• The Korea Journal of Herbology
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• v.27 no.6
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• pp.115-122
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• 2012

Objectives : This study evaluated activities and ingredient contents concerning extracts according to extraction solvents of Insampaedok-san (IS, Renshen bai du-san). Methods : The herbal constituents of IS were extracted with water and 70% ethanol at $100^{\circ}C$ for 2 hr. Using the HPLC system, the six ingredient contents of different solvent extracts of IS were analyzed. The nitric oxide (NO), prostaglandin $E_2$ ($PGE_2$) production and proinflammatory cytokines were measured in RAW264.7 cells stimulated with lipopolysaccharide (LPS). The macrophage-derived chemokine (MDC/CCL22) and regulated on activation normal T-cell expression and secreted (RANTES/CCL5) production were measured in HaCaT and BEAS-2B cells stimulated tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) and interferon-${\gamma}$ (IFN-${\gamma}$). The activities of glycerol-3-phosphate dehydrogenase (GPDH) and leptin level were measured in 3T3-L1 cells. Results : The calibration curves showed good linearity ($r^2$=1.0000) for different concentration ranges. The contents of liquiritin, naringin, hesperidin, neohesperirin and glycyrrizin in 70% ethanol extracts of IS were relatively higher than that of water extract, however the content of ferulic acid in 70% ethanol and water extract of IS were similar. The extraction solvents of water and 70% ethanol were evaluated inhibitory effect on the production of NO, $PGE_2$, TNF-${\alpha}$ and IL-6 in RAW 264.7 cells. Their extractions were inhibitory effect on production of MDC/CCL22 and RANTES/CCL5 in HaCaT cell and BEAS-2B cell, respectively. In addition, evaluated reduced on GPDH activity and leptin level in 3T3-L1 preadipocyte cell. Conclusions : Our results suggest that IS extracts were inhibitory effects of disease such as inflammation, allergies and obesity.

• Proceedings of the KOR-BRONCHOESO Conference
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• 1982.05a
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• pp.17.1-17
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• 1982

In 1965, Rosenberg reported that platinum compounds not only inhibit growth and cell division of E. coli but also has anti-tumor activity. Since then, through animal and clinical experiments by Welsch(1971), Speer(1972), Rossof(1972), Hill(1974), and Wittes(1975), it was proved that Cis-platinum has excellent supressive effects on malignant tumor, especially on head and neck cancer. Accordingly, Cis-platinum is now widely used, sometimes without any other durg, or sometimes with Bleomycin and Methotrexate etc. Inspite of the strong anticancer effect, the use of Cis-platinum is quite often discouraged because of the reports that Cis-platinum causes auditory impairment at high frequencies above the speech range due to inner ear damage and irreversible change in the renal tubules. Since Kohonen et al(1965), Standnicki et al(1974) reported that Cisplatinum has toxic effects at the basal turn of the cochlea using guinea pig, many studies on ototoxicity after infusion of Cis-platinum have been carried out using animals. But the studies on ototoxicity in human beings can hardly be found except in reports by Piel et al(1974) and Hong et al (1979). So the authors did a study which tried to clarify the ototoxic effect by comparing the hearing level after infusion of Cis-plastinum with the hearing level before infusion of Cis-plastinum in 30 patients who was treated with Cis-platinum and admitted to the dept. of otolaryngology of Yonsei University Hospital during 2 years and a half from July. 1979 to March. 1982 and the following results were obtained. 1) The results of auditory evaluation, using the pure tone average, hearing loss of 4kHz and 8kHz, Speech Reception Threshold, PB score, SISI showed that the difference of dosage does not change the hearing level after infusion of Cis-platinum and before infusion of Cis-platinum. 2) Cis-platinum had no effect on the hearing level of patients with conductive hearing loss, or with sensorineural hearing loss, as well as with normal hearing level. 3) The infusion of Cis-platinum did not cause any change in creatinine clearance, creatinine, uric acid, but only one case showed that Cis-platinum caused severe nephrotoxicity. 4) The infusion of Cis-plastinum did not cause any change in hemoglobin, leukocyte count, platelet count and there was no correlation with the amount of infusion. 5) To see the side effect of hydration practiced with the infusion of Cis-platinum, the electrolytes, particularly the K level in the serum was measured. But the results did not show any change. 6) Judging from the results of this study mentioned above, ototoxicity caused by infusion of Cis-platinum can be prevented by sufficient hydration. Also the results might say that the appropriate method of infusion of Cis-platinum might be effective in the patients with head and neck cancer who had sensorineural hearing loss for whom the infusion of Cis-platinum has been absolutely cotraindicated.

