A novel mechanism of Korean red ginseng-mediated anti-inflammatory action via targeting caspase-11 non-canonical inflammasome in macrophages

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.

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ATF-2/CREB/IRF-3-targeted anti-inflammatory activity of Korean red ginseng water extract

Journal of Ethnopharmacology ◽

10.1016/j.jep.2014.04.008 ◽

2014 ◽

Vol 154 (1) ◽

pp. 218-228 ◽

Cited By ~ 33

Author(s):

Yanyan Yang ◽

Woo Seok Yang ◽

Tao Yu ◽

Gi-Ho Sung ◽

Kye Won Park ◽

...

Keyword(s):

Water Extract ◽

Inflammatory Activity ◽

Red Ginseng ◽

Korean Red Ginseng ◽

Anti Inflammatory

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Korean Red Ginseng Saponin Fraction Rich in Ginsenoside-Rb1, Rc and Rb2 Attenuates the Severity of Mouse Collagen-Induced Arthritis

Mediators of Inflammation ◽

10.1155/2014/748964 ◽

2014 ◽

Vol 2014 ◽

pp. 1-14 ◽

Cited By ~ 17

Author(s):

Mehari Endale ◽

Eun Ju Im ◽

Joo Young Lee ◽

Sung Dae Kim ◽

Taddesse Yayeh ◽

...

Keyword(s):

Inflammatory Responses ◽

Combined Therapy ◽

Cartilage Damage ◽

Serum Antibody ◽

Ginsenoside Rb1 ◽

Red Ginseng ◽

Korean Red Ginseng ◽

Ginseng Saponin ◽

Anti Inflammatory ◽

Saponin Fraction

Despite a multitude of reports on anti-inflammatory properties of ginseng extracts or individual ginsenosides, data on antiarthritic effect of ginseng saponin preparation with mixed ginsenosides is limited. On the other hand, a combined therapy of safe and inexpensive plant-derived natural products such as ginsenosides can be considered as an alternative to treat arthritis. Our previousin vitrodata displayed a strong anti-inflammatory action of red ginseng saponin fraction-A (RGSF-A). We, herein, report a marked antiarthritic property of RGSF-A rich in ginsenoside Rb1, Rc, and Rb2. Collagen-induced arthritic (CIA) mice were treated with RGSF-A or methotrexate (MTX) for 5 weeks. Joint pathology, serum antibody production and leukocye activation, cytokine production in the circulation, lymph nodes, and joints were examined. RGSF-A markedly reduced severity of arthritis, cellular infiltration, and cartilage damage. It suppressed CD3+/CD69+, CD4+/CD25+, CD8+T-cell, CD19+, B220/CD23+B-cell, MHCII+/CD11c+, and Gr-1+/CD11b+cell activations. It further suppressed anti-CII- or anti-RF-IgG/IgM, TNF-α, IL-1β, IL-17, and IL-6 secretions but stimulated IL-10 levels in the serum, joint, or splenocyte. RGSF-A attenuated arthritis severity, modified leukocyte activations, and restored cytokine imbalances, suggesting that it can be considered as an antiarthritic agent with the capacity to ameliorate the immune and inflammatory responses in CIA mice.

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Anti-inflammatory and antifatigue effect of Korean Red Ginseng in patients with nonalcoholic fatty liver disease

Journal of Ginseng Research ◽

10.1016/j.jgr.2015.07.006 ◽

2016 ◽

Vol 40 (3) ◽

pp. 203-210 ◽

Cited By ~ 32

Author(s):

Meegun Hong ◽

Yoon Hyeong Lee ◽

Seungwoo Kim ◽

Ki Tae Suk ◽

Chang Seok Bang ◽

...

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Nonalcoholic Fatty Liver Disease ◽

Fatty Liver Disease ◽

Red Ginseng ◽

Korean Red Ginseng ◽

Nonalcoholic Fatty Liver ◽

Anti Inflammatory

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Alleviation of Ulcerative Colitis Potentially through th1/th2 Cytokine Balance by a Mixture of Rg3-enriched Korean Red Ginseng Extract and Persicaria tinctoria

Molecules ◽

10.3390/molecules25225230 ◽

2020 ◽

Vol 25 (22) ◽

pp. 5230

Author(s):

Evelyn Saba ◽

Yuan Yee Lee ◽

Man Hee Rhee ◽

Sung-Dae Kim

Keyword(s):

Ulcerative Colitis ◽

Mitogen Activated Protein Kinase ◽

Raw 264.7 Cells ◽

Enzyme Linked Immunosorbent Assay ◽

Red Ginseng ◽

Korean Red Ginseng ◽

Ginseng Extract ◽

Anti Inflammatory

Ginseng is a vastly used herbal supplement in Southeast Asian countries. Red ginseng extract enriched with Rg3 (Rg3-RGE) is a formula that has been extensively studied owing to its various biological properties. Persicaria tinctoria (PT), belonging to the Polygonaceae family, has also been reported for its anti-inflammatory properties. Ulcerative colitis (UC) is inflammation of the large intestine, particularly in the colon. This disease is increasingly common and has high probability of relapse. We investigated, separately and in combination, the effects of Rg3-RGE and PT using murine exemplary of UC induced by DSS (Dextran Sulfate Sodium). For in vitro and in vivo experiments, nitric oxide assay, qRT-Polymerase Chain Reaction (PCR), Western blot, ulcerative colitis introduced by DSS, Enzyme Linked Immunosorbent Assay (ELISA), and flow cytometry analysis were performed. The results obtained demonstrate that treatment with Rg3-RGE + PT showed synergism to suppress inflammation (in vitro) in RAW 264.7 cells via mitogen-activated protein kinase and nuclear factor κB pathways. Moreover, in C57BL/6 mice, this mixture exhibits strong anti-inflammatory effects in restoring colon length, histopathological damage, pro-inflammatory mediators, and cytokines amount, and decreasing levels of NLRP3 inflammasome (in vivo). Our results recommend that this mixture can be used for the prevention of UC as a prophylactic/therapeutic supplement.

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