title: N-butanol extracts of Morinda citrifolia suppress advanced glycation end products (AGE)-induced inflammatory reactions in endothelial cells through its anti-oxidative properties.
abstract: BACKGROUND
  Advanced glycation end products (AGEs), senescent macroprotein derivatives formed during a normal aging process and acceleratedly under diabetic conditions, play a role in atherosclerotic cardiovascular disease. AGEs cause endothelial cell (EC) damage, an initial trigger for atherosclerosis through the interaction with a receptor for AGEs (RAGE). We have previously shown that n-butanol extracts of Morinda citrifolia (noni), a plant belonging to the family Rubiaceae, block the binding of AGEs to RAGE in vitro. In this study, we examined the effects of n-butanol extracts of noni on reactive oxygen species (ROS) generation and inflammatory reactions on AGE-exposed human umbilical vein ECs (HUVECs).
  
  
  METHODS
  HUVECs were treated with 100 μg/ml AGE-bovine serum albumin (AGE-BSA) or non-glycated BSA in the presence or absence of 670 ng/ml n-butanol extracts of noni for 4 h. Then ROS generation and inflammatory and gene expression in HUVECs were evaluated by dihydroethidium staining and real-time reverse transcription-polymerase chain reaction analyses, respectively. THP-1 cell adhesion to HUVECs was measured after 2-day incubation of AGE-BSA or BSA in the presence or absence of 670 ng/ml n-butanol extracts of noni.
  
  
  RESULTS
  N-butanol extracts of noni at 670 ng/ml significantly inhibited the AGE-induced ROS generation and RAGE, intercellular adhesion molecule-1 and plasminogen activator inhibitor-1 gene expressions in HUVECs. AGEs significantly increased monocytic THP-1 cell adhesion to HUVECs, which was also prevented by 670 ng/ml n-butanol extracts of noni.
  
  
  CONCLUSIONS
  The present study demonstrated for the first time that N-butanol extracts of noni could suppress the AGE-induced inflammatory reactions in HUVECs through its anti-oxidative properties via blocking of the interaction of AGEs with RAGE. Inhibition of the AGE-RAGE axis by n-butanol extracts of noni may be a novel nutraceutical strategy for the treatment of cardiovascular disease.
authors.affiliation: Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, Kurume, 830-0011, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Ishibashi
authors.affiliation: Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, Kurume, 830-0011, Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Matsui
authors.affiliation: Morinda Worldwide Inc., Tokyo, 160-0023, Japan.
authors.forename: Fumiyuki
authors.initials: F
authors.lastname: Isami
authors.affiliation: Morinda Worldwide Inc., Tokyo, 160-0023, Japan.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Abe
authors.affiliation: Department of Chemistry, Kurume University School of Medicine, Kurume, 830-0011, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Sakaguchi
authors.affiliation: Department of Chemistry, Kurume University School of Medicine, Kurume, 830-0011, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Higashimoto
authors.affiliation: Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, Kurume, 830-0011, Japan. shoichi@med.kurume-u.ac.jp.
authors.forename: Sho-Ichi
authors.initials: SI
authors.lastname: Yamagishi
mesh_terms: D020001:1-Butanol / Q000737:chemistry; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D042783:Endothelial Cells / Q000187:drug effects*; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D032066:Morinda / Q000737:chemistry*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D017127:Glycation End Products, Advanced; D010936:Plant Extracts; D020001:1-Butanol
keywords: AGEs; Atherosclerosis; Oxidative stress; RAGE