Protective effects of a compound herbal extract Tong Xin Luo on free fatty acid induced endothelial injury: Implications of antioxidant systemReport as inadecuate




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BMC Complementary and Alternative Medicine

, 8:39

First Online: 14 July 2008Received: 29 January 2008Accepted: 14 July 2008

Abstract

BackgroundTong-Xin-Luo TXL – a mixture of herbal extracts, has been used in Chinese medicine with established therapeutic efficacy in patients with coronary artery disease.

MethodsWe investigated the protective role of TXL extracts on endothelial cells injured by a known risk factor – palmitic acid PA, which is elevated in metabolic syndrome and associated with cardiovascular complications. Human aortic endothelial cells HAECs were preconditioned with TXL extracts before exposed to PA for 24 hours.

ResultsWe found that PA 0.5 mM exposure induced 73% apoptosis in endothelial cells. However, when HAECs were preconditioned with ethanol extracted TXL 100 μg-ml, PA induced only 7% of the endothelial cells into apoptosis. Using antibody-based protein microarray, we found that TXL attenuated PA-induced activation of p38-MAPK stress pathway. To investigate the mechanisms involved in TXL-s protective effects, we found that TXL reduced PA-induced intracellular oxidative stress. Through AMPK pathway, TXL restored the intracellular antioxidant system, which was depressed by the PA treatment, with an increased expression of thioredoxin and a decreased expression of the thioredoxin interacting protein.

ConclusionIn summary, our study demonstrates that TXL protects endothelial cells from PA-induced injury. This protection is likely mediated by boosting intracellular antioxidant capacity through AMPK pathway, which may account for the therapeutic efficacy in TXL-mediated cardiovascular protection.

AbbreviationsDAPI4-6- Diamidino-2-phenylindole dihydrochloride

AMPK5-AMP-activated protein kinase

BSABovine serum albumin

CADCoronary artery disease

DMSODimethyl sulfoxide

DTTDithiothreitol

EGM-2Endothelial cell growth medium-2

EGFREpidermal growth factor receptor

EGFEpidermal growth factor

EGTAEthylene glycol tetraacetic acid

EDTAEthylenediaminetetraacetic acid

FCS-EBMFetal calf serum-endothelial cell basic medium

FGF-BFibroblast growth factor B

FFAsFree fatty acids

HAECsHuman aortic endothelial cells

HAECsHuman aortic endothelial cells

IGF-1Insulin-like Growth Factor-1

JAKsJanus kinases

JNKJun N-terminal kinase

MEKKMAP kinase kinase kinase

MAPKMitogen-Activated Protein Kinase

PAPalmitic acid

PARPPoly ADP-ribose polymerase

PVDFPolyvinylidene Fluoride

PBSPphosphate buffered saline

PKCProtein kinase C

ROSReactive oxygen species

RIPKReceptor-interacting serine-threonine kinase

RSKRibosomal s6 kinase

STATSignal Transducers and Activators of Transcription

TUNELTerminal deoxynucleotidyltrasnferase-mediated dUTP nick-end labeling

TxnipThioredoxin interacting protein

TrxThioredoxin

TXLTong-Xin-Luo

TGF-βTransforming growth factor beta

VEGFVascular endothelial growth factor

Electronic supplementary materialThe online version of this article doi:10.1186-1472-6882-8-39 contains supplementary material, which is available to authorized users.

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Author: Lin Zhang - Yiling Wu - Zhenhua Jia - Yun Zhang - Hu Ying Shen - Xing Li Wang

Source: https://link.springer.com/







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