• Korean Journal of Pharmacognosy
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• v.23 no.2
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• pp.89-95
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• 1992

The water extract of Gamidaebo-Tang depressed the lethal toxicity of cis-platin$(45{\mu}M/kg,\;s.c.)$, and mitomycin C (6mg/kg, s.c.). Significant depression of renal toxicity(indicated by an increased blood urea nitrogen value and creatinine value) of cis-platin $(35{\mu}M/kg)\;s.c.)$, was observed in mice treated with Gamidaebo-Tang. In rats treated with mitomycin C and Gamidaebo-Tang, the increased LDH activity and reduced total protein and albumin contents by mitomycin C were significantly depressed. The number of WBC was significantly increased in rats treated with mitomycin C but in the rats treated with mitomycin C and Gamidaebo-Tang, the number of WBC was increased and the hematocrit value and the number of RBC and Hgb were significantly increased in the dose-dependent manner. Therefore, bone marrow toxicity of mitomycin C in the rats treated with Gamidaebo-Tang was depressed. In the end, alleviative effects of the side actions of cis-platin and mitomycin C were acknowledged by combined usage of Gamidaebo-Tang and these anti-neoplastic drugs.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.1
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• pp.199-203
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• 2014

Background: Rosuvastatine, doxazosin, repaglinide and oxcarbazepin are therapeutic drugs available in the market for the treatment of different diseases. Potential to display antitumor activities has also been suggested. The aim of the current study was to evaluate their in vitro effects on some human transformed cell lines. Materials and Methods: Cytotoxicity of the four drugs was tested in MCF-7, HeLa and HepG2 cells by the neutral red assay method and also the effect of rosuvastatine and doxazosin against Ehrlich Ascities Carcinoma Cells (EACC) by trypan blue assay. Results: Rosuvastatine exerted the greatest cytotoxic effect against HepG2 cells with an $IC_{50}$ value of $58.7{\pm}69.3$; in contrast doxazosin showed least activity with $IC_{50}=104.4{\pm}115.7$. Repaglinide inhibited the growth of both HepG2 and HeLa cells with $IC_{50}$ values of $87.6{\pm}117.5$ and $89.3{\pm}119.5$, respectively. Oxcarbazepine showed a potent cytotoxicity against both HeLa ($IC_{50}=19.4{\pm}43.9$) and MCF7 cancer cells (($IC_{50}=22{\pm}35.7$).On the other hand the growth of EACC was completely inhibited by doxazosine (100% inhibition) while rosuvastatine had weak inhibitory activity (11.6%). Conclusions: The four tested drugs may have cytotoxic effects against hepatic, breast and cervical carcinoma cells; also doxazosine may inhibit the growth of endometrial cancer cells. Further investigations in animals are needed to confirm these results.

• Microbiology and Biotechnology Letters
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• v.24 no.1
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• pp.37-43
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• 1996

Augmentation of antitumor activity of antitumor drugs in combination with Lactobacillus casei HY2782 (LC2782) was studied against Sarcoma-180 (S-180) and Lewis lung carcinoma (3LL). Antitumor drugs used in this study were 5-fluorouracil (5-fu) and cyclophosphamide (CP). The prolongation effect of LC2872 on the life span of mouse intraperitoneally implanted with S-180 was stronger than that of OK-432 and BCG, while the inhibitory effect of OK-432 and BCG on the growth of 3LL solid tumor was a little stronger than that of LC2782. Average survival rates of mice administrated LC2782, OK-432 and BCG were 192%, 141%, and 112%, respectively, when that of the control was 100%, Intralesional administration of 5-Fu, CP, 5-Fu+LC2782 and CP+LC2782 resulted in 93%, 69%, 99% and 73% inhibition rates against 3LL solid tumor proliferation. The combination therapy of 5-Fu or CP with LC2782 significantly prolonged the life span of S-180-inoculated ICR mice. Average survival rates of mice administrated 5-Fu and CP alone were 115% and 99%. Furthermore, survival rates of mice administrated 5-Fu and CP in combination with LC2782 were 226% and 244%, respectively.

• Natural Product Sciences
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• v.19 no.1
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• pp.54-60
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• 2013

Rhus verniciflua Stokes (Anacadiaceae) is a plant that is native to East Asian countries, such as Korea, China, and Japan, and it has been found to exert various biological activities including antioxidative, anti-aggregatory, anti-inflammatory, anti-mutagenic, and apoptotic effects. Sulfuretin is one of the major flavonoid component isolated from the heartwood of R. verniciflua. Reactive oxygen species (ROS), produced via dental adhesive bleaching agents and pulpal disease, can cause oxidative stress. In the present study, we isolated sulfuretin from R. verniciflua and demonstrated that sulfuretin possesses cytoprotective effects against hydrogen peroxide ($H_2O_2$)-induced dental cell death. $H_2O_2$ is a representative ROS and causes cell death through necrosis in human dental pulp (HDP) cells. $H_2O_2$-induced cytotoxicity and production of ROS were blocked in the presence of sulfuretin, and these effects were dose dependent. Sulfuretin also increased heme oxygenase-1 (HO-1) protein expression. In addition, to determine whether sulfuretin-induced HO-1 expression mediated this cytoprotective effect, HDP cells were cotreated with sulfuretin in the absence or presence of SnPP, an inhibitor of HO activity. Sulfuretin-dependent HO-1 expression was required for suppression of $H_2O_2$-induced HDP cell death and ROS generation. These results indicate that sulfuretin-dependent HO-1 expression was required for the inhibition of $H_2O_2$-induced cell death and ROS generation. In addition, sulfuretin may be used to prevent functional dental cell death and thus may be useful as a pulpal disease agent.

