Kim, Mi Jin;Kadayat, Taraman;Kim, Da Eun;Lee, Eung-Seok;Park, Pil-Hoon
Biomolecules & Therapeutics
/
v.22
no.5
/
pp.390-399
/
2014
Chalcones (1,3-diaryl-2-propen-1-ones), a flavonoid subfamily, are widely known for their anti-inflammatory properties. Propenone moiety in chalcones is known to play an important role in generating biological responses by chalcones. In the present study, we synthesized chalcone derivatives structurally modified in propenone moiety and examined inhibitory effect on nitric oxide (NO) production and its potential mechanisms. Among the chalcone derivatives used for this study, TI-I-174 (3-(2-Hydroxyphenyl)-1-(thiophen-3-yl)prop-2-en-1-one) most potently inhibited lipopolysaccharide (LPS)-stimulated nitrite production in RAW 264.7 macrophages. TI-I-174 treatment also markedly inhibited inducible nitric oxide synthase (iNOS) expression. However, TI-I-174 did not significantly affect production of IL-6, cyclooxygenase-2 (COX-2) and tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), implying that TI-I-174 inhibits production of inflammatory mediators in a selective manner. Treatment of macrophages with TI-I-174 significantly inhibited transcriptional activity of activator protein-1 (AP-1) as determined by luciferase reporter gene assay, whereas nuclear factor-${\kappa}B$ (NF-${\kappa}B$) activity was not affected by TI-I-1744. In addition, TI-I-174 significantly inhibited activation of c-Jun-N-Terminal kinase (JNK) without affecting ERK1/2 and p38MAPK, indicating that down-regulation of iNOS gene expression by TI-I-174 is mainly attributed by blockade of JNK/AP-1 activation. We also demonstrated that TI-I-174 treatment led to an increase in heme oxygenase-1 (HO-1) expression both at mRNA and protein level. Transfection of siRNA targeting HO-1 reversed TI-I-174-mediated inhibition of nitrite production. Taken together, these results indicate that TI-I-174 suppresses NO production in LPS-stimulated RAW 264.7 macrophages via induction of HO-1 and blockade of AP-1 activation.
Lee, Ki Man;Lee, Geum Seon;Shim, Hong;Oh, Se Koon;Park, Il Ho;Yim, Dongsool;Kang, Tae Jin
Korean Journal of Pharmacognosy
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v.43
no.4
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pp.323-327
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2012
Acne, also known as Acne vulgaris, is a common disorder of human skin involving the sebaceous gland and Propionibacterium acnes (P. acnes). The purpose of this study was to demonstrate whether anti-acne herbal complex (AAHC), a functional extract from herbal complex can be used for acne treatment as a natural product. We first demonstrated anti-acne activity of AAHC in mouse acne model. Acne was induced by injecting P. acnes on the backside $2{\times}10^7$ CFUs in ICR mice and then the mice were treated with AAHC by dermal application once daily. ACFREE$^{(R)}$ (clindamicin phosphate) was used as a positive control. Treatment with AAHC decreased the P. acnes-induced skin swelling and inflammation. AAHC treatment significantly decreased serum DHT concentration in acne-induced mice. Especially, treatment of 20% AACH in mice was more effected than 40%. We next evaluated the antimicrobial property of AAHC against P. acnes, Staphylcococcus aureus (S.aureus), and Escherichia coli (E. coli). Incubation of P. acnes, S. aureus, and E. coli with AAHC showed minimal inhibitory concentration (MIC) values against the bacterial growth lower. Alamar blue method was also carried for the antibacterial activity. It was effectively MIC level at 6.25% of P. acnes. AAHC effectively inhibited the growth of S. aureus and E. coli at 0.097% on MIC level, respectively. Our results showed the potential of using AAHC as an alternative treatment for antibiotic therapy of acne and the application of AAHC as a herbal medicine for acne treatment.
