• 동의생리병리학회지
• /
• 제30권3호
• /
• pp.164-176
• /
• 2016

This study was perfomed to investigate the effects of Chunghyul-plus(CHP) on oxidative damage and hyperlipidemia in db/db mouse. After treatment with CHP, safety in cytotoxicity, heavy metal toxicity, production of reactive oxygen species(ROS), nitric oxide (N0) and proinflammatory cytokine IL-Ib, TNF-a, IL-6 in RAW 264.7 cells. Serum total cholesterol, LDL cholesterol, HDL cholesterol, triglyceride, insulin, GLP-1, glucose, food intake, body weight, organ weight, AST, ALT, ALP, BUN, creatine and histologic change of liver and aorta were measured in db/db mouse after oral administration of CHP. CHP showed safety in cytotoxicity and toxicity of liver and kidney for logn time administration. CHP increased the DPPH and ABTS radical scavenging activity. CHP showed significant inhibitory effect on reactive oxygen species (ROS), and showed inhibitory effect on nitiric oxide(NO) compared to control group. CHP decreased cytokine IL-6 production significantly, and decreased IL-1β and TNF-α compared to control group. CHP decreased body and organ weitht, intake food, and glucose levels compared to control group. CHP decreased total cholesterol and triglyceride significantly, and decreased LDL-cholesterol levels and increased HDL-cholesterol levels compared to control group. CHP decreased atherogenic index and cardiac risk factor significantly. CHP increased serum insulin and GLP-1 compared to control group. In histologic examination, lipophagy in the liver and aorta decreased in CHP treated mice and the cell was regular and boundary of vessel wall was clear compared to control group. These results suggest that CHP is effective in antioxidation activity and treatment and prevention of hyperlipidemia, atherosclerosis, diabetes, ischemic heart disease, stroke and other cardiocerebrovascular disease.

• Biomolecules & Therapeutics
• /
• 제5권2호
• /
• pp.125-132
• /
• 1997

Cisplatin, a platinum-complex, is currently one of the most effective compounds used in the treat-ment of solid tumors. However, its use is limited by severe side effects such as renal toxicity. Our platinum-based drug discovery program is aimed at developing drugs capable of diminishing toxicity and improving selective cytotoxicity. We synthesized new Pt (II) complex analogue containing 1,2-diaminocyclohexane (DACH) as carrier ligand and 1,2-bis (diphenylphosphino) ethane (DPPE) as a leaving group. Furthermore, nitrate was added to improve the solubility. A new series of [Pt(cia-DACH)(DPPE)] . $2NO_3$ (PC) was synthes-ized and characterized by their elemental analysis and by various spectroscopic techniques [infrared (IR), $_{13}$carbon nuclear magnetic resonance (NMR)] .PC demonstrated acceptable and significant antitumor activity against SKOV-3 and OVCAR-3 human ovarian carcinoma cell lines as compared with that of cisplatin. The cytotoxicity of PC in normal cells was found quite less than that of cisplatin using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), ($^3$H)thymidine uptake and glucose consumption tests in rabbit renal proximal tubular cells, human renal cortical cells and tissues. In conclusion, PC is considered to be more selective cytotoxicity toward human ovarian cancer cells than normal human/rabbit kidney cells.

• Asian Pacific Journal of Cancer Prevention
• /
• 제13권8호
• /
• pp.3589-3593
• /
• 2012

