title: Almonds inhibit dyslipidemia and vascular dysfunction in rats through multiple pathways.
abstract: BACKGROUND
  Almonds are reported to be protective against cardiovascular diseases (CVDs); however, the possible mode of action has only infrequently been explored.
  
  
  OBJECTIVE
  This study aimed at investigating the mechanistic basis for the benefits of almonds in atherosclerotic CVDs.
  
  
  METHODS
  Three studies in 3 groups of rats were designed with the use of tyloxapol (study 1), a high-fat diet (HFD; study 2), and white-flour fructose (WFF; study 3). In each of the studies, the first group acted as the control [administered saline in study 1 and fed a normal diet (ND) in studies 2 and 3]; the second and third groups were treated with tyloxapol in study 1, an HFD in study 2, and WFF in study 3. The third group in each study was also fed almonds (3 g/kg) for 4 wk, after which blood was collected for biochemical evaluation. Livers and aortas were isolated from the rats in studies 1 and 2 for enzyme assays and vascular analysis, respectively.
  
  
  RESULTS
  Almond supplementation significantly (P < 0.05) prevented hyperlipidemia in all of the rat models. Supplementation suppressed cholesterol synthesis, leading to a 65% inhibition of tyloxapol-induced activation of hepatic β-hydroxy-β-methylglutaryl coenzyme A reductase. The almond intervention inhibited by 56% the HFD-induced increase in serum concentrations of hepatic aminotransferases. Almonds also protected against an HFD-induced increase in uric acid (0.9-fold), phosphorus (1.1-fold), alkaline phosphatase (4.6-fold), and γ-glutamyltransferase (1-fold), with resultant concentrations that were not different from those in ND-fed rats (P > 0.05). Almonds partially restored the vascular reactivity of isolated aortas and prevented HFD-induced endothelial dysfunction by reducing inhibition of endothelial nitric oxide (NO) synthase and promoting NO release. The 70% decrease in HDL cholesterol that was observed in the WFF group was prevented by almond supplementation; serum and LDL cholesterol were also normalized.
  
  
  CONCLUSIONS
  The inhibition of de novo cholesterol synthesis, prevention of hepatic damage, and restoration of vascular function via the protection of endothelium and influence on the NO pathway are some of the mechanisms underlying the medicinal value of almonds in CVDs.
authors.affiliation: Natural Product Research Unit, Department of Biological and Biomedical Sciences, Aga Khan University, Karachi, Pakistan; and.
authors.forename: Humaira
authors.initials: H
authors.lastname: Jamshed
authors.affiliation: Natural Product Research Unit, Department of Biological and Biomedical Sciences, Aga Khan University, Karachi, Pakistan; and College of Health Sciences, Mekelle University, Mekelle, Ethiopia anwar.gilani@aku.edu.
authors.forename: Anwar H
authors.initials: AH
authors.lastname: Gilani
mesh_terms: D000818:Animals; D002784:Cholesterol / Q000096:biosynthesis; D004041:Dietary Fats / Q000008:administration & dosage / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D050171:Dyslipidemias / Q000178:diet therapy*; D004730:Endothelium, Vascular / Q000187:drug effects*; D005260:Female; D005433:Flour; D005632:Fructose; D015971:Gene Expression Regulation, Enzymologic; D008099:Liver / Q000201:enzymology; D008297:Male; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D011092:Polyethylene Glycols / Q000494:pharmacology; D027861:Prunus; D051381:Rats; D017207:Rats, Sprague-Dawley; D013869:Thiolester Hydrolases / Q000378:metabolism
chemical_list: D004041:Dietary Fats; D005632:Fructose; D011092:Polyethylene Glycols; D002784:Cholesterol; D052250:Nitric Oxide Synthase Type III; D013869:Thiolester Hydrolases; C032375:hydroxymethylgutaryl-CoA hydrolase; C016811:tyloxapol