• Nutrition Research and Practice
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• v.5 no.5
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• pp.381-388
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• 2011

We compared the effects of genistein and daidzein on the expression of chemokines, cell adhesion molecules (CAMs), and endothelial nitric oxide synthase (eNOS) in tumor necrosis factor (TNF)-${\alpha}$-stimulated human umbilical vascular endothelial cells (HUVECs). TNF-${\alpha}$ exposure significantly increased expression of monocyte chemoattractant protein (MCP)-l, vascular adhesion molecule (VCAM)-1, and intercellular adhesion molecule-1. Genistein significantly decreased MCP-l and VCAM-l production in a dose-dependent manner, whereas CAM expression was not significantly lowered by genistein treatment. However, daidzein slightly decreased MCP-l production. The effects of genistein and daidzein on MCP-l secretion coincided with mRNA expression. Pre-treatment with either genistein or daidzein elevated eNOS expression and nitric oxide production disturbed by TNF-${\alpha}$ exposure. A low concentration of isoflavones significantly inhibited nuclear factor (NF)${\kappa}$B activation, whereas a high dose slightly ameliorated these inhibitive effects. These results suggest that genistein had a stronger effect on MCP-l and eNOS expression than that of daidzein. Additionally, NF${\kappa}$B transactivation might be partially related to the down-regulation of these mRNAs in TNF-${\alpha}$-stimulated HUVECs.

• Journal of Chest Surgery
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• v.22 no.6
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• pp.914-920
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• 1989

Bleomycin and cyclophosphamide are widely used and effective anti-cancer agents for treatment of various forms of cancer. Bleomycin has no myelotoxicity, but because of potential risk of pulmonary complications including interstitial pneumonitis and idiopathic interstitial pulmonary fibrosis, it has been limited in use. Some investigator has also suggested that cyclophosphamide can induce pulmonary toxicity like bleomycin. Recently, The combination chemotherapy including bleomycin and cyclophosphamide has been adopted effectively in some types of cancer. But there are no available literatures for synergistic effect of pulmonary toxicity in combination chemotherapy including these two drugs. We tried this study to observe synergism of pulmonary toxicity using these two drugs in rats. The animals were divided into five groups: group 1 received intra-peritoneal injection of saline, group 2-a received only bleomycin 0.1 mg [0.4 mg/kg] by intra-peritoneal injection twice a week, group 2-b received only bleomycin 0.5 mg [2 mg/kg] by intra-peritoneal injection twice a week, group 3-a received bleomycin 0.1 mg [0.4 mg/kg] twice a week +cyclophosphamide 5 mg [20 mg/kg] two weeks interval by intra-peritoneal injection, group 3-b received bleomycin 0.5 mg [2 mg/kg] twice a week + cyclophosphamide 5 mg[20 mg/kg] two weeks interval by intra-peritoneal injection. The animals were sacrificed at 2 and 4 weeks later. Lung tissues were obtained and observed by light microscope. The results are as follows: 1. The pathologic findings of group 1 were normal without change. 2. There was no difference between group 2-a and group 3-a at 2 weeks later, group 3-a, however, revealed more severe change in lung tissue at 4 weeks later compared with group 2-a. 3. In group 3-b there was more severe pulmonary injury compared with group 2-b at 2 and 4 weeks later. We conclude that the combined administration of bleomycin and cyclophosphamide induce more severe pulmonary toxic effect than bleomycin administration alone and the combination chemotherapy including these two drugs will be require special attention to selection of the dose of each drug.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.6
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• pp.3429-3436
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• 2013

