N-butanol extracts of Morinda citrifolia suppress advanced glycation end products (AGE)-induced inflammatory reactions in endothelial cells through its anti-oxidative properties

Abstract

BackgroundAdvanced 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).MethodsHUVECs 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.ResultsN-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.ConclusionsThe 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.

Matrine‐Type Alkaloids Inhibit Advanced Glycation End Products Induced Reactive Oxygen Species‐Mediated Apoptosis of Aortic Endothelial Cells In Vivo and In Vitro by Targeting MKK3 and p38MAPK Signaling

“…ROS participates in many intracellular pathological changes. 6,7 In accord with our and other previous studies, ROS triggers programmed cell death through the mitochondrial pathway, death receptor pathway, and endoplasmic reticulum stress-mediated pathway. [8][9][10] Previous studies indicated that AGEs induced endothelial cell apoptosis by exacerbating ROSmediated apoptosis.…”

Morinda citrifolia noni water extract enhances innate and adaptive immune responses in healthy mice, ex vivo, and in vitro

“…Consistent with previous papers (Hirazumi & Furusawa, ; Nayak & Mengi, ; Palu et al, ), these results suggest that Mc‐eWE plays an immunostimulatory role in macrophages in vitro by inducing the mRNA expression of inflammatory mediators that are critical for protecting the body. In previous reports, however, solvent fractions such as ethanol, ethyl acetate, and butanol fractions of noni fruits reduced in vitro inflammatory responses in LPS‐stimulated RAW264.7 cells, H. pylori ‐infected AGS cells, and advanced glycation end product‐exposed human umbilical vein endothelial cells, and in vivo responses in dextran sulfate sodium‐induced colitis showing suppression of NO production and cytokine expression such as TNF‐α and IL‐1β (Coutinho de Sousa et al, ; Ishibashi et al, ; Kim et al, ; Liu et al, ; Nitteranon, Zhang, Darien, & Parkin, ). Although it is not fully elucidated yet, such opposite effects observed under inflammatory conditions could be due to different extraction or preparation methods such as simple squeezing versus sequential extraction, water versus organic solvents, or different origin of fruits such as Hawaii, Costa Rica, or Brazil to affect the composition of active components.…”

The Potential Health Benefits of Noni Juice: A Review of Human Intervention Studies

“…Several in vitro studies have indicated that noni fruit may be helpful in controlling the formation of advanced glycation end products (AGEs) and may subsequently reduce their adverse effects. An extract from noni fruit collected in French Polynesia prevented AGE-induced reactive oxygen species generation in human umbilical vein endothelial cells [ 63 ]. This extract also inhibited the in vitro formation of glucose-human serum albumin, glucose-collagen, and glucose-keratin AGEs as well exhibited AGE-crosslink breaking activity [ 64 ].…”