Objective: Evaluation and assessment of response rate, duration and toxicity in patients subjected to 5-FU based chemotherapy. Background: The therapeutic ratio shifts with different 5FU/LV regimens and none yet serve as the internationally accepted Gold Standard. A bimonthly regimen of high dose leucovorin is reported to be less toxic and more effective than monthly low dose regimens. We here compare therapeutic responses and survival benefit of the two regimens in poor prognosis patients with advanced colorectal carcinoma. Patients and Methods: A total of 35 patients with histologically confirmed colorectal carcinoma were subjected to de Gramont and Mayo Clinic regimen. Nineteen patients were treated with high dose folinic acid ($200mg/m^2$), glucose 5%, 5-FU ($400mg/m^2$) and 22 hr. CIV ($600mg/m^2$) for two consecutive days every two weeks. These patients had failed responses to previous chemotherapy and were above sixty years of age with poor general status. Sixteen patients (six below 60 years) with progressive disease were subjected to low dose folinic acid ($20mg/m^2$)for five days, 5FU($425mg/m^2$) injection bolus for 5 days, every five weeks. An initial evaluation was made in sixty days and responders were reevaluated at sixty days interval or earlier in case of clinical impairment. Based on positive prognosis, the therapy was continued. Evaluation of treatment response was made on the basis of WHO criteria. Results: The response rate was 44% in thirty four evaluable patients, with 4 complete responses (11.8%) and 11 (32.4%) partial responses. The two schedules were well tolerated, whereas, mild toxicity without WHO Grade ${\geq}2$ events was assessed. The response duration was extended (12 months) in a few patients with age above sixty years treated by high dose bimonthly regimen of 5FU/LV. Conclusion: The regimens are safe and effective in advanced colorectal carcinoma patients with poor general status.

• Journal of Microbiology and Biotechnology
• /
• 제14권2호
• /
• pp.243-249
• /
• 2004

The toxicity of inorganic sulfuric acid as a stressor was characterized in Saccharomyces cerevisiae KNU5377. In this work, we examined physiological responses to low extracellular pH $(pH_{ex})$ caused by inorganic $H_2SO_4$, which could not affect cell growth after pH was adjusted to an optimum with Trizma base. The major toxicity of sulfuric and was found to be reduction of environmental pH, resulting in stimulation of plasma membrane ${H^+}-ATPase$, which in turn contributed to intracellular alkalinization. Using a pH-dependent fluorescence probe, 5-(and-6)-carboxy SNARF-1, acetoxymethyl ester, acetate (carboxy SNARF-1 AM acetate), to determine $pH_{in}$, we found that color was dependent on the changes of intracellular pH which coincided with calculated $pH_{in}$ of alkalinization up to approximately pH 7.3. This alkalinization did not seem to affect survival of these cells exposed to 30 mM sulfuric acid, which lowered the $pH_{ex}$ of the glucose containing growth media up to approximately pH 3.0; however, the cells could grow only up to 70% of the maximum growth in the same media, when 30 mM sulfuric acid was added.

• 대한한방내과학회지
• /
• 제30권3호
• /
• pp.481-494
• /
• 2009

Background : Radix Sophora Flavescentis (SF) is used for the treatment of diabetes mellitus in Traditional Korean Medicine. However, little is known about the effects of Radix Sophora Flavescentis extract (SFE) on the hypoglycemic mechanism. Objective : We performed a series of experiments to verify the effects of SFE on the proliferation of RIN-m5F, the secretion and synthetic processes of insulin with glucose stimulation and inhibition of $\alpha$-glucosidase. Methods : Various amounts of SFE were added to the RIN-m5F cell culture to identify the effects on the cell proliferation, total amounts of insulin secretion, and related gene expression at the molecular level. Also to identify the inhibitory effect on the $\alpha$-glucosidase activities, ${\rho}NPG$ assay was done with various SFE concentrations followed by comparison with control. Results : SFE did not show considerable effects on RIN-m5F cells proliferation, insulin secretion or insulin mRNA expression, whichever phenomena did not depend on the glucose concentration. However, SFE significantly inhibited $\alpha$-glucosidase activity in a dose dependent manner compared to control. Conclusions : This study showed that SFE has potent $\alpha$-glucosidase inhibitory activity. Thus, SF may by used for the improvement of overall glycemic control. Further mechanism studies on the lipid toxicity and oxidation stress of SF seem to be necessary.

