical structure of these alkaloids through comparisons of published nuclear magnetic resonance (NMR) spectral data. Furthermore, we screened these alkaloids for their ability to inhibit adipogenesis over a range of concentrations (12.5-50 μM). All five Coptidis Rhizoma alkaloids significantly inhibited lipid accumulation in 3T3-L1 cells without affecting cell viability in a concentration dependent manner. In addition, the five alkaloids significantly reduced the expression levels of several adipocyte marker genes including proliferator activated receptor-γ (PPAR-γ) and CCAAT/enhancer-binding protein-α (C/EBP-α). In the present study, we found that the isolated alkaloids inhibited adipogenesis in a dose-dependent manner in 3T3-L1 cells; this inhibition was attributed to their abilities to downregulate the protein levels of the adipocyte marker proteins PPAR-γ and C/EBP-α. Thus, these results suggest that Coptidis Rhizoma extract and its isolated alkaloids may be of therapeutic interest with respect to the treatment of obesity.
authors.affiliation: Department of Food and Life Science, College of Fisheries Science, Pukyong National University, Busan 608-737, Republic of Korea.
authors.forename: Jae Sue
authors.initials: JS
authors.lastname: Choi
authors.affiliation: Department of Microbiology, College of Natural Sciences, Pukyong National University, Busan 608-737, Republic of Korea.
authors.forename: Ji-Hye
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Food and Life Science, College of Fisheries Science, Pukyong National University, Busan 608-737, Republic of Korea.
authors.forename: Md Yousof
authors.initials: MY
authors.lastname: Ali
authors.affiliation: College of Pharmacy, Catholic University of Daegu, Gyeongbuk 712-702, Republic of Korea.
authors.forename: Byung-Sun
authors.initials: BS
authors.lastname: Min
authors.affiliation: Department of Microbiology, College of Natural Sciences, Pukyong National University, Busan 608-737, Republic of Korea. Electronic address: gundokim@pknu.ac.kr.
authors.forename: Gun-Do
authors.initials: GD
authors.lastname: Kim
authors.affiliation: Department of Food Science and Human Nutrition, Chonbuk National University, Jeonju 561-756, Republic of Korea. Electronic address: jungha@jbnu.ac.kr.
authors.forename: Hyun Ah
authors.initials: HA
authors.lastname: Jung
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects*; D050156:Adipogenesis / Q000187:drug effects*; D000470:Alkaloids / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000378:metabolism*; D039323:Coptis / Q000737:chemistry*; D015536:Down-Regulation; D051379:Mice; D047495:PPAR gamma / Q000378:metabolism*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D027343:Rhizome / Q000737:chemistry
chemical_list: D000470:Alkaloids; D022763:CCAAT-Enhancer-Binding Protein-alpha; D047495:PPAR gamma; D010936:Plant Extracts
keywords: 3T3-L1 cells; Adipocyte differentiation; C/EBP-α; Coptis chinensis; Obesity; PPAR-γ