Compound K Inhibits the Lipopolysaccharide-Induced Inflammatory Responses in Raw 264.7 Cell Line and Zebrafish

Compound K, a major metabolite of ginsenosides Rb1, which is produced by human intestinal bacteria after oral administration, is one of the main pharmacologic compounds found in ginseng. In our previous study, we demonstrated that compound K inhibited the production of nitric oxide (NO) and prostagl...

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Main Authors: Su-Jung Ryu, Jia Choi, Jong-Seok Lee, Hyeon-Son Choi, Kye-Yoon Yoon, Ji-Hyun Hwang, Kui Jin Kim, Boo-Yong Lee
Format: Article
Language:English
Published: MDPI AG 2018-06-01
Series:Applied Sciences
Subjects:
Online Access:http://www.mdpi.com/2076-3417/8/6/924
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author Su-Jung Ryu
Jia Choi
Jong-Seok Lee
Hyeon-Son Choi
Kye-Yoon Yoon
Ji-Hyun Hwang
Kui Jin Kim
Boo-Yong Lee
author_facet Su-Jung Ryu
Jia Choi
Jong-Seok Lee
Hyeon-Son Choi
Kye-Yoon Yoon
Ji-Hyun Hwang
Kui Jin Kim
Boo-Yong Lee
author_sort Su-Jung Ryu
collection DOAJ
description Compound K, a major metabolite of ginsenosides Rb1, which is produced by human intestinal bacteria after oral administration, is one of the main pharmacologic compounds found in ginseng. In our previous study, we demonstrated that compound K inhibited the production of nitric oxide (NO) and prostaglandin E2 in lipopolysaccharide (LPS)-treated RAW264.7 cells. However, the mechanisms by which compound K may be effective against inflammation remain unknown. In the present study, compound K significantly inhibited LPS-induced NO production by suppression of inducible NO synthase (iNOS) in LPS-treated RAW264.7 cells. Compound K also inhibited LPS-induced cyclooxygenase-2 (COX-2) expression at both the mRNA and protein levels. It effectively suppressed both the release and mRNA expression levels of pro-inflammatory cytokines such as interleukin-1β (IL-1β) and IL-6. The anti-inflammatory effects of compound K appeared to occur via inhibition of LPS-induced phosphorylation of mitogen-activated protein kinases (MAPKs) and inhibition of NF-κB translocation from the cytosol to the nucleus by suppressing phosphorylation of inhibitory kappa B-α (IκB-α). Furthermore, we showed that compound K inhibited LPS-induced NO generation in an experimental zebrafish model. Considering these results, compound K could potentially be developed as a natural anti-inflammatory agent.
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spelling doaj.art-a6ce690cc1bf48598bb589a14aac8ed52022-12-22T03:18:45ZengMDPI AGApplied Sciences2076-34172018-06-018692410.3390/app8060924app8060924Compound K Inhibits the Lipopolysaccharide-Induced Inflammatory Responses in Raw 264.7 Cell Line and ZebrafishSu-Jung Ryu0Jia Choi1Jong-Seok Lee2Hyeon-Son Choi3Kye-Yoon Yoon4Ji-Hyun Hwang5Kui Jin Kim6Boo-Yong Lee7Department of Food Science and Biotechnology, College of Life Science, CHA University, Seongnam, Kyonggi 463-400, KoreaDepartment of Food Science and Biotechnology, College of Life Science, CHA University, Seongnam, Kyonggi 463-400, KoreaNational Institute of Biological Resources, Incheon 404-170, KoreaDepartment of Food and Nutrition, Seoul Women’s University 621, Hwarang-ro, Nowon-gu, Seoul 01797, KoreaDepartment of Food Science and Biotechnology, College of Life Science, CHA University, Seongnam, Kyonggi 463-400, KoreaDepartment of Food Science and Biotechnology, College of Life Science, CHA University, Seongnam, Kyonggi 463-400, KoreaDepartment of Food Science and Biotechnology, College of Life Science, CHA University, Seongnam, Kyonggi 463-400, KoreaDepartment of Food Science and Biotechnology, College of Life Science, CHA University, Seongnam, Kyonggi 463-400, KoreaCompound K, a major metabolite of ginsenosides Rb1, which is produced by human intestinal bacteria after oral administration, is one of the main pharmacologic compounds found in ginseng. In our previous study, we demonstrated that compound K inhibited the production of nitric oxide (NO) and prostaglandin E2 in lipopolysaccharide (LPS)-treated RAW264.7 cells. However, the mechanisms by which compound K may be effective against inflammation remain unknown. In the present study, compound K significantly inhibited LPS-induced NO production by suppression of inducible NO synthase (iNOS) in LPS-treated RAW264.7 cells. Compound K also inhibited LPS-induced cyclooxygenase-2 (COX-2) expression at both the mRNA and protein levels. It effectively suppressed both the release and mRNA expression levels of pro-inflammatory cytokines such as interleukin-1β (IL-1β) and IL-6. The anti-inflammatory effects of compound K appeared to occur via inhibition of LPS-induced phosphorylation of mitogen-activated protein kinases (MAPKs) and inhibition of NF-κB translocation from the cytosol to the nucleus by suppressing phosphorylation of inhibitory kappa B-α (IκB-α). Furthermore, we showed that compound K inhibited LPS-induced NO generation in an experimental zebrafish model. Considering these results, compound K could potentially be developed as a natural anti-inflammatory agent.http://www.mdpi.com/2076-3417/8/6/924compound KRAW264.7 cellzebrafishNF-κB(p-65)MAPK
spellingShingle Su-Jung Ryu
Jia Choi
Jong-Seok Lee
Hyeon-Son Choi
Kye-Yoon Yoon
Ji-Hyun Hwang
Kui Jin Kim
Boo-Yong Lee
Compound K Inhibits the Lipopolysaccharide-Induced Inflammatory Responses in Raw 264.7 Cell Line and Zebrafish
Applied Sciences
compound K
RAW264.7 cell
zebrafish
NF-κB(p-65)
MAPK
title Compound K Inhibits the Lipopolysaccharide-Induced Inflammatory Responses in Raw 264.7 Cell Line and Zebrafish
title_full Compound K Inhibits the Lipopolysaccharide-Induced Inflammatory Responses in Raw 264.7 Cell Line and Zebrafish
title_fullStr Compound K Inhibits the Lipopolysaccharide-Induced Inflammatory Responses in Raw 264.7 Cell Line and Zebrafish
title_full_unstemmed Compound K Inhibits the Lipopolysaccharide-Induced Inflammatory Responses in Raw 264.7 Cell Line and Zebrafish
title_short Compound K Inhibits the Lipopolysaccharide-Induced Inflammatory Responses in Raw 264.7 Cell Line and Zebrafish
title_sort compound k inhibits the lipopolysaccharide induced inflammatory responses in raw 264 7 cell line and zebrafish
topic compound K
RAW264.7 cell
zebrafish
NF-κB(p-65)
MAPK
url http://www.mdpi.com/2076-3417/8/6/924
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