• Radiation Oncology Journal
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• v.23 no.1
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• pp.51-60
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• 2005

Purpose : Selective inhibition of multiple molecular targets may improve the antitumor activity of radiation. Two specific inhibitors of selective cyclooxygenase-2 (COX-2) and epidermal growth factor receptor (EGFR) were combined with radiation on the HeLa cell line. To investigate cooperative mechanism with selective COX-2 inhibitor and EGFR blocker, in vitro experiments were done. Materials and Methods : Antitumor effect was obtained by growth inhibition and apoptosis analysis by annexin V-Flous method. Radiation modulation effects were determined by the clonogenic cell survival assay. Surviving fractions at 2 Gy ($SF_2$) and dose enhancement ratio at a surviving fraction of 0.25 were evaluated. To investigate the mechanism of the modulation of radiosensitivity, the cell cycle analyses were done by flow cytometry. The bcl-2 and bax expressions were analyzed by western blot. Results : A cooperative effect were observed on the apoptosis of the HeLa ceil line when combination of the two drugs, AG 1478 and NS 398 with radiation at the lowest doses, apoptosis of $22.70\%$ compare with combination of the one drug with radiation, apoptosis of $8.49\%$. In cell cycle analysis, accumulation of cell on $G_0/G_l$ phase and decrement of S phase fraction was observed from 24 hours to 72 hours after treatment with radiation, AG 1478 and NS 398. The combination of NS 398 and AG 1478 enhanced radiosensitivity on a concentration-dependent manner in HeLa cells with dose enhancement ratios of 3.00 and $SF_2$ of 0.12 but the combination of one drug with radiation was not enhanced radlosensitivity with dose enhancement ratios of 1.12 and SF2 of 0.68 (p=0.005). The expression levels of bcl-2 and bax were reduced when combined with AG 1478 and NS 398. Conclusion : Our results indicate that the selective COX-2 inhibitor and EGFR blocker combined with radiation have potential additive or cooperative effects on radiation treatment and may act through various mechanisms including direct inhibition of tumor cell proliferation, suppression of tumor cell cycle progression and inhibition of anti-apoptotic proteins.

• Journal of the Korean Society of Food Science and Nutrition
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• v.44 no.7
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• pp.975-982
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• 2015

Piceatannol (trans-3,4,3',5'-trihydroxystilbene), a natural stilbene, is an analogue of resveratrol. In the present study, possible mechanisms by which piceatannol exerts its pro-apoptotic action in cultured human oral cancer YD-15 cells were investigated. To investigate whether or not piceatannol has effects on cancer cell viability, human oral YD-15 cells were treated with piceatannol (0, 50, and $100{\mu}M$). Piceatannol treatment ($100{\mu}M$) showed the strongest inhibition of cell proliferation and reduced cell viability in a dose-dependent manner. Chromatin condensation detected by DAPI staining significantly increased in a concentration-dependent manner, indicating apoptosis. Piceatannol treatment activated initiator Bax (pro-apoptotic) and cPARP in a concentration-dependent manner. Further, piceatannol induced down-regulation of Bcl-2 (anti-apoptotic). We also evaluated the activity of piceatannol against oral cavity cancer tumors in mice. Piceatannol-treated nude mice bearing YD-15 xenograft tumors exhibited significantly reduced tumor volume and weight due to the potent effect of piceatannol on tumor cell apoptosis, as determined by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay. Immunohistochemistry staining showed elevated expression of cleaved-caspase-3 as well as reduced expression of Ki-67 in the piceatannol-treated group. Therefore, piceatannol can be developed as a cancer preventive medicine due to its growth inhibitory effects and induction of apoptosis in human oral cancer cells.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.44 no.3
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• pp.249-258
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• 2018

Airborne pollution causes oxidative damage, inflammation, and premature aging of skin. Resveratrol is a polyphenol compound that has various biological activities such as antioxidant, anti-inflammation, and anti-melanogenic activities but it is unstable to heat and light. Resveratryl triacetate (RTA) is a new cosmetic ingredient that is more stable than resveratrol and its skin safety and whitening efficacy have been reported previously. The purpose of this study was to examine the effects of resveratrol and resveratryl triacetate (RTA) on the inflammatory responses of human epidermal keratinocytes (HEKs) exposed to airborne particulate matters with a diameter of < $10{\mu}m$ (PM10). Cultured HEKs were exposed to PM10 in the absence or presence of resveratrol and RTA. Assays were undertaken to determine cell viability, the production of reactive oxygen species (ROS), and the expression of inflammatory cytokines. PM10 treatment decreased cell viability, and increased the expression of pro-inflammatory cytokines such as tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$), $interleukin-1{\beta}$ ($IL-1{\beta}$), interleukin-6 (IL-6), and interleukin-8 (IL-8). Resveratrol and RTA reduced cell death and ROS production induced by PM10. PM10-induced mRNA expression of the inflammatory cytokines was either attenuated (IL-6), or enhanced ($IL-1{\beta}$), or unaffected ($TNF-{\alpha}$ and IL-8) by resveratrol and RTA. PM10-induced IL-6 protein expression was attenuated by resveratrol and RTA. This study suggests that resveratrol and RTA have activities regulating cell damage and inflammatory responses of the skin exposed to airborne particulate matters.

