Ki Hoon Lee

A Lipid-Soluble Red Ginseng Extract Inhibits the Growth of Human Lung Tumor Xenografts in Nude Mice

Lipid-soluble ginseng extract was prepared by n-hexane extraction of red ginseng. BALB/c-nu mice were inoculated with human lung cancer (NCI-H460) cells to establish a human tumor xenograft model in nude mice, and the lipid-soluble ginseng extract was orally administered. The tumor inhibitory rates of the lipid-soluble ginseng extract at doses of 0.1, 0.3, and 1.0 g/kg/day were 18.9% (P < .05), 60.0% (P < .001), and 67.5% (P < .001), respectively. The oral administration of the lipid-soluble extract of red ginseng showed a potent anticancer effect in nude mice bearing human lung cancer cells in a dose-dependent manner without any apparent toxicity. This lipid-soluble ginseng extract is a potential nontoxic anticancer supplement for the prevention and intervention of lung tumor growth through an oral administration route.

Inhibition of human ovarian tumor growth by cytokine-induced killer cells.

Despite the recent improvement in the treatment of ovarian cancer, this disease is still leading cause of cancer death in women. In this study, the anti-tumor activity of cytokine-induced killer (CIK) cells against human ovarian cancer was evaluatedin vitro andin vivo. Although CD3+CD56+ cells were rare in fresh human peripheral blood mononuclear cells, they could expand more than 1,000-fold on day 14 in the presence of anti-CD3 antibody plus IL-2. At an effector-target cell ratio of 30:1, CIK cells destroyed 45% of SK-OV-3 human ovarian cancer cells, which was determined by the51Cr-release assay. In addition, CIK cells at a dose of 23 million cells per mouse inhibited 73% of SK-OV-3 tumor growth in nude mouse xenograft assay. This study suggests that CIK cells may be used as an adoptive immunotherapy for patients with ovarian cancer.

Inhibition of atopic dermatitis by topical application of silymarin in NC/Nga mice.

Silymarin has been known to inhibit chemical-induced irritant contact dermatitis. In the present study, we report that topical application of silymarin suppresses dust mite extract (DPE)-induced atopic dermatitis (AD) in NC/Nga mice. Repeated topical application of ears with DPE caused AD-like skin lesions in NC/Nga mice. However, silymarin reduced AD-like skin lesions in these mice, resulting in decreased ear swelling and leukocyte infiltration into the ear. Moreover, our results showed that mast cell infiltration into the ear was suppressed by silymarin treatment in DPE-treated NC/Nga mice. Silymarin also reduced plasma level of IL-4 and IgE in these mice. Further study demonstrated that the mRNA expression of IL-4 was increased and that of IFN-gamma was decreased by DPE treatment in the ears of NC/Nga mice. However, DPE-induced changes in IL-4 and IFN-gamma mRNA expression were reversed by silymarin. DPE-induced increase in TNF-alpha mRNA expression was also suppressed by silymarin treatment. The results presented in this report suggest that silymarin might be beneficial for the treatment of AD.

Improvement of high-fat diet-induced obesity by a mixture of red grape extract, soy isoflavone and l-carnitine: Implications in cardiovascular and non-alcoholic fatty liver diseases

In the present study, we examined the effect of a mixture of dietary components, including red grape extract, soy isoflavone and L-carnitine (RISC), on obesity. RISC substantially inhibited high-fat diet (HFD)-induced increase in body weight in a dose-dependent manner in C57BL/6 mice. The amount of subcutaneous and mesenteric fat was also significantly decreased by RISC treatment in HFD-fed C57BL/6 mice, whereas epididymal fat was not affected. Moreover, HFD-induced plasma leptin levels were down-regulated by RISC treatment. In these mice, RISC treatment significantly increased the plasma level of high density lipoprotein cholesterol without affecting the level of low density lipoprotein cholesterol and triglycerides. In addition, HFD-induced increase in liver weight and lipid accumulation in liver was significantly suppressed by RISC treatment in C57BL/6mice. Plasma level of glutamic-oxaloacetic transaminase and glutamic-pyruvic transaminase was also inhibited by RISC treatment. These results demonstrate that RISC suppresses HFD-induced obesity and suggest that RISC supplementation might be a promising adjuvant therapy for the treatment of obesity and its complications, such as cardiovascular and non-alcoholic fatty liver diseases.

Antiinflammatory activity of methanol extract isolated from stem bark of Magnolia kobus

The present study reports the antiinflammatory activity of a methanol extract isolated from the stem bark of Magnolia kobus (MK). MK potently inhibited lipopolysaccharide (LPS)‐induced production of nitric oxide and interleukin‐1β (IL‐1β) in RAW 264.7 cells, a murine macrophage‐like cell line. The secretion of tumor necrosis factor‐α (TNF‐α) was also suppressed in LPS‐stimulated RAW 264.7 cells although the magnitude of inhibition was weaker than that of nitric oxide and IL‐1β. The mRNA expressions of inducible nitric oxide synthase (iNOS), IL‐1β and TNF‐α were also suppressed by MK in LPS‐stimulated RAW 264.7 cells. Further study demonstrated that LPS‐induced DNA binding of AP‐1 and phosphorylation of c‐jun N‐terminal kinase (JNK) were inhibited by MK treatment in RAW 264.7 cells, whereas phosphorylation of p38 mitogen‐activated protein kinase was unaffected. Moreover, topical application of MK suppressed ear swelling in 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA)‐induced skin inflammation model. Collectively, these results suggest that MK exerts antiinflammatory effects in vitro and in vivo and this might be mediated, at least in part, by blocking AP‐1 and JNK activation. Copyright

Immunomodulating activity of a polysaccharide isolated from mori cortex radicis

The immunomodulating activity of a polysaccharide isolated fromMorus alba (PMA) root bark was examined in murine splenic lymphocytes. PMA enhanced proliferation of splenic lymphocytes in a synergistic manner in the presence of mitogens. However, PMA suppressed primary IgM antibody production, from B cells, which was activated with lipopolysaccharide, a polyclonal activator, or immunized with a T-cell dependent antigen sheep red blood cells. Our observations showed that the immunomodulating activity of PMA increased lymphocyte proliferation and that PMA decreased antibody production from B cells, which was distinct from those of other plant-originated polysaccharides.

