title: Petroleum ether sub-fraction of rosemary extract improves hyperlipidemia and insulin resistance by inhibiting SREBPs.
abstract: As a culinary and medicinal herb, rosemary is widely used. The present work aimed to investigate the effects of rosemary extracts on metabolic diseases and the underlying mechanisms of action. Liver cells stably expressing SREBP reporter were used to evaluate the inhibitory effects of different fractions of rosemary extracts on SREBP activity. The obese mice induced by Western-type diet were orally administered with rosemary extracts or vehicle for 7 weeks, the plasma and tissue lipids were analyzed. SREBPs and their target genes were measured by quantitative RT-PCR. We demonstrated that the petroleum ether sub-fraction of rosemary extracts (PER) exhibited the best activity in regulating lipid metabolism by inhibiting SREBPs, while water and n-BuOH sub-fraction showed the SREBPs agonist-effect. After PER treatment, there was a significant reduction of total SREBPs in liver cells. PER not only decreased SREBPs nuclear abundance, but also inhibited their activity, resulting in decreased expression of SREBP-1c and SREBP-2 target genes in vitro and in vivo. Inhibiting SREBPs by PER decreased the total triglycerides and cholesterol contents of the liver cells. In the mice fed with Western-type diet, PER treatment decreased TG, TC, ALT, glucose, and insulin in blood, and improved glucose tolerance and insulin sensitivity. Furthermore, PER treatment also decreased lipid contents in liver, brown adipose tissue, and white adipose tissue. Our results from the present study suggested that petroleum ether fraction of rosemary extracts exhibited the best potential of improving lipid metabolism by inhibiting SREBPs activity.
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Zhi-Shen
authors.initials: ZS
authors.lastname: Xie
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Ling-Jun
authors.initials: LJ
authors.lastname: Zhong
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Xiao-Meng
authors.initials: XM
authors.lastname: Wan
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Meng-Ning
authors.initials: MN
authors.lastname: Li
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China. Electronic address: liping2004@126.com.
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China; Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, China Pharmaceutical University, Nanjing 210009, China. Electronic address: xiaojunxu2000@163.com.
authors.forename: Xiao-Jun
authors.initials: XJ
authors.lastname: Xu
mesh_terms: D000473:Alkanes / Q000737:chemistry; D000818:Animals; D002784:Cholesterol / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006949:Hyperlipidemias / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010578:Petroleum / Q000032:analysis*; D010936:Plant Extracts / Q000008:administration & dosage* / Q000737:chemistry / Q000302:isolation & purification; D027542:Rosmarinus / Q000737:chemistry*; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism*; D051782:Sterol Regulatory Element Binding Protein 2 / Q000235:genetics / Q000378:metabolism*
chemical_list: D000473:Alkanes; D007328:Insulin; D010578:Petroleum; D010936:Plant Extracts; C497388:Srebf1 protein, mouse; C497391:Srebf2 protein, mouse; D051780:Sterol Regulatory Element Binding Protein 1; D051782:Sterol Regulatory Element Binding Protein 2; D002784:Cholesterol; C004544:naphtha
keywords: Hyperlipidemia; Insulin resistance; Rosemary; SREBPs