• Journal of the Korean Society of Food Science and Nutrition
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• v.41 no.12
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• pp.1663-1670
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• 2012

The inhibitory effects of rose hip (Rosa canina L.) water extracts from two different manufactures on osteoarthritis was comparatively investigated in primary cultures of rat cartilage cells. To identify the effects of rose hip extracts against $H_2O_2$ (300 ${\mu}M$, 2 hr) treatment, cell survival was measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell survival increased by rose hip extracts in the range of 100 to 600 ${\mu}g/mL$ of $H_2O_2$ treatment. To determine the anti-inflammatory effects of rose hip extracts, tumor necrosis factor alpha (TNF-${\alpha}$), nitric oxide (NO), and Cox-2 expression were measured after lipopolysaccharide (LPS) activation. TNF-${\alpha}$ level with rose hip extract treatment was decreased by 27.4% and 31.9% at 600 ${\mu}g/mL$ of $H_2O_2$ treatment. Nitric oxide was inhibited by rose hip extract at 100~600 ${\mu}g/mL$ of $H_2O_2$ treatment in a dose-dependent manner. In addition, Cox-2 protein expression was dose-dependently decreased while Cox-1 had no change in expression level. The severity of osteoarthritis is controlled by a balance between anabolic and catobolic factors in an articulation, therefore the expression of these factors plays a critical role in preventing osteoarthritis. In measuring anabolic factors, the genetic expression of collagen type I increased with rose hip treatment, while the genetic expression of collagen II did not change. In addition, the genetic expression of aggrecan (proteoglycan core protein) was significantly increased. while the genetic expression of matrix metalloproteinase (MMP) 3, 7 and 13, known catabolic factors, was significantly inhibited by treatment with rose hip extract. The expression of MMP13 was especially highly influenced. In conclusion, rose hip water extracts show inhibitory effects on cell death by $H_2O_2$ mediated oxidative stress, which is related to inhibitory effects on inflammation due to TNF-${\alpha}$, NO, and Cox-2. The ability of rose hip extracts to ameliorate inflammation in primary cultures of cartilage cells seems to associate with an increased genetic expression of specific anabolic factors, collagen type I and aggrecan, and a decreased expression of catabolic factors, MMPs (3, 7, and 13). However, there were no significant differences between rose hip extracts from the two manufacturers.

• Journal of the Korean Society of Food Science and Nutrition
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• v.38 no.1
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• pp.25-31
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• 2009

This study was carried out to investigate the mutagenic, antimutagenic, cytotoxicity and antitumor effects of Adenophora triphylla (AT). AT was extracted with 70% ethanol and then further fractionated to hexane, chloroform, ethyl acetate, butanol and water. Antimutagenic, cytotoxicity and antitumor effects of AT extracts were measured by using Ames test, SRB method, and the tumor growth inhibition test. AT extracts did not show any mutagenicity in the Ames test; however, 70% ethanol extracts and its fractions had strong antimutagenic effects against mutation induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and 4-nitroquinoline-1-oxide (4NQO). The ethyl acetate fraction of AT (200 ${\mu}g$/plate) showed approximately 66.5% inhibitory effect on the mutagenesis induced by 4NQO against TA98 strain, whereas 83.3% and 75.1% inhibitions were observed on the mutagenesis induced by MNNG and 4NQO against TA100 strain. In anticancer effects, the cytotoxicity of AT extract and its fractions against cancer cell lines including human cervical adenocarcinoma (HeLa), human hepatocellular carcinoma (Hep3B), human breast adenocarcinoma (MCF-7), human gastric carcinoma (AGS), human lung carcinoma (A549) and transformed primary human embryo kidney (293) were investigated. The treatment of 1 mg/mL AT ethyl acetate faction had the highest cytotoxicity of 79.9%, 74.9%, 66.0%, 71.0% and 74.3% against HeLa, Hep3B, MCF-7, AGS and A549 cells, respectively. In contrast, the extract and its fractions showed only $3{\sim}36%$ cytotoxicity for a normal human kidney cell line (293). In vivo anti-cancer effect of Adenophora triphylla extract was tested using Balb/c mice transplanted sarcoma-180 cells. Adenophora triphylla ethyl acetate fraction showed the highest inhibition rate of 37.2% at the 50 mg/kg concentration.

