Ginsenoside Rc from Korean Red Ginseng (Panax ginseng C.A. Meyer) Attenuates Inflammatory Symptoms of Gastritis, Hepatitis and Arthritis.
Korean Red Ginseng (KRG) is an herbal medicine prescribed worldwide that is prepared from Panax ginseng C.A. Meyer (Araliaceae). Out of ginseng's various components, ginsenosides are regarded as the major ingredients, exhibiting anticancer and anti-inflammatory activities. Although recent studies have focused on understanding the anti-inflammatory activities of KRG, compounds that are major anti-inflammatory components, precisely how these can suppress various inflammatory processes has not been fully elucidated yet. In this study, we aimed to identify inhibitory saponins, to evaluate the in vivo efficacy of the saponins, and to understand the inhibitory mechanisms. To do this, we employed in vitro lipopolysaccharide-treated macrophages and in vivo inflammatory mouse conditions, such as collagen (type II)-induced arthritis (CIA), EtOH/HCl-induced gastritis, and lipopolysaccharide (LPS)/D-galactosamine (D-GalN)-triggered hepatitis. Molecular mechanisms were also verified by real-time PCR, immunoblotting analysis, and reporter gene assays. Out of all the ginsenosides, ginsenoside Rc (G-Rc) showed the highest inhibitory activity against the expression of tumor necrosis factor (TNF)-[Formula: see text], interleukin (IL)-1[Formula: see text], and interferons (IFNs). Similarly, this compound attenuated inflammatory symptoms in CIA, EtOH/HCl-mediated gastritis, and LPS/D-galactosamine (D-GalN)-triggered hepatitis without altering toxicological parameters, and without inducing gastric irritation. These anti-inflammatory effects were accompanied by the suppression of TNF-[Formula: see text] and IL-6 production and the induction of anti-inflammatory cytokine IL-10 in mice with CIA. G-Rc also attenuated the increased levels of luciferase activity by IRF-3 and AP-1 but not NF-[Formula: see text]B. In support of this phenomenon, G-Rc reduced TBK1, IRF-3, and ATF2 phosphorylation in the joint and liver tissues of mice with hepatitis. Therefore, our results strongly suggest that G-Rc may be a major component of KRG with useful anti-inflammatory properties due to its suppression of IRF-3 and AP-1 pathways.
* Department of Genetic Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea.|† Medical College, Qingdao University, Qingdao 266021, P. R. China.
Tao
T
Yu
‡ College of Veterinary Medicine, Kyungpook National University, Daegu 41566, Republic of Korea.
Man Hee
MH
Rhee
§ Department of Genetic Engineering, Sungkyunkwan University, 2066 Seobu-ro Jangan-gu, Suwon 16419, Republic of Korea.
Jongsung
J
Lee
¶ Institute of Traditional Medicine and Bioscience, Daejeon University, Daejeon 34520, Republic of Korea.
Seung Hyung
SH
Kim
* Department of Genetic Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea.|† Medical College, Qingdao University, Qingdao 266021, P. R. China.
Yanyan
Y
Yang
* Department of Genetic Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea.
Han Gyung
HG
Kim
* Department of Genetic Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea.
Yong
Y
Kim
∥ Department of Pharmacology, Inha University School of Medicine, Incheon 22212, Republic of Korea.
Chaekyun
C
Kim
** Korean Ginseng Corporation, Central Research Institute, Daejeon 34337, Republic of Korea.
Yi-Seong
YS
Kwak
†† Department of Veterinary Physiology, College of Veterinary Medicine, Chonbuk National University, Iksan 54596, Republic of Korea.
Jong-Hoon
JH
Kim
* Department of Genetic Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea.
Jae Youl
JY
Cho
D051698:Activating Transcription Factor 2; D000284:Administration, Oral; D000818:Animals; D001168:Arthritis / Q000188:drug therapy*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005756:Gastritis / Q000188:drug therapy*; D036145:Ginsenosides / Q000008:administration & dosage* / Q000302:isolation & purification / Q000494:pharmacology; D057809:HEK293 Cells; D006505:Hepatitis / Q000188:drug therapy*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D050838:Interferon Regulatory Factor-3; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008813:Mice, Inbred ICR; D005894:Panax / Q000737:chemistry*; D008517:Phytotherapy; D000067996:RAW 264.7 Cells
C497105:ATF2 protein, human; D051698:Activating Transcription Factor 2; D016207:Cytokines; D036145:Ginsenosides; C494232:IRF3 protein, human; D018836:Inflammation Mediators; D050838:Interferon Regulatory Factor-3; C494233:Irf3 protein, mouse; C044462:ginsenoside Rc
Anti-Inflammatory Effect; Arthritis; Gastritis; Ginsenoside Rc; Hepatitis; Panax ginseng C.A. Meyer