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Interferon-γ-Mediated Natural Killer Cell Activation by an Aqueous Panax ginseng Extract.

Takeda K, Okumura K - Evid Based Complement Alternat Med (2015)

Bottom Line: This effect was only observed with the aqueous extract of P. ginseng.Interestingly, the ginsenosides Rb1 and Rg1 did not augment NK cell cytotoxicity.These results demonstrated that the aqueous P. ginseng extract augmented NK cell activation in vivo via an IFN-γ-dependent pathway.

View Article: PubMed Central - PubMed

Affiliation: Division of Cell Biology, Biomedical Research Center, Graduate School of Medicine, Juntendo University, Bunkyo-ku, Tokyo 113-8421, Japan ; Department of Biofunctional Microbiota, Graduate School of Medicine, Juntendo University, Bunkyo-ku, Tokyo 113-8421, Japan.

ABSTRACT
Panax ginseng extracts are used in traditional herbal medicines, particularly in eastern Asia, but their effect on natural killer (NK) cell activity is not completely understood. This study aimed to examine the effects of P. ginseng extracts on the cytotoxic activity of NK cells. We orally administered P. ginseng extracts or ginsenosides to wild-type (WT) C57BL/6 (B6) and BALB/c mice and to B6 mice deficient in either recombination activating gene 2 (RAG-2) or interferon-γ (IFN-γ). We then tested the cytotoxic activity of NK cells (of spleen and liver mononuclear cells) against NK-sensitive YAC-1 cells. Oral administration of P. ginseng aqueous extract augmented the cytotoxicity of NK cells in WT B6 and BALB/c mice and in RAG-2-deficient B6 mice, but not in IFN-γ-deficient B6 mice. This effect was only observed with the aqueous extract of P. ginseng. Interestingly, the ginsenosides Rb1 and Rg1 did not augment NK cell cytotoxicity. These results demonstrated that the aqueous P. ginseng extract augmented NK cell activation in vivo via an IFN-γ-dependent pathway.

No MeSH data available.


Related in: MedlinePlus

Activation of NK cytotoxicity by oral administration of aqueous P. ginseng extract. (a) WT B6 mice (n = 3 in each group) were administered with aqueous extract of P. ginseng (20 mg/kg; circle, 40 mg/kg; triangle, 100 mg/kg; diamond) on days -2 and -1 (closed symbols) or on day -1 (open symbols). Control mice (open square) (n = 3) were administered with the same volume (200 μL) of water on days -2 and -1. Liver and spleen MNCs were prepared and cytotoxicity was analyzed using NK-sensitive YAC-1 cells, at the indicated effector/target ratios. Data are shown as the mean ± SD of triplicate samples of all tested mice. Similar results were obtained in three independent experiments. ∗P < 0.05 as compared with the control at each effector/target ratio. (b) The populations of liver and spleen MNCs were analyzed by flow cytometry. MNC numbers and % of NK cells are indicated below every panel. Data are shown as mean ± SD of three mice in each group. Similar results were obtained in three independent experiments. (c) WT BALB/c and WT B6 mice (n = 3 in each group) were administered with aqueous extract of P. ginseng (50 mg/kg; closed square) or the same volume (200 μL) of water (open square) on days -2 and -1. Liver and spleen MNCs were prepared and cytotoxicity was analyzed using YAC-1 cells at the indicated effector/target ratios. Data are shown as mean ± SD of triplicate samples of all tested mice. Similar results were obtained in three independent experiments. ∗P < 0.05 as compared with the control at each effector/target ratio.
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fig2: Activation of NK cytotoxicity by oral administration of aqueous P. ginseng extract. (a) WT B6 mice (n = 3 in each group) were administered with aqueous extract of P. ginseng (20 mg/kg; circle, 40 mg/kg; triangle, 100 mg/kg; diamond) on days -2 and -1 (closed symbols) or on day -1 (open symbols). Control mice (open square) (n = 3) were administered with the same volume (200 μL) of water on days -2 and -1. Liver and spleen MNCs were prepared and cytotoxicity was analyzed using NK-sensitive YAC-1 cells, at the indicated effector/target ratios. Data are shown as the mean ± SD of triplicate samples of all tested mice. Similar results were obtained in three independent experiments. ∗P < 0.05 as compared with the control at each effector/target ratio. (b) The populations of liver and spleen MNCs were analyzed by flow cytometry. MNC numbers and % of NK cells are indicated below every panel. Data are shown as mean ± SD of three mice in each group. Similar results were obtained in three independent experiments. (c) WT BALB/c and WT B6 mice (n = 3 in each group) were administered with aqueous extract of P. ginseng (50 mg/kg; closed square) or the same volume (200 μL) of water (open square) on days -2 and -1. Liver and spleen MNCs were prepared and cytotoxicity was analyzed using YAC-1 cells at the indicated effector/target ratios. Data are shown as mean ± SD of triplicate samples of all tested mice. Similar results were obtained in three independent experiments. ∗P < 0.05 as compared with the control at each effector/target ratio.