• Journal of Life Science
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• v.22 no.7
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• pp.964-969
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• 2012

Genistein, a predominant isoflavone, has been shown to inhibit the growth of various cancer cells in vitro and in vivo without toxicity to normal cells. In the present study, we investigated the effects of genistein on the activity and the expression of matrix metalloproteinases (MMPs) in MCF-7 and MDA-MB-231 human breast adenocarcinoma cells. Our findings showed that MMP-9 and -2 activation was significantly increased in response to 12-O-tetradecanoyl phorbol-13-acetate (TPA). However, the increased activities of MMP-9 and -2 in TPA-treated cells were concentration-dependently inhibited by treatment with genistein, and this was also correlated with a decrease in the expression of their mRNA and proteins. In addition, a matrigel invasion assay showed that genistein reduced TPA-induced invasion of MCF-7 and MDA-MB-231 cells. Although further in vivo studies are needed, these results suggest that genistein treatment may inhibit tumor cell invasion and, therefore, act as a dietary source to decrease the risk of cancer metastasis.

• Korean Journal of Clinical Laboratory Science
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• v.49 no.2
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• pp.69-78
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• 2017

Cordyceps militaris has been used in traditional Chinese medicine owing to its anticancer and immunomodulatory activities. Germanium compounds have also been shown to be associated with many pharmacological functions, such as antimicrobial, antiviral, antitumor, antimutagenic, and immunomodulating effects. In this study, we examined the biological properties of hot water extract from mycelial liquid culture of germanium-enriched C. militaris (CMGe). CMGe displayed a concentration-dependent antiproliferation activity against four human cancer cell lines. The antiproliferative activity of CMGe was 2-4-fold lower than that of hot water extract from mycelial liquid culture in C. militaris (CM). However, CM had a concentration-dependent cytotoxicity to human bone marrow-derived mesenchymal stem cells (MSCs). Contrastingly, CMGe did not cause any cellular damage to MSCs. MSCs cultured with CMGe displayed an increased proliferative activity with no cytotoxic effect. The oral administration of CMGe inhibited increased tumor volume and weight compared with the control group. CMGe has the potential to be used as an industrial product in medicinal foods as well as in pharmaceutical products.

• Food Science of Animal Resources
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• v.38 no.4
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• pp.780-793
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• 2018

This study was conducted to compare the anti-allergic effects of a whey protein concentrate (WPC) and WPC hydrolysate. WPC hydrolysate was prepared using enzymatic digestion for 8 h with trypsin and ${\alpha}$-chymotrypsin, after which it was freeze-dried. The allergic parameters assessed in rat basophilic leukemia (RBL)-2H3 cells were degranulation and release of ${\beta}$-hexosaminidase, release of tumor necrosis factor $(TNF)-{\alpha}$, and changes in the expression of $IL-1{\beta}$, IL-4, and IL-10 by real time polymerase chain reaction (PCR). During preparation of the WPC hydrolysate, hydrolysis increased rapidly from 0 to 10 min and then gradually increased slowly from 1 h onwards, achieving a final degree of hydrolysis of 78.50%. The SDS-PAGE analysis revealed a reduction in the intensity of several protein bands in the WPC hydrolysate compared to the WPC. IgE-induced ${\beta}$-hexosaminidase release from RBL-2H3 cells was decreased to a higher degree following treatment with the hydrolysate compared to WPC treatment. W500 ($500{\mu}g/mL$ WPC) showed the least inhibition of ${\beta}$-hexosaminidase release, but there was no significant difference between W500 and W1000 ($1,000{\mu}g/mL$) (p<0.05). H1000 ($1,000{\mu}g/mL$ WPC hydrolysate) inhibited ${\beta}$-hexosaminidase release by 39%. Compared to the control, treatment with H1000 decreased $TNF-{\alpha}$ secretion to 11.87 pg/mL. The gene expression levels of IL-1${\beta}$, IL-4, and IL-13 were all significantly decreased in hydrolysate (p<0.05). In the case of $IL-1{\beta}$ and IL-4, the expression levels in W1000 treated cells were decreased by 73.67% and 65%, respectively, and that of IL-13 was decreased by 66.43% compared to the control.