Prevention of arthritic inflammation using an oriental herbal combination BDX-1 isolated fromAchyranthes bidentata andAtractylodes japonica

An oriental herbal combination (BDX-1) was isolated fromAchyranthes bidentata andAtractylodes japonica. We previously tested the clinical effectiveness of BDX-1 in rheumatoid arthritis (RA) patients and found that it has a beneficial therapeutic effect. Here, we provide experimental evidence for the effectiveness of BDX-1 on RA in murine models. The oral administration of BDX-1 was found to markedly inhibit collagen-induced arthritis, adjuvant-induced arthritis, and zymosan-induced inflammation. It also inhibited carrageenan-induced acute edema and acetic acid-induced writhing response. In addition, the biological activity of BDX-1 was found to be strongly increased by fermentation. Our results suggest that BDX-1 could be useful for the treatment of rheumatoid arthritis.

Widdrol induces apoptosis via activation of AMP-activated protein kinase in colon cancer cells

Widdrol, a natural sesquiterpene present in Juniperus sp., has been shown to exert anticancer and antifungal effects. Emerging evidence has suggested that AMP-activated protein kinase (AMPK), which functions as a cellular energy sensor, is a potential therapeutic target for human cancers. In this study, we found that AMPK mediates the anticancer effects of widdrol through induction of apoptosis in HT-29 colon cancer cells. We showed that widdrol induced the phosphorylation of AMPK in a dose- and time-dependent manner. The selective AMPK inhibitor compound C abrogated the inhibitory effect of widdrol on HT-29 cell growth. In addition, we demonstrated that widdrol induced apoptosis and this was associated with the activation of caspases, including caspase‑3/7 and caspase-9, in HT-29 cells. We also demonstrated that transfection of HT-29 cells with AMPK siRNAs significantly suppressed the widdrol-mediated apoptosis and the activation of caspases. However, cell cycle arrest induced by widdrol was not affected by transfection of HT-29 cells with AMPK siRNAs. Furthermore, widdrol inhibited HT-29 tumor growth in a human tumor xenograft model. Taken together, our results suggest that the anticancer effect of widdrol may be mediated, at least in part, by induction of apoptosis via AMPK activation.

A novel δ-lactam-based histone deacetylase inhibitor, KBH-A42, induces cell cycle arrest and apoptosis in colon cancer cells

In this study, we investigated the anti-tumor activity of KBH-A42 [N-hydroxy-3-(2-oxo-1-(3-phenylpropyl)-1,2,5,6-tetrahydropyridin-3-yl)propanamide], a novel synthetic histone deacetylase (HDAC) inhibitor. KBH-A42 inhibited a variety of HDAC isoforms in enzyme assays and suppressed growth of various cancer cell lines. Among the cell lines examined, colon cancer cells, including SW620, SW480 and HCT-15, were the cell types most sensitive to KBH-A42. KBH-A42 inhibition of cancer cell growth was comparable to or stronger than that of suberoylanilide hydroxamic acid (SAHA), a well-known HDAC inhibitor approved by the FDA to treat cutaneous T cell lymphomas. In SW620 cells, KBH-A42 increased the acetylation of histones, mediated cell cycle arrest (G1 arrest at low doses and G2 arrest at high doses), and induced apoptosis. The cell cycle arrest and apoptosis induced by KBH-A42 might be mediated through up-regulation of p21(Waf1) and activation of caspases, respectively. In addition, KBH-A42 inhibited SW620 tumor growth in a human tumor xenograft model. Taken together, our results indicate that KBH-A42 exerts an anti-tumor activity in vitro and in vivo and is a promising therapeutic candidate to treat human cancers.

A Combination of Grape Extract, Green Tea Extract and l-Carnitine Improves High-fat Diet-induced Obesity, Hyperlipidemia and Non-alcoholic Fatty Liver Disease in Mice

To develop a therapeutic agent for obesity‐related metabolic disorders, a mixture of dietary components was prepared, including grape extract, green tea extract and l‐carnitine (RGTC), and its effects on obesity, hyperlipidemia and non‐alcoholic fatty liver disease examined. The RGTC dramatically inhibited the high‐fat diet (HFD)‐induced increase in body weight and fat in C57BL/6 mice, whereas food consumption was not affected by RGTC treatment. The RGTC also concentration‐dependently suppressed the HFD‐induced increase in plasma lipids, such as low‐density lipoprotein cholesterol and triglycerides. In addition, increases in liver weight and liver steatosis were returned to normal by RGTC treatment in HFD‐fed C57BL/6 mice. The plasma levels of glutamic‐oxaloacetic transaminase and glutamic‐pyruvic transaminase were also significantly down‐regulated by RGTC treatment. These results suggest that RGTC suppressed HFD‐induced obesity, hyperlipidemia and non‐alcoholic fatty liver disease, suggesting that RGTC supplementation might be a promising adjuvant therapy for the treatment of these metabolic disorders. Copyright