Mentions: Oral administration of 20, 40, or 100 mg/kg aqueous P. ginseng extract to WT B6 mice for 2 days augmented the cytotoxicity of liver and spleen MNCs against YAC-1 cells (Figure 2(a)). Administration of 100 mg/kg aqueous P. ginseng extract for 1 day also significantly augmented the cytotoxic activity, although 1-day intake of 20 or 40 mg/kg of this extract did not augment cytotoxicity (Figure 2(a)). Neither the overall MNC numbers nor the NK cell populations in the liver and spleen significantly increased (Figure 2(b)). Oral administration of aqueous P. ginseng extract (50 mg/kg) augmented liver and spleen NK cell cytotoxicity in BALB/c and B6 mice, suggesting that there was no strain difference in this response (Figure 2(c)). None of the mice treated with oral aqueous P. ginseng extract showed signs of hepatotoxicity (assessed by measurement of serum alanine aminotransferase and aspartate aminotransferase) or systemic toxicity (assessed by observation of body weight, gross appearance, and behavior) (data not shown). These results showed that NK cytotoxicity, but not NK cell number, was increased by oral administration of aqueous P. ginseng extract.


Interferon-γ-Mediated Natural Killer Cell Activation by an Aqueous Panax ginseng Extract.

Takeda K, Okumura K - Evid Based Complement Alternat Med (2015)

Activation of NK cytotoxicity by oral administration of aqueous P. ginseng extract. (a) WT B6 mice (n = 3 in each group) were administered with aqueous extract of P. ginseng (20 mg/kg; circle, 40 mg/kg; triangle, 100 mg/kg; diamond) on days -2 and -1 (closed symbols) or on day -1 (open symbols). Control mice (open square) (n = 3) were administered with the same volume (200 μL) of water on days -2 and -1. Liver and spleen MNCs were prepared and cytotoxicity was analyzed using NK-sensitive YAC-1 cells, at the indicated effector/target ratios. Data are shown as the mean ± SD of triplicate samples of all tested mice. Similar results were obtained in three independent experiments. ∗P < 0.05 as compared with the control at each effector/target ratio. (b) The populations of liver and spleen MNCs were analyzed by flow cytometry. MNC numbers and % of NK cells are indicated below every panel. Data are shown as mean ± SD of three mice in each group. Similar results were obtained in three independent experiments. (c) WT BALB/c and WT B6 mice (n = 3 in each group) were administered with aqueous extract of P. ginseng (50 mg/kg; closed square) or the same volume (200 μL) of water (open square) on days -2 and -1. Liver and spleen MNCs were prepared and cytotoxicity was analyzed using YAC-1 cells at the indicated effector/target ratios. Data are shown as mean ± SD of triplicate samples of all tested mice. Similar results were obtained in three independent experiments. ∗P < 0.05 as compared with the control at each effector/target ratio.
© Copyright Policy - open-access
Related In: Results  -  Collection

