Curcuma oil attenuates accelerated atherosclerosis and macrophage foam-cell formation by modulating genes involved in plaque stability, lipid homeostasis and inflammation.
In the present study, the anti-atherosclerotic effect and the underlying mechanism of curcuma oil (C. oil), a lipophilic fraction from turmeric (Curcuma longa L.), was evaluated in a hamster model of accelerated atherosclerosis and in THP-1 macrophages. Male golden Syrian hamsters were subjected to partial carotid ligation (PCL) or FeCl3-induced arterial oxidative injury (Ox-injury) after 1 week of treatment with a high-cholesterol (HC) diet or HC diet plus C. oil (100 and 300 mg/kg, orally). Hamsters fed with the HC diet were analysed at 1, 3 and 5 weeks following carotid injury. The HC diet plus C. oil-fed group was analysed at 5 weeks. In hyperlipidaemic hamsters with PCL or Ox-injury, C. oil (300 mg/kg) reduced elevated plasma and aortic lipid levels, arterial macrophage accumulation, and stenosis when compared with those subjected to arterial injury alone. Similarly, elevated mRNA transcripts of matrix metalloproteinase-2 (MMP-2), MMP-9, cluster of differentiation 45 (CD45), TNF-α, interferon-γ (IFN-γ), IL-1β and IL-6 were reduced in atherosclerotic arteries, while those of transforming growth factor-β (TGF-β) and IL-10 were increased after the C. oil treatment (300 mg/kg). The treatment with C. oil prevented HC diet- and oxidised LDL (OxLDL)-induced lipid accumulation, decreased the mRNA expression of CD68 and CD36, and increased the mRNA expression of PPARα, LXRα, ABCA1 and ABCG1 in both hyperlipidaemic hamster-derived peritoneal and THP-1 macrophages. The administration of C. oil suppressed the mRNA expression of TNF-α, IL-1β, IL-6 and IFN-γ and increased the expression of TGF-β in peritoneal macrophages. In THP-1 macrophages, C. oil supplementation prevented OxLDL-induced production of TNF-α and IL-1β and increased the levels of TGF-β. The present study shows that C. oil attenuates arterial injury-induced accelerated atherosclerosis, inflammation and macrophage foam-cell formation.
Pharmacology Division, CSIR-Central Drug Research Institute,B.S. 10/1, Sector 10, Sitapur Road, Jankipuram Extension,Lucknow226 031,India.
Vishal
V
Singh
Pharmacology Division, CSIR-Central Drug Research Institute,B.S. 10/1, Sector 10, Sitapur Road, Jankipuram Extension,Lucknow226 031,India.
Minakshi
M
Rana
Pharmacology Division, CSIR-Central Drug Research Institute,B.S. 10/1, Sector 10, Sitapur Road, Jankipuram Extension,Lucknow226 031,India.
Manish
M
Jain
Pharmacology Division, CSIR-Central Drug Research Institute,B.S. 10/1, Sector 10, Sitapur Road, Jankipuram Extension,Lucknow226 031,India.
Niharika
N
Singh
Division of Pharmaceutics, CSIR-Central Drug Research Institute,B.S. 10/1, Sector 10, Sitapur Road, Jankipuram Extension,Lucknow226 031,India.
Arshi
A
Naqvi
Division of Pharmaceutics, CSIR-Central Drug Research Institute,B.S. 10/1, Sector 10, Sitapur Road, Jankipuram Extension,Lucknow226 031,India.
Richa
R
Malasoni
Division of Pharmaceutics, CSIR-Central Drug Research Institute,B.S. 10/1, Sector 10, Sitapur Road, Jankipuram Extension,Lucknow226 031,India.
Anil Kumar
AK
Dwivedi
Pharmacology Division, CSIR-Central Drug Research Institute,B.S. 10/1, Sector 10, Sitapur Road, Jankipuram Extension,Lucknow226 031,India.
Madhu
M
Dikshit
Pharmacology Division, CSIR-Central Drug Research Institute,B.S. 10/1, Sector 10, Sitapur Road, Jankipuram Extension,Lucknow226 031,India.
Manoj Kumar
MK
Barthwal
D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000235:genetics / Q000378:metabolism; D050197:Atherosclerosis / Q000517:prevention & control*; D018955:CD36 Antigens / Q000235:genetics / Q000378:metabolism; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D006224:Cricetinae; D030024:Curcuma / Q000737:chemistry*; D059305:Diet, High-Fat; D005487:Foam Cells / Q000187:drug effects* / Q000378:metabolism; D006706:Homeostasis; D007249:Inflammation / Q000517:prevention & control; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000235:genetics / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D010938:Plant Oils / Q000494:pharmacology; D058226:Plaque, Atherosclerotic / Q000188:drug therapy* / Q000517:prevention & control; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D018955:CD36 Antigens; D002791:Cholesterol, Dietary; D007371:Interferon-gamma; D016753:Interleukin-10; D053583:Interleukin-1beta; D015850:Interleukin-6; D017493:Leukocyte Common Antigens; D008077:Lipoproteins, LDL; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D047493:PPAR alpha; D010936:Plant Extracts; D010938:Plant Oils; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C099252:oxidized low density lipoprotein; C012596:turmeric extract
Atherosclerosis; Curcuma oil; Inflammation; Macrophages; Oxidised LDL