title: Celastrus Orbiculatus Thunb. Reduces Lipid Accumulation by Promoting Reverse Cholesterol Transport in Hyperlipidemic Mice.
abstract: Previously, we found that Celastrus orbiculatus Thunb. (COT) decreases athero-susceptibility in lipoproteins and the aorta of guinea pigs fed a high-fat diet, and increases high-density lipoprotein (HDL). In the present study, we investigated the effect of COT in reducing lipid accumulation and promoting reverse cholesterol transport (RCT) in vivo and vitro. Healthy male mice were treated with high-fat diet alone, high-fat diet with COT (10.0 g/kg/d), or general fodder for 6 weeks. Serum levels of total cholesterol (TC), triglyceride (TG), HDL-C, non-HDL-C, and (3)H-cholesterol in plasma, liver, bile, and feces were determined. Pathological changes and the levels of TC and TG in liver were examined. The expression of hepatic genes and protein associated with RCT were analyzed. COT administration reduced lipid accumulation in the liver, ameliorated the pathological changes, and lessened liver injury, the levels of TG, TC, and non-HDL-C in plasma were decreased significantly, and COT led to a significant increase in plasma HDL-C and apolipoprotein A (apoA1). (3)H-cholesterol in plasma, liver, bile, and feces was also significantly increased in COT-treated mice compared to controls. Both mRNA and protein expression of SRB1, CYP7A1, LDLR, ATP-binding cassette transporters ABCA1, ABCG5, and LXRα were improved in COT-treated mice. An in vitro isotope tracing experiment showed that COT and its bioactive ingredients, such as celastrol, ursolic acid, oleanolic acid, and quercetin, significantly increased the efflux of (3)H-cholesterol. They also increased the expression of SRB1, ABCA1, and ABCG1 significantly in macrophages. Our findings provided a positive role of COT in reducing lipid accumulation by promoting RCT. These effects may be achieved by activating the SRB1 and ABC transporter pathway and promoting cholesterol metabolism via the CYP7A1 pathway in vivo. The effective ingredients in vitro are celastrol, ursolic acid, oleanolic acid, and quercetin.
authors.affiliation: Key Laboratory of Atherosclerosis in the Universities of Shandong and Institute of Atherosclerosis, Taishan Medical University, Tai'an, 271000, Shandong, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Atherosclerosis in the Universities of Shandong and Institute of Atherosclerosis, Taishan Medical University, Tai'an, 271000, Shandong, China.
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Si
authors.affiliation: Key Laboratory of Atherosclerosis in the Universities of Shandong and Institute of Atherosclerosis, Taishan Medical University, Tai'an, 271000, Shandong, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhai
authors.affiliation: Key Laboratory of Atherosclerosis in the Universities of Shandong and Institute of Atherosclerosis, Taishan Medical University, Tai'an, 271000, Shandong, China.
authors.forename: Shoudong
authors.initials: S
authors.lastname: Guo
authors.affiliation: Shandong Agricutural University, Tai'an, 271000, Shandong, China.
authors.forename: Jilong
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Atherosclerosis in the Universities of Shandong and Institute of Atherosclerosis, Taishan Medical University, Tai'an, 271000, Shandong, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Sang
authors.affiliation: Key Laboratory of Atherosclerosis in the Universities of Shandong and Institute of Atherosclerosis, Taishan Medical University, Tai'an, 271000, Shandong, China.
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Pang
authors.affiliation: Key Laboratory of Atherosclerosis in the Universities of Shandong and Institute of Atherosclerosis, Taishan Medical University, Tai'an, 271000, Shandong, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Atherosclerosis in the Universities of Shandong and Institute of Atherosclerosis, Taishan Medical University, Tai'an, 271000, Shandong, China.
authors.forename: Anbin
authors.initials: A
authors.lastname: Chen
authors.affiliation: Key Laboratory of Atherosclerosis in the Universities of Shandong and Institute of Atherosclerosis, Taishan Medical University, Tai'an, 271000, Shandong, China. sdyrx@163.com.
authors.forename: Shucun
authors.initials: S
authors.lastname: Qin
mesh_terms: D000818:Animals; D031247:Celastrus / Q000737:chemistry*; D002784:Cholesterol / Q000097:blood / Q000378:metabolism*; D008076:Cholesterol, HDL / Q000097:blood; D059305:Diet, High-Fat / Q000009:adverse effects*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects; D005819:Genetic Markers / Q000187:drug effects; D006949:Hyperlipidemias / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D050356:Lipid Metabolism / Q000187:drug effects*; D008297:Male; D051379:Mice; D010936:Plant Extracts / Q000008:administration & dosage* / Q000494:pharmacology; D021381:Protein Transport; D000067996:RAW 264.7 Cells; D014280:Triglycerides / Q000097:blood
chemical_list: D008076:Cholesterol, HDL; D005819:Genetic Markers; D010936:Plant Extracts; D014280:Triglycerides; D002784:Cholesterol
keywords: Celastrus orbiculatus Thunb.; Cholesterol efflux; Isotope tracing; Lipid accumulation; Reverse cholesterol transport