• 대한한방내과학회지
• /
• 제30권2호
• /
• pp.338-354
• /
• 2009

Objective : Gamijihwang-tang(GJT) has been used as a therapeutic agent for hyperlipidemia in oriental medicine for several years. This study was performed to investigate the effects of GJT on hyperlipidemia in rats using diverse biological methods. Method : Hyperlipidemia was induced by a hyper-lipidemic diet fed for 4 weeks. Total cholesterol, LDL-cholesterol, HDL-cholesterol, triglyceride, and glucose were measured in the serum after an oral administration of GJT. Lipid peroxidase, SOD, catalase, ACAT, and HMG-CoA were measured in liver after oral administration of GJT. Result: 1. GJT showed safety against cytotoxicity and toxicity in liver. 2. GJT significantly decreased rat's body and liver weight. 3. GJT significantly decreased serum total cholesterol and LDL-cholesterol, but increased serum HDL-cholesterol. 4. GJT significantly decreased serum triglyceride and glucose. 5. GJT significantly decreased lipid peroxidation and increased SOD and catalase in liver. 6. GJT significantly decreased ACAT and HMG-CoA reductase of cholesterol manifestation in liver. Conclusions : These results suggest that GJT might be effective in treatment and prevention of hyperlipidemia.

• 대한의생명과학회지
• /
• 제9권4호
• /
• pp.195-201
• /
• 2003

Aromatic hydrocarbons are of major concern among genotoxic chemicals due to their toxicity and persistence. Some microorganisms can utilize aromatic hydrocarbons as carbon and energy sources by inducing expression of catabolic operon(s). The XylR regulatory protein activates transcription of the catabolic enzymes to degrade BTEX (benzene, toluene, ethylbenzene, and xylene) from its cognate promoters, Pu and Ps upon exposure of the cells to the aromatic hydrocarbons. The activity of XylR on the promoters was previously monitored using luciferase luc reporter system. The xylR, its promoter Pr and the promoter Po for the phenolic compound catabolic operon were introduced upstream of firefly luciferase luc in the pGL3b vector to generate about 7.1 kb of pXRBTEX. Here E. coli harboring the plasmid was freeze-dried under various conditions to fin,d optimal conditions for storage and transport. The cell viability and luciferase activity were maintained better, when the cells were freeze-dried at -7$0^{\circ}C$ in the addition of the 10% skim milk or 12% sucrose. However, coaddition of protectants such as 10% skim milk plus 10% glucose or 12% sucrose plus 10% glucose, resulted in much better viability and bioluminescence activity compared with the effect of single addition of each protectant. In addition, it was shown that the freeze-dried cells maintained almost intact bioluminescent activities and cell viability for at least 1 week after freeze-drying. This work demonstrated that the properly freeze-dried recombinant bacterial cells could be utilized as a whole-cell biosensor for simple and rapid monitoring of BTEX in the environment.

• 한국응용약물학회:학술대회논문집
• /
• 한국응용약물학회 1997년도 춘계학술대회
• /
• pp.74-74
• /
• 1997

Chicory is used popularly. We use leaves of the plant as ordinary mea1, and roots as a substitute of tea materials. It also has been asserted that it has clinical effects on weakness, hepatic disease, diabetes, etc. However, experimental evidences are so insufficient that we started these studies. For antiinflammatory activity, MeOH Ex. was orally administered to rats, and decreased amounts of paw edema induced by carrageenan injection were measured. For bile secretion increament, rats were administered total MeOH, EtOAc fraction, and BuOH fraction Ex. respectively. One hour later, bile ducts were cannulated, and we collected bile every 20 minutes for 4 hours. For hepatoprotective activity, CCl$_4$-intoxicated mouse were treated with MeOH Ex., then s-GPT, S-GOT, and liver weight were measured. For antidiabetic activity, rats were induced diabetes by streptozocin 45mg/kg(i.v) injection. One week later, 1000mg/kg of total MeOH Ex. of chicory root was orally administered. We divided rats into three groups. Group 1 rats were administered only once, group 2 ones once a day for one week, and group 3 ones for three weeks. The concentrations of serum glucose were measured before and after administration. For antihypertensive activity, SHR were administrated total MeOH Ex. of chicory once a day for 8 days, and were measured blood pressure on 1st, 3rd, 6th and 8th day. Total MeOH, EtOAc fraction, and BuOH fraction Ex. increased bile secretion in rats, and decreased liver toxicity induced by CCl$_4$ in mouse. Total MeOH, Ex. of chicory roots has antiinflammatory effect, and decreased blood glucose concentration in group 2 and 3 rats. It was revealed not lowering blood pressure significantly in SHR.