Cervical cancer is a major health problem worldwide and is the most frequent cause of cancer in women in India. Early detection and affordable drugs with clinical efficacy have to go hand-in-hand in order to comprehensibly address this serious health challenge. Plant-based drugs with potent anticancer effects should add to the efforts to find a cheap drug with limited clinical side effects. Keeping this very purpose in mind, an attempt has been made in this review to explore the potential of plant extracts or constituents known to exhibit antitumorigenic activity or exert cytotoxic effect in human cervical carcinoma cells. Alkaloids such as those isolated from C. vincetoxicum and T. Tanakae, naucleaorals A and B, isolated from the roots of N. orientalis, (6aR)-normecambroline, isolated from the bark of N. dealbata appear promising in different human cervical carcinoma cells with the $IC_{50}$ of 4.0-8 ${\mu}g/mL$. However, other compounds such as rhinacanthone and neolignans isolated from different plants are not far behind and kill cervical cancer cells at a very low concentrations. Among plant extracts or its constituents that enhance the effect of known anticancer drugs, noni, derived from the plant M. citrifolia perhaps is the best candidate. The cytotoxic potency and apoptotic index of cisplatin was found to significantly enhanced in combination with noni in different human cervical carcinoma cells and it therefore holds significance as promising herbal-based anticancer agent. However, efficacy needs to be further investigated in various cervical cell lines and more importantly, in in vivo cervical cancer models for possible use as an alternative and safe anticancer drug.

• Archives of Pharmacal Research
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• v.24 no.2
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• pp.150-158
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• 2001

The activity of nonsteroidal antiinflammatory drugs (NSAIDs) in rheumatoid arthritis is not only due to the inhibition of the production of prostaglandins, which can even have beneficial immunosuppressive effects in chronic inflammatory processes. Since we speculated that these drugs could also act by protecting endogenous proteins against denaturation, we evaluated their effect on heat-induced denaturation human serum albumin (HSA) in comparison with several fatty acids which are known to be potent stabilizers of this protein. By the Mizushimas assay and a recently developed HPLC assays we observed that NSAIDs were slightly less active [$EC_{50}~10^{-5}-10^{-4}$ M] than FA and that the HPLC method was less sensitive but more selective than the turbidimetric assay, i.e. it was capable of distinguishing true antiaggregant agents like FA and NSAIDs from substances capable of inhibiting the precipitation of denatured protein aggregates. In conclusion, this survey could be useful for the development of more effective agents in protein condensation diseases like rheumatic disorders, cataract and Alzheimers disease.

• The Korean Journal of Physiology and Pharmacology
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• v.9 no.3
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• pp.149-153
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• 2005

The aim of the present study was to determine whether serotonergic drugs could reverse lipopolysaccharide (LPS)-induced anorexia in rats. LPS ($500{\mu}g$/kg body weight) and all serotonergic drugs, except for 8-OH-DPAT (subcutaneous), were injected intraperitoneally into Sprague-Dawley rats. Without the LPS injection, 8-OH-DPAT (1A agonist), metergoline (1/2 antagonist), and mianserin (2A/2C antagonist) exerted no effects on food intake at any of the doses tested, but ketanserin (2A antagonist) caused an increase of food intake at 4 mg/kg. RS-102221 (2C antagonist) reduced food intake at 2 and 4 mg/kg. LPS reduced food intake 1 hour after injection, and food intake remained low until the end of measurement period (24 hours) (p<0.05). Pretreatment of rats with 8-OH-DPAT partially recovered of cumulative food intake at all measured times (2, 4, 6, 8, and 24 hours after LPS injection). Pretreatment with metergoline resulted in a partial recovery of cumulative food intake at 2, 4, 6, and 8 hours, but not at 24 hours. Ketanserin caused partial recovery at 2 and 4 hours only. Mianserin and RS-102221 had no effects on LPS-reduced food intake. A variety of serotonergic drugs ameliorated anorexic symptoms, which suggesting that the serotonin system plays a role in LPS-induced anorexia.

• Nutrition Research and Practice
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• v.7 no.6
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• pp.446-452
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• 2013

Chronic consumption of a high-fat, high-sucrose (HFHS) diet increases insulin resistance and results in type 2 diabetes mellitus in C57BL/6J mice. Hyperglycemia in diabetics increases oxidative stress, which is associated with a high risk of diabetic complications. The purpose of this study was to examine the hypoglycemic and antioxidant effects of chamnamul [Pimpinella brachycarpa (Kom.) Nakai] in an animal model of type 2 diabetes. The ${\alpha}$-glucosidase inhibitory activity of a 70% ethanol extract of chamnamul was measured in vitro. Five-week-old male C57BL/6J mice were fed a basal or HFHS diet with or without a 70% ethanol extract of chamnamul at a 0.5% level of the diet for 12 weeks after 1 week of adaptation. After sacrifice, serum glucose, insulin, adiponectin, and lipid profiles, and lipid peroxidation of the liver were determined. Homeostasis model assessment for insulin resistance (HOMA-IR) was determined. Chamnamul extract inhibited ${\alpha}$-glucosidase by 26.7%, which was 78.3% the strength of inhibition by acarbose at a concentration of 0.5 mg/mL. Serum glucose, insulin, and cholesterol levels, as well as HOMA-IR values, were significantly lower in the chamnamul group than in the HFHS group. Chamnamul extract significantly decreased the level of thiobarbituric acid reactive substances and increased the activities of superoxide dismutase, catalase, and glutathione peroxidase in the liver compared with the HFHS group. These findings suggest that chamnamul may be useful in prevention of hyperglycemia and reduction of oxidative stress in mice fed a HFHS diet.