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

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-Guen Kwon, Young Myeong Kim

Research output: Contribution to journalArticle

12 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)515-524
Number of pages10
JournalJournal of Ethnopharmacology
Volume146
Issue number2
DOIs
Publication statusPublished - 2013 Mar 27

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Fruit
Atherosclerosis
Lipids
Gene Expression
High Fat Diet
Reactive Oxygen Species
Macrophages
Interleukin-1
Lipopolysaccharides
Serum
Genes
Heme Oxygenase-1
Rubus
Herbal Medicine
Lipid Peroxides
Traditional Medicine
Vascular Diseases
Cysteine
Glutamic Acid
Nitric Oxide

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Drug Discovery

Cite this

Kim, Sookon ; Kim, Chun Ki ; Lee, Kwang Soon ; Kim, Ji Hee ; Hwang, Haejun ; Jeoung, Dooil ; Choe, Jongseon ; Won, Moo Ho ; Lee, Hansoo ; Ha, Kwon Soo ; Kwon, Young-Guen ; Kim, Young Myeong. / Aqueous extract of unripe Rubus coreanus fruit attenuates atherosclerosis by improving blood lipid profile and inhibiting NF-κB activation via phase II gene expression. In: Journal of Ethnopharmacology. 2013 ; Vol. 146, No. 2. pp. 515-524.
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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.",
author = "Sookon Kim and Kim, {Chun Ki} and Lee, {Kwang Soon} and Kim, {Ji Hee} and Haejun Hwang and Dooil Jeoung and Jongseon Choe and Won, {Moo Ho} and Hansoo Lee and Ha, {Kwon Soo} and Young-Guen Kwon and Kim, {Young Myeong}",
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Aqueous extract of unripe Rubus coreanus fruit attenuates atherosclerosis by improving blood lipid profile and inhibiting NF-κB activation via phase II gene expression. / Kim, Sookon; Kim, Chun Ki; Lee, Kwang Soon; Kim, Ji Hee; Hwang, Haejun; Jeoung, Dooil; Choe, Jongseon; Won, Moo Ho; Lee, Hansoo; Ha, Kwon Soo; Kwon, Young-Guen; Kim, Young Myeong.

In: Journal of Ethnopharmacology, Vol. 146, No. 2, 27.03.2013, p. 515-524.

Research output: Contribution to journalArticle

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T1 - Aqueous extract of unripe Rubus coreanus fruit attenuates atherosclerosis by improving blood lipid profile and inhibiting NF-κB activation via phase II gene expression

AU - Kim, Sookon

AU - Kim, Chun Ki

AU - Lee, Kwang Soon

AU - Kim, Ji Hee

AU - Hwang, Haejun

AU - Jeoung, Dooil

AU - Choe, Jongseon

AU - Won, Moo Ho

AU - Lee, Hansoo

AU - Ha, Kwon Soo

AU - Kwon, Young-Guen

AU - Kim, Young Myeong

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N2 - 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.

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