title: Combination of spices and herbal extract restores macrophage foam cell migration and abrogates the athero-inflammatory signalling cascade of atherogenesis.
abstract: The trapping of lipid-laden macrophages in the arterial intima is a critical but reversible step in atherogenesis. However, information about possible treatments for this condition is lacking. Here, we hypothesized that combining the polyphenol-rich fractions (PHC) of commonly consumed spices (Allium sativum L (Liliaceae), Zingiber officinale R (Zingiberaceae), Curcuma longa L (Zingiberaceae)) and herbs (Terminalia arjuna (R) W & A (Combretaceae) and Cyperus rotundus L (Cyperaceae)) prevents foam cell formation and atherogenesis. Using an in vitro foam cell formation assay, we found that PHC significantly inhibited lipid-laden macrophage foam cell formation compared to the depleted polyphenol fraction of PHC (F-PHC). We further observed that PHC attenuated the LDL and LPS induced CD36, p-FAK and PPAR-γ protein expression in macrophages and increased their migration. NK-κB-DNA interaction, TNF-α, ROS generation, and MMP9 and MMP2 protein expression were suppressed in PHC-treated macrophages. The anti-atherosclerotic activity of PHC was investigated in a high fat- and cholesterol-fed rabbit model. The inhibition of foam cell deposition within the aortic intima and atheroma formation confirmed the atheroprotective activity of PHC. Therefore, we conclude that the armoury of polyphenols in PHC attenuates the CD36 signalling cascade-mediated foam cell formation, enhances the migration of these cells and prevents atherogenesis.
authors: Food and Drug Toxicology Research Centre, National Institute of Nutrition, (ICMR), Jamai Osmania, Hyderabad 500 007, India.
authors: Chetan
authors: C
authors: Nimgulkar
authors: Molecular Biology Unit, National Institute of Nutrition, (ICMR), Jamai Osmania, Hyderabad 500 007, India.
authors: Sudip
authors: S
authors: Ghosh
authors: Molecular Biology Unit, National Institute of Nutrition, (ICMR), Jamai Osmania, Hyderabad 500 007, India.
authors: Anand B
authors: AB
authors: Sankar
authors: Pathology Division, National Institute of Nutrition, (ICMR), Jamai Osmania, Hyderabad 500 007, India.
authors: Kumar P
authors: KP
authors: Uday
authors: Pathology Division, National Institute of Nutrition, (ICMR), Jamai Osmania, Hyderabad 500 007, India.
authors: M V
authors: MV
authors: Surekha
authors: Pathology Division, National Institute of Nutrition, (ICMR), Jamai Osmania, Hyderabad 500 007, India.
authors: P
authors: P
authors: Madhusudhanachary
authors: Food and Drug Toxicology Research Centre, National Institute of Nutrition, (ICMR), Jamai Osmania, Hyderabad 500 007, India.
authors: B R
authors: BR
authors: Annapurna
authors: Biophysics Division, National Institute of Nutrition, (ICMR), Jamai Osmania, Hyderabad 500 007, India.
authors: P
authors: P
authors: Raghu
authors: Food and Drug Toxicology Research Centre, National Institute of Nutrition, (ICMR), Jamai Osmania, Hyderabad 500 007, India. Electronic address: dineshantioxidant@gmail.com.
authors: Dinesh Kumar
authors: DK
authors: Bharatraj
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000188:drug therapy* / Q000378:metabolism; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects*; D002784:Cholesterol / Q000378:metabolism; D005487:Foam Cells / Q000187:drug effects* / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy* / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D010936:Plant Extracts / Q000494:pharmacology*; D058226:Plaque, Atherosclerotic / Q000188:drug therapy / Q000378:metabolism; D059808:Polyphenols / Q000737:chemistry; D011817:Rabbits; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D017365:Spices; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D017539:Tunica Intima / Q000187:drug effects / Q000378:metabolism
chemical_list: D008077:Lipoproteins, LDL; D010936:Plant Extracts; D059808:Polyphenols; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D002784:Cholesterol
keywords: Allium sativum; Anti-atherosclerotic; Macrophages foam cell; Polyphenols; Terminalia arjuna