• Journal of Nutrition and Health
• /
• 제30권3호
• /
• pp.252-265
• /
• 1997

This study was performed to investigate effect of dietary fibers in rice and barley on glucose, lipid and cadmium (Cd) metabolism in the rat. Fifty-six male Spague-Dawley rats weighing 244.6$\pm$2.7g were blocked into eight groups according to body weight and raised for four weeks with diets containing 0 or 0.04%(w/w) CdCl2 and four different carbohydrate sources, starch, rice flour, barley flour and mixture of rice and barley flour(7 : 3, w/w). Total dietary fibers and $\beta$-glucan contents of barley were about three times higher than those of rice (10.75% vs. 3.94%, 3.11% vs. 1.06%, respectively). Food intake, weight gain, food efficiency ratio, liver and kidney weights were lower in Cd exposed groups, and barley group among Cd exposed animals showed highest weight gain, food efficiency ratio and organ weights. Fasting serum glucose levels were not significantly different among groups, Serum cholesterol level was lowest in Cd exposed barley group. Serum HDL-cholesterol level was higher in none-Cd exposed starch and barley groups, and HDL-cholesterol : total cholesterol ratios were higher in none-Cd rice and mixed flour groups than other groups. Liver total lipid and triglyceride levels were lowest in barley groups regardless of Cd administration. Fecal total lipid, cholesterol and triglyceride excretions were high in barley and mixed flour groups. Liver Cd concentrations were low in Cd exposed barley and mixed flour groups. In Cd exposed barley group, fecal weight and Cd excretion were highest and Cd retention ratio was lowest among groups. Small intestine metallothionein(MT) concentration was highest in Cd exposed rice group, and kidney MT concentration was highest in Cd exposed barley group. In conclusion, cereals showed different effects on lipid and Cd metabolism that might be mediated by dietary fibers in cereals. Especially $\beta$-glucan-rich barley group showed greatest lipid and Cd lowering effects by increasing fecal lipids and Cd excretions.

• Journal of the Korean Wood Science and Technology
• /
• 제37권3호
• /
• pp.239-244
• /
• 2009

본 연구에서는 느티나무 심재부에서 단리한 7-hydroxy-3-methoxycadalene이 나타내는 세포독성을 경감시키고 물에 대한 낮은 용해도를 향상시킬 목적으로 반응물의 7번 위치에 존재하는 수산기를 친수성이 강하고 세포 독성이 없는 글루코오스로 치환시켜 7-O-${\beta}$-D-glucopyranosyl -3-methoxycadalene을 합성하였으며, 수율은 약 55%에 이르렀다. 7-O-${\beta}$-D-glucopyranosyl -3-methoxycadalene은 반응 전 7-hydroxy-3-methoxycadalene에 비해 물에 대한 수용성이 크게 증가하였다. 카달렌-글루코오스 유도체는 정상 폐조직 세포(WI-38 cell line)와 폐암 세포주(A-549 cell line)에 대한 세포생존율, 즉 반수치사율(IC50)이 각각 $298.2{\mu}m$과 $88.6{\mu}m$로 나타났다. 이러한 결과는 7-hydroxy-3-methoxycadalene에 글루코오스 한 분자를 치환함으로써 폐암세포의 증식억제에 미치는 약리적 효과가 3배 이상으로 향상되었음을 의미한다.