This study was performed to find out the inhibitory effect of Rhus Verniciflua extract on lipid peroxidation and inflammatory cytokines during endurance exercise training for 8 weeks in rats. For this study, Sprague-Dawley rats were divided into 4 groups; sedentary (SED), exercise training (TRA), RVS extract ingestion (RVE), and RVS extract ingestion and exercise training (RVE-TRA). TRA and RVE-TRA were trained on treadmill with increasing speed gradually and administered 10 mL/kg/d of Rhus Verniciflua extract orally to RVE and RVE-TRA. In order to analyze antioxidant function, blood SOD (superoxide dismutase), GSH-Px (glutathione peroxidase), and MDA (malondialdehyde) were examined. And, analysis of inflammatory cytokines were examined using IL-6 (interleukin-6), TNF-${\alpha}$ (tumor necrosis factor-alpha), CRP (C-reactive protein), and NO (nitric oxide). SOD in TRA was significantly higher than SED and RVE (p<0.05), and RVE-TRA was highest among the groups (p<0.05). The MDA content of TRA, RVE and RVE-TRA were significantly lower than SED. GSH-Px activity of SED was significantly lower than other groups (p<0.05). IL-6 and TNF-${\alpha}$ content of RVE and RVE-TRA were significantly lower than SED and TRA (p<0.05). CRP concentration of SED was the lowest among groups (p<0.05). Finally, NO concentration of SED and TRA were higher than RVE and RVE-TRA (p<0.05). These results suggested that it is efficient for rats to reduce lipid peroxidation and induce anti-inflammatory by taking RVS extract during exercise training. Afterwards, if studies on the properties of RVS extract can be made with various ways, use of Rhus Verniciflua trees might be made widely which are growing naturally in mountains in Korea.
Objective : This experiment was designed to investigate the effect of the CBD hot water extract & ultra-fine Powder on Alzheimer's Disease Model Induced by ${\beta}A$. Method : The effects of the CBD hot water extract on expression of interleukin-1 beta($IL-1{\beta}$), $TNF-{\alpha}$ mRNA and production of IL-6, $TNF-{\alpha}$ in BV2 microglial cell line treated by lipopolysacchaide(LPS). The effects of the CBD hot water extract & ultra-fine powder on (1) the behavior (2) expression of $IL-1{\beta}$, tumor necrosis factor-alpha($TNF-{\alpha}$), (3) the infarction area of the hippocampus in Alzheimer's diseased mice induced with ${\beta}A$ were investigated. Result : The CBD hot water extract suppressed the expression of $IL-1{\beta}$, $TNF-{\alpha}$ mRNA in BV2 microglia cell line treated with LPS. The CBD hot water extract significantly suppressed the production of $IL-1{\beta}$, $TNF-{\alpha}$ in BV2 microglial cell line treated with LPS. The CBD hot water extract & ultra-fine powder a significant inhibitory effect on the memory deficit was shown for the mice with Alzheimer's disease induced by ${\beta}A$ in the Morris water maze experiment, which measured step-through latency and distance movement-through latency. The CBD hot water extract & ultra-fine powder significantly suppressed the expression of $IL-l{\beta}$ and $TNF-{\alpha}$ protein in the microglial cell of mice with Alzheimer's disease induced by ${\beta}A$. The CBD hot water extract & ultra-fine powder suppressed the over-expression of AChE activity in the serum of the mice with Alzheimer's disease induced by ${\beta}A$. The CBD hot water extract & ultra-fine powder reduced infarction area of hippocampus, in the mice with Alzheimer's disease induced by ${\beta}A$. Conclusions : These results suggest that the CBD hot water extract & ultra-fine powder may be effective for the prevention and treatment of Alzheimer's disease. Investigation into the clinical use of the CBD hot water extract & ultra-fine powder for Alzheimer's disease is suggested for future research.
The anti-metastatic activity of water extract of Samguikoeuitang (WSGKE) consisting of Ginseng Radix, Angelicae Radix, Sophora flavescens and Coicis Semenwas examined. Ethanol extract of Samguikoeuitang (ESGKE) showed significant cytotoxicity against colon 26-M3.1 carcinoma cells, while WSGEK did not. However, WSGKE significantly increased the production of IL-6 and IL-12 in thioglycollate-induced macrophages from Balb/c mice, whereas ESGKE did not. WSGKE significantly increased natural killer (NK) cell cytotoxicity against effecter YAC-1 cells in an Effecter cells/Target ratio dependent manner. Also, WSGKE significantly suppressed lung metastasis after i.v. injection of colon26-M3.1 carcinoma cells. Inhibitory effect of WSGKE on lung metastasis totally abolished in NK cells-deficient mice by treatment with anti-asialo GM1 serum. In addition, the combination treatment of cisplatin and WSGKE (100 ${\mu}g$/mouse) prolonged the lifespan of mice inoculated by colon26-M3.1 cell. These findings suggest that WSGKE can inhibit lung metastasis and prolong life span via immunological enhancement as a Biological Response Modifier.
