Caesalpinia sappan L. ameliorates hypercholesterolemia in C57BL/6 mice and suppresses inflammatory responses in human umbilical vein endothelial cells (HUVECs) by antioxidant mechanism.
Oxidative stress and inflammatory mediators were measured in the plasma and livers of C57BL/6 mice fed a high-cholesterol diet for 14 weeks and in cultured human umbilical vein endothelial cells (HUVECs). Some of the mice fed with the atherogenic diet received drinking water supplemented with 0.01 g of a 70% ethanol extract of Caesalpinia sappan L. (CSLE) per 20 g of body weight. Numerous parameters were determined: concentrations of total, high-, and low-density cholesterol; atherogenic index; plasma trolox equivalent antioxidant capacity (TEAC); levels of hepatic thiobarbituric acid reactive substances (TBARS) and protein carbonyls; and the activities of hepatic antioxidant enzymes, including Cu·Zn-SOD, Mn-SOD, glutathione peroxidase, glutathione reductase, and catalase. HUVECs were stimulated with tumor necrosis factor α (TNFα) and the expression of intracellular reactive oxygen species (ROS), lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), adhesion molecules, inhibitory κBα (IκBα), and nuclear factor κB (NFκB) were measured. Compared to mice fed a hypercholesterolemic diet alone, mice fed a hypercholesterolemic diet supplemented with CSLE exhibited decreased total plasma cholesterol and increased high-density lipoprotein cholesterol, and thus a lower atherogenic index. Furthermore, plasma TEAC and levels of hepatic TBARS and protein carbonyls were significantly decreased in CSLE-supplemented mice (P < 0.05), whereas all hepatic antioxidative indicators were significantly elevated (P < 0.05). In HUVECs stimulated with TNFα, CSLE significantly decreased the expression of intracellular ROS, LOX-1, and adhesion molecules; the degradation of IκBα; and the nuclear translocation of NFκB; in contrast, CSLE induced the expression of Nrf2 and HO-1 (P < 0.05 for all results).
Cardiovascular Medical Research Center and Department of Diagnostics, College of Oriental Medicine, Dongguk University, Sukjang-Dong 707, Gyeong-Ju 780-714, Gyeongbuk, Republic of Korea.
Min-Ja
MJ
Lee
Hye-Sook
HS
Lee
Hyun-Jung
HJ
Jung
Chang-Sub
CS
Lee
Jai-Eun
JE
Kim
Hyung-In
HI
Moon
Won-Hwan
WH
Park
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000975:Antioxidants / Q000378:metabolism; D001769:Blood / Q000187:drug effects / Q000378:metabolism; D001835:Body Weight; D029911:Caesalpinia / Q000737:chemistry*; D002470:Cell Survival / Q000187:drug effects; D004036:Diet, Atherogenic; D004365:Drugs, Chinese Herbal / Q000494:pharmacology* / Q000627:therapeutic use*; D004435:Eating; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000473:pathology / Q000517:prevention & control*; D020672:I-kappa B Proteins / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008055:Lipids / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009929:Organ Size; D018384:Oxidative Stress / Q000187:drug effects; D010088:Oxidoreductases / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D051127:Scavenger Receptors, Class E / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014471:Umbilical Veins / Q000166:cytology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D004365:Drugs, Chinese Herbal; C083487:I kappa B beta protein; D020672:I-kappa B Proteins; D008055:Lipids; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; C495635:NFE2L2 protein, human; C495137:OLR1 protein, human; D017382:Reactive Oxygen Species; D051127:Scavenger Receptors, Class E; D017392:Thiobarbituric Acid Reactive Substances; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D010088:Oxidoreductases; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1