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Celastrus Orbiculatus Thunb. Reduces Lipid Accumulation by Promoting Reverse Cholesterol Transport in Hyperlipidemic Mice

  • Original Article
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Lipids

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 3H-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). 3H-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 3H-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.

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Abbreviations

COT:

Celastrus orbiculatus Thunb

RCT:

Reverse cholesterol transport

HDL-C:

High-density lipoprotein cholesterol

apoA1:

Apolipoprotein A

TC:

Total cholesterol

TG:

Triglyceride

SR-B1:

Scavenger receptor B1

ABCA1:

ATP-binding cassette transporter G1

ABCG1:

ATP-binding cassette transporter A1

CE:

Cholesterol ester

ABCG5:

ATP-binding cassette transporters G5

ABCG8:

ATP-binding cassette transporters G8

CYP7A1:

Cholesterol 7-alpha hydroxylase

SR-B1:

Scavenger receptor class B type 1

LXR:

Liver X receptor

TCMs:

Traditional Chinese medicines

AS:

Atherosclerosis

SDS-PAGE:

Sodium dodecyl sulfate polyacrylamide gel electrophoresis

CL:

Celastrol

RT:

Rutin

QC:

Quercetin

KF:

Kaempferol

OA:

Oleanolic acid

UA:

Ursolic acid

RT-PCR:

Real time PCR

LDL-R:

Low-density lipoprotein receptor

LSC:

Liquid scintillation counter

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Acknowledgments

This research was supported by financial donations from the Taishan Scholars Foundation of Shandong Province (200867), University of Science and Technology Plan Projects Fund of Shandong Province (J121M01), Taian City Technology Development Plan (201440774-03), Key development projects of Shandong province (2015GSF119008), and the Shandong Provincial Natural Science Fund (ZR2013HL063, ZR2013HQ014).

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    Authors and Affiliations

    1. Key Laboratory of Atherosclerosis in the Universities of Shandong and Institute of Atherosclerosis, Taishan Medical University, Tai’an, 271000, Shandong, China

      Ying Zhang, Yanhong Si, Lei Zhai, Shoudong Guo, Hui Sang, Xiaofei Pang, Xue Zhang, Anbin Chen & Shucun Qin

    2. Shandong Agricutural University, Tai’an, 271000, Shandong, China

      Jilong Zhao

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    1. Ying Zhang
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    Y. Zhang, Y. Si contributed equally to this study.

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    Zhang, Y., Si, Y., Zhai, L. et al. Celastrus Orbiculatus Thunb. Reduces Lipid Accumulation by Promoting Reverse Cholesterol Transport in Hyperlipidemic Mice. Lipids 51, 677–692 (2016). https://doi.org/10.1007/s11745-016-4145-x

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