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Celastrol suppresses obesity process via increasing antioxidant capacity and improving lipid metabolism.

Abstract
High fat diet, as an important risk factor, plays a pivotal role in atherosclerotic process. Celastrol is one of the active triterpenoid compounds with antioxidative and anti-inflammatory characters. The aims of this study were to evaluate the effect of celastrol on weight, blood lipid and oxidative injury induced by high fat emulsion, and investigate its potential pharmacological mechanisms. Male Sprague-Dawley rats were fed with high fat emulsion for 6 wk to mimic high fat mediated oxidative injury. The effects of celastrol on weight and blood lipid were evaluated, and its mechanisms were disclosed by applying western blot, ELISA and assay kits. Long-term consumption of high fat emulsion could significantly increase weight by enhancing total cholesterol (TC), triacylglycerol (TG), apolipoprotein B (Apo B), low-density lipoprotein cholesterol (LDL-c) levels, attenuating ATP-binding cassette transporter A1 (ABCA1) expression, and decreasing the levels of high-density lipoprotein cholesterol (HDL-c) and apolipoprotein A-I (Apo A-I), and inhibit antioxidant enzymes activities, improve nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity. Comparing with model group, celastrol was able to effectively suppress weight and attenuate high fat mediated oxidative injury by improving ABCA1 expression, reducing the levels of TC, TG, LDL-c and Apo B in plasma, and increasing antioxidant enzymes activities and inhibiting NADPH oxidase activity, and decreasing the serum levels of Malondialdehyde (MDA) and reactive oxygen species in dose-dependent way. These data demonstrated that celastrol was able to effectively suppress weight and alleviate high-fat mediated cardiovascular injury via mitigating oxidative stress and improving lipid metabolism.
AuthorsChaoyun Wang, Chunfeng Shi, Xiaoping Yang, Ming Yang, Hongliu Sun, Chunhua Wang
JournalEuropean journal of pharmacology (Eur J Pharmacol) Vol. 744 Pg. 52-8 (Dec 05 2014) ISSN: 1879-0712 [Electronic] Netherlands
PMID25300680 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2014 Elsevier B.V. All rights reserved.
Chemical References
  • ATP Binding Cassette Transporter 1
  • Antioxidants
  • Apolipoprotein A-I
  • Apolipoproteins B
  • Lipoproteins, HDL
  • Lipoproteins, LDL
  • Pentacyclic Triterpenes
  • Reactive Oxygen Species
  • Triglycerides
  • Triterpenes
  • Malondialdehyde
  • NADP
  • celastrol
Topics
  • ATP Binding Cassette Transporter 1 (metabolism)
  • Animals
  • Antioxidants (metabolism)
  • Apolipoprotein A-I (metabolism)
  • Apolipoproteins B (metabolism)
  • Diet, High-Fat (adverse effects)
  • Lipid Metabolism (drug effects)
  • Lipoproteins, HDL (blood)
  • Lipoproteins, LDL (blood)
  • Male
  • Malondialdehyde (metabolism)
  • NADP (metabolism)
  • Obesity (blood, drug therapy, metabolism)
  • Oxidative Stress (drug effects)
  • Pentacyclic Triterpenes
  • Rats
  • Rats, Sprague-Dawley
  • Reactive Oxygen Species (metabolism)
  • Triglycerides (blood)
  • Triterpenes (pharmacology)

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