Journal of the Korean Society of Food Science and Nutrition
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v.34
no.6
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pp.784-789
/
2005
The inhibitory effects of hot water extracts of Rhus verniciflua Stokes pith and peel roasted at 170, 200 and $220^{\circ}C$ on lipid peroxidation, formation of DPPH free radicals and growth of four human cancer cells such as HepG2 (liver cancer), SNU-1 (stomach cancer), MCF-7 (breast cancer) and Widr (colon cancer) were examined. The antioxidant activities and growth inhibitory effects on cancer cells of hot water extracts of peel were higher than those of pith, and the activities were dose-dependent. The roasting temperature showing the highest antioxidant activities and growth inhibitory effects on cancer cells was in the range of $170\~200^{\circ}C$ The lipid peroxidation and formation of DPPH free radicals of hot water extracts of roasted pith and peel were inhibited to 50.9, $56.5\%\;and\;79.0,\;78.4\%$ at the concentration of $500\mu g/mL$, respectively. The growth inhibitory effects of roasted pith and peel on cancer cells were in the order of Widr (41.5, $36.0\%$) > HepG2 (61.5, $44.0\%$) > MCF-7 (92.0, $69.2\%$)> SNU-1 (100, $100\%$) cells at the concentration of $1,000\mu g/mL$ as compared with the control, respectively. These results suggest that roasted Rhus verniciflua Stokes could be an useful natural medicinal plant for colon cancer.
Objectives: This study was designed to investigate the anti-tumor metastasis by anti-inflammatory and innate immunomodulating effects of extracts of Jipae-san on cancer cells. Methods: Antimetastatic experiments were conducted in vivo mouse model by using 4T1 mouse mammary carcinoma cells. Cell viability of Jipae-san was tested with 4T1 mouse mammary carcinoma cells, colon 26-M3.1 carcinoma cells and macrophage. In addition expression of $TNF-{\alpha}$ and NO induced by LPS was measured after treating with Jipae-san. To observe innate immunomodulating effects of Jipae-san on macrophage, we measured $TNF-{\alpha}$, IL-12, IL-6 and MCP-1, respectively. Cell cytotoxicity was tested with the macrophage stimulated with Jipae-san and we evaluated the activation of $TNF-{\alpha}$ and NO. And the effect of Jipae-san on metastasis was measured without NK-cell using GM1 serum. Results: Intravenous inoculation of Jipae-san significantly inhibited metastasis of 4T1 mouse mammary carcinoma cells. In an in vitro cytotoxicity analysis, cell growth are closer to 100% less than $1,000{\mu}g/ml$ concentration. The expression of $TNF-{\alpha}$ and NO induced by LPS after treating Jipae-san was down regulated in dose-dependent manner. Level of cytokines such as $TNF-{\alpha}$, IL-12, IL-6 and MCP-1 of Jipae-san group were up regulated in compared to the control group. The macrophage stimulated with Jipae-san significantly inhibits the cancer cell at ratio of 10:1, 20:1. The activation of NO was significantly up regualted in a group of 5:1, 10:1, 20:1. The depletion of NK-cells by anti-asialo GM1 serum partly abolished the inhibitory effect of Jipae-san on tumor metastasis. Conclusions: Jipae-san appears to have considerable activity on the anti-metastasis by inflammation control and activation of innate immune system.