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fig2: Activation of NK cytotoxicity by oral administration of aqueous P. ginseng extract. (a) WT B6 mice (n = 3 in each group) were administered with aqueous extract of P. ginseng (20 mg/kg; circle, 40 mg/kg; triangle, 100 mg/kg; diamond) on days -2 and -1 (closed symbols) or on day -1 (open symbols). Control mice (open square) (n = 3) were administered with the same volume (200 μL) of water on days -2 and -1. Liver and spleen MNCs were prepared and cytotoxicity was analyzed using NK-sensitive YAC-1 cells, at the indicated effector/target ratios. Data are shown as the mean ± SD of triplicate samples of all tested mice. Similar results were obtained in three independent experiments. ∗P < 0.05 as compared with the control at each effector/target ratio. (b) The populations of liver and spleen MNCs were analyzed by flow cytometry. MNC numbers and % of NK cells are indicated below every panel. Data are shown as mean ± SD of three mice in each group. Similar results were obtained in three independent experiments. (c) WT BALB/c and WT B6 mice (n = 3 in each group) were administered with aqueous extract of P. ginseng (50 mg/kg; closed square) or the same volume (200 μL) of water (open square) on days -2 and -1. Liver and spleen MNCs were prepared and cytotoxicity was analyzed using YAC-1 cells at the indicated effector/target ratios. Data are shown as mean ± SD of triplicate samples of all tested mice. Similar results were obtained in three independent experiments. ∗P < 0.05 as compared with the control at each effector/target ratio.
Mentions: Oral administration of 20, 40, or 100 mg/kg aqueous P. ginseng extract to WT B6 mice for 2 days augmented the cytotoxicity of liver and spleen MNCs against YAC-1 cells (Figure 2(a)). Administration of 100 mg/kg aqueous P. ginseng extract for 1 day also significantly augmented the cytotoxic activity, although 1-day intake of 20 or 40 mg/kg of this extract did not augment cytotoxicity (Figure 2(a)). Neither the overall MNC numbers nor the NK cell populations in the liver and spleen significantly increased (Figure 2(b)). Oral administration of aqueous P. ginseng extract (50 mg/kg) augmented liver and spleen NK cell cytotoxicity in BALB/c and B6 mice, suggesting that there was no strain difference in this response (Figure 2(c)). None of the mice treated with oral aqueous P. ginseng extract showed signs of hepatotoxicity (assessed by measurement of serum alanine aminotransferase and aspartate aminotransferase) or systemic toxicity (assessed by observation of body weight, gross appearance, and behavior) (data not shown). These results showed that NK cytotoxicity, but not NK cell number, was increased by oral administration of aqueous P. ginseng extract.

Bottom Line: This effect was only observed with the aqueous extract of P. ginseng.Interestingly, the ginsenosides Rb1 and Rg1 did not augment NK cell cytotoxicity.These results demonstrated that the aqueous P. ginseng extract augmented NK cell activation in vivo via an IFN-γ-dependent pathway.

View Article: PubMed Central - PubMed

Affiliation: Division of Cell Biology, Biomedical Research Center, Graduate School of Medicine, Juntendo University, Bunkyo-ku, Tokyo 113-8421, Japan ; Department of Biofunctional Microbiota, Graduate School of Medicine, Juntendo University, Bunkyo-ku, Tokyo 113-8421, Japan.

ABSTRACT
Panax ginseng extracts are used in traditional herbal medicines, particularly in eastern Asia, but their effect on natural killer (NK) cell activity is not completely understood. This study aimed to examine the effects of P. ginseng extracts on the cytotoxic activity of NK cells. We orally administered P. ginseng extracts or ginsenosides to wild-type (WT) C57BL/6 (B6) and BALB/c mice and to B6 mice deficient in either recombination activating gene 2 (RAG-2) or interferon-γ (IFN-γ). We then tested the cytotoxic activity of NK cells (of spleen and liver mononuclear cells) against NK-sensitive YAC-1 cells. Oral administration of P. ginseng aqueous extract augmented the cytotoxicity of NK cells in WT B6 and BALB/c mice and in RAG-2-deficient B6 mice, but not in IFN-γ-deficient B6 mice. This effect was only observed with the aqueous extract of P. ginseng. Interestingly, the ginsenosides Rb1 and Rg1 did not augment NK cell cytotoxicity. These results demonstrated that the aqueous P. ginseng extract augmented NK cell activation in vivo via an IFN-γ-dependent pathway.

No MeSH data available.


Related in: MedlinePlus