Aqueous extract of unripe Rubus coreanus fruit attenuates atherosclerosis by improving blood lipid profile and inhibiting NF-κB activation via phase II gene expression.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE:

The fruit of Rubus coreanus has been used as a traditional herbal medicine for alleviation of inflammatory and vascular diseases in Asian countries.

AIM OF THE STUDY:

The anti-atherogenic effect of unripe Rubus coreanus fruit extract (URFE) and its underlying mechanism were analyzed in mice fed a high-fat diet (HFD) and in cell culture system.

MATERIALS AND METHODS:

Mouse was freely given HFD alone or supplemented with URFE for 14 weeks, followed by analysis of atherosclerotic lesions and serum lipid levels. For in vitro assay, macrophages were pretreated with URFE, followed by stimulation with lipopolysaccharide (LPS). Expression levels of inflammatory genes (TNF-α, IL-1β, and iNOS) and phase II genes (heme oxygenase-1, glutamate cysteine lygase, and peroxiredoxine-1) as well as intracellular reactive oxygen species (ROS) level and NF-κB activation pathway were analyzed in cultured macrophages as well as mouse sera and aortic tissues.

RESULTS:

URFE supplementation reduced HFD-induced atherosclerotic lesion formation which was correlated with decreased levels of lipids, lipid peroxides, and inflammatory mediators (TNF-α, IL-1β, and nitric oxide) in sera as well as suppression of inflammatory gene in aortic tissues. In addition, pre-treatment of macrophages with URFE also suppressed LPS-induced NF-κB activation, ROS production, and inflammatory and phase II gene expressions. Inhibition of phase II enzyme and protein activities attenuated the suppressive effects URFE on ROS production, NF-κB activation, and inflammatory gene expression.

CONCLUSION:

These results suggest that URFE attenuates atherosclerosis by improving blood lipid profile and inhibiting NF-κB activation via phase II antioxidant gene expression.

• Authors: Sookon Kim, Chun-Ki Kim, Kwang-Soon Lee, Ji-Hee Kim, Haejun Hwang, Dooil Jeoung, Jongseon Choe, Moo-Ho Won, Hansoo Lee, Kwon-Soo Ha, Young-Geun Kwon, Young-Myeong Kim
• Journal: Journal of ethnopharmacology (J Ethnopharmacol) Vol. 146 Issue 2 Pg. 515-24 (Mar 27 2013) ISSN: 1872-7573 [Electronic] Ireland
• PMID: 23353895 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Homeodomain Proteins
• Interleukin-1beta
• Membrane Proteins
• NF-E2-Related Factor 2
• NF-kappa B
• Nfe2l2 protein, mouse
• Plant Extracts
• Prrx1 protein, mouse
• Tumor Necrosis Factor-alpha
• Cholesterol
• Nitric Oxide Synthase Type II
• Nos2 protein, mouse
• Heme Oxygenase-1
• Hmox1 protein, mouse
• Glutamate-Cysteine Ligase

Topics

• Animals
• Aorta (metabolism)
• Atherosclerosis (drug therapy, genetics, metabolism)
• Cell Line
• Cholesterol (blood)
• Fruit
• Gene Expression Regulation (drug effects)
• Glutamate-Cysteine Ligase (genetics)
• Heme Oxygenase-1 (genetics)
• Homeodomain Proteins (genetics)
• Interleukin-1beta (metabolism)
• Male
• Membrane Proteins (genetics)
• Mice
• Mice, Inbred C57BL
• NF-E2-Related Factor 2 (metabolism)
• NF-kappa B (antagonists & inhibitors, metabolism)
• Nitric Oxide Synthase Type II (metabolism)
• Phytotherapy
• Plant Extracts (pharmacology, therapeutic use)
• Rosaceae
• Tumor Necrosis Factor-alpha (metabolism)