Lee, Ki Ho;Jang, Ji Hun;Woo, Kyeong Wan;Nho, Jong Hyun;Jung, Ho Kyung;Cho, Hyun Woo;Yong, Ju Hyun;An, Byeongkwan
Korean Journal of Pharmacognosy
/
v.50
no.1
/
pp.11-17
/
2019
Cassia tora L. have been used as a folk medicine in Korea. This study investigated anti-inflammatory effect of aurantio-obtusin isolated from C. tora. We isolated aurantio-obtusin from 50% ethanol extracts of C. tora L. We investigated the anti-inflammatory effects of aurantio-obtusin on the lipopolysaccharide (LPS)-stimulated inflammatory response in murine macrophage cell line (Raw 264.7). To investigate the cytotoxicity of aurantio-obtusin on RAW 264.7 cells, MTS assay was performed. RAW 264.7 cells were treated with aurantio-obtusin at different concentrations (12.5, 25, 50, $100{\mu}M$) for 30 h. The result showed that aurantio-obtusin had no cytotoxic effect in a concentration range of $12.5-100{\mu}M$. To determine the effect of aurantio-obtusin on LPS-induced NO production, the NO concentration measurement was performed. RAW 264.7 cells were treated with aurantio-obtusin at 12.5, 25, 50 and $100{\mu}M$ for 24 h, and the results showed that the NO production of aurantio-obtusin-treated cells compared to LPS alone treated group was significantly decreased in a dose-dependent manner. Pretreatment of aurantio-obtusin inhibited LPS-induced NO production in a dose-dependent manner. To find out inhibitory mechanisms of aurantio-obtusin on inflammatory mediators, we examined the $PGE_2$ pathways. As a result, $PGE_2$ were decreased in a dose-dependent manner by aurantio-obtusin. The release of interleukin-$1{\beta}$ (IL-$1{\beta}$) and IL-6 were also reduced. Moreover, aurantio-obtusin suppressed LPL-induced $I{\kappa}B-{\alpha}$ degradation. These results suggest that the down regulation of NO, $PGE_2$, IL-$1{\beta}$ and IL-6 expression by aurantio-obtusin are achieved by the downregulation of NF-${\kappa}B$ activity.
Objectives : Neuroinflammation is a common pathological mechanism of neurodegenerative diseases, and the development of therapeutic agents is urgently needed. Red ginseng has been known to be good for the immune stimulation in Eastern Asia. Although the immuno-stimulatory activity of red ginseng are already known, the neuro-protective effects of cultivated red ginseng with fermented complex mushroom-cereal mycelium (RGFM) have not been conducted. Thus, in this study, we tried to investigate the anti-neuroinflammatory effect of RGFM water extract on lipopolysaccharide (LPS) stimulated BV2 cells. Methods : BV2 cells were pretreated with RGFM 1 h prior to LPS exposure. To determine the neuro-protective effects of RGFM water extract, we measured the expression of inflammatory mediators including inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2 and nitric oxide (NO) and pro-inflammatory cytokines such as interleukin (IL)-1𝛽, IL-6 and tumor necrosis factor (TNF)-𝛼 in LPS-stimulated BV2 cells. In addition, to find out the regulatory mechanism of RGFM water extract, we assessed the protein levels of mitogen-activated protein kinases (MAPKs) and inhibitory 𝜅B𝛼 (I𝜅B𝛼) by western blotting. Results : In our study, treatment of RGFM reduced the mRNA expression of iNOS and COX-2 and suppressed NO production in LPS-stimulated BV2 cells. Additionally, the secretion of IL-1𝛽 and TNF-𝛼 but not IL-6 was significantly inhibited by RGFM. Furthermore, RGFM water extract inhibited the phosphorylation of c-Jun N-terminal kinase (JNK). Conclusions : Taken together, these findings suggest that RGFM water extract has a protective effect on neuroinflammation through inhibition of JNK.
This study was conducted to evaluate the antioxidative and anti-inflammatory effects of boiled pork powder (BPP) and hot water extract powder (HWEP) from 4 cuts of meat from Landrace × Yorkshire × Duroc (LYD). The highest DPPH radical scavenging activities determined were from BPP of Boston butt (13.65 M TE) and HWEP of loin (19.40 M TE) and ham (21.45 M TE). The 2,2-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radical scavenging activities of BPP from shoulder ham (39.28 M TE) and ham (39.43 M TE) were higher than those of other meat cuts, while HWEP of ham exhibited the highest ABTS radical scavenging activity. A higher oxygen radical absorbance capacity was determined for BPP from ham (198.35 M TE) and in HWEP from loin (204.07 M TE), Boston butt (192.85 M TE), and ham (201.36 M TE). Carnosine content of BPP and HWEP from loin and were determined to be 106.68 and 117.77 mg/g on a dry basis, respectively. The anserine content of BPP (5.26 mg/g, dry basis) and HWEP (6.79 mg/g, dry basis) of shoulder ham exhibited the highest value as compared to the extracts from the other meat cuts. The viability of RAW 264.7 cells was increased with increasing HWEP from loin and ham treatment. In addition, the expression of IL-6 and TNF-α was significantly reduced by HWEP from loin and ham, in a dose dependent manner. These results suggested that boiled pork and hot water extract of pork have antioxidative and cytokine inhibitory effects.
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