• Bulletin of the Korean Chemical Society
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• v.26 no.6
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• pp.952-958
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• 2005

Angiotensin-converting enzyme (ACE) is known to be primarily responsible for hypertension. Threedimensional quantitative structure-activity relationship (3D-QSAR) models have been constructed using the comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) for a series of 28 ACE inhibitors. The availability of ACE crystal structure (1UZF) provided the plausible biological orientation of inhibitors to ACE active site (C-domain). Alignment for CoMFA obtained by docking ligands to 1UZF protein using FlexX program showed better statistical model as compared to superposition of corresponding atoms. The statistical parameters indicate reasonable models for both CoMFA ($q^2$ = 0.530, $r^2$ = 0.998) and CoMSIA ($q^2$ = 0.518, $r^2$ = 0.990). The 3D-QSAR analyses provide valuable information for the design of ACE inhibitors with potent activity towards C-domain of ACE. The group substitutions involving the phenyl ring and carbon chain at the propionyl and sulfonyl moieties of captopril are essential for better activity against ACE.

• Preventive Nutrition and Food Science
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• v.10 no.2
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• pp.134-139
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• 2005

Seven brown algal species (Ecklonia cava, Ishige okamurae, Sargassum fulvellum, Sargassum horneri, Sargassum coreanum, Sargassum thunbergii and Scytosiphon lomentaria) were hydrolyzed using five proteases (Protamex, Kojizyme, Neutrase, Flavourzyme and Alcalase) and screened for angiotensin 1-converting enzyme (ACE) inhibitory activities. Most algal species examined showed good ACE inhibitory activities after the enzymatic hydrolysis. However, E. cava was the most potent ACE inhibitor of the seven species. Flavourzyme digest of E. cava exhibited an $IC_{50}$ of around $0.3\;{\mu}g/mL$ for ACE; captopril has an $IC_{50}$ of $\~0.05\;{\mu}g/mL$. The Flavourzyme digest was separated to three fractions by an ultrafiltration membrane (5, 10, 30 kDa MWCO) system according to the molecular weights. The active components were mainly concentrated in >30 kD fraction which are composed of the highest protein content $(27\%)$ and phenolic content (261 mg/100 mL) compared to the other two smaller molecular weight fractions. Therefore, the active compounds appear to be relatively high molecular weight complex molecules associated with protein (glycoprotein) and polyphenols. Therefore, E. cave is a potential source of antihypertensive compound.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.5
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• pp.1505-1511
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• 2004

Inhibition of angiotensin converting enzyme (ACE) activity is one of the common antihypertensive methods functioned by drugs such as captopril, lisinopril and enalapril to serve as inhibitors of ACE. This study was designed to compare the effects of enalapril, an angiotensin-converting enzyme inhibitor and GLM002, an oriental medicine, on tail systolic pressure, aorta and plasma properties in spontaneously hypertensive rats (SHR) after 4 weeks of treatment. During the treatment, blood pressure was depressed to normal in GLM002 and enalapril groups. The treatments of enalapril and GLM002 were discontinued in 4 weeks. One week after the treatment stop, systolic blood pressure was smoothly increased in both groups; the increment of blood pressure was slightly greater in GLM002-SHR, but the increment of plasma ACE activity was proportionately similar in each group. In the aspects of the triglyceride, HDL and total cholesterol level, those levels were slightly different among each group. We also conducted clinical dosage of GLM002 to the patients who have mild and severe hypertension for approximately 7 weeks. Clinical treatments also showed remarkable efficiencies on blood pressure (systolic blood pressure, diastolic blood pressure), complete blood count (CBC) routine, differ count (NEUTRO, LYM, MONO, EOS and BASO) and R-chemistry. We conclude that GLM002, like already proven enalapril, plays a role as an angiotensin-converting enzyme inhibitor, and can be suggested as a drug candidate for curing hypertension.

• The Journal of Internal Korean Medicine
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• v.30 no.4
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• pp.832-844
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• 2009

Objectives : This study was to observe the nephroprotective effects of the traditional prescription, Taeksa-san(TSS). TSS has generally been used for treating various renal diseases, including renal failure. Methods : Three different dosages of TSS extract were orally administered once a day for 28 days, At the 23rd day after TSS extract treatment, cisplatin was also treated. Then, 5 days after cisplatin treatment, all the rats (6 groups of 8 rats each) were sacrificed. Changes in the body weight, kidney weight, serum BUN and creatinine levels were observed with changes on the kidney MDA and GSH contents. The results were compared with captopril 100mg/kg, of which the effects on cisplatin-induced acute renal failures are already confirmed. Results : Dramatic decrease of body weight, increase of kidney weight, increase of serum BUN and creatinine levels were detected in the cisplatin control as compared with the intact control. In addition, marked increase of kidney MDA contents and decrease of kidney GSH contents were also detected in the cisplatin control as compared with the intact control. This means that cisplatin-induced ARF is induced by oxidative stress and related lipid peroxidation in the present study. However, these ARFs and inhibition of antioxidant effects induced by cisplatin were dose-dependently reduced by treatment with all three different dosages of TSS extracts. Conclusion : This study suggests that TSS extracts show favorable effects on cisplatin-induced rat ARF.

• The Journal of Internal Korean Medicine
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• v.31 no.3
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• pp.620-630
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• 2010

Purpose : The object of this study was to observe the nephroprotective effects of Manjeonmoktong-san(MJMTS), which has traditionally been used as Korean medicine for treating various renal diseases, on cisplatin-induced rat acute renal failure. Methods : At first, three different dosages of MJMTS extract were orally administered once a day for 28 days. On the 23rd day after MJMTS extract treatment, cisplatin was treated. Then, 5 days after cisplatin treatment, all the rats (6 groups of 8 rats each) were checked in the present study. The changes to the body weight, kidney weight, serum BUN and creatinine levels were observed with changes on the kidney MDA and GSH contents. The results were compared with captopril 100mg/kg in which the effects on cisplatin-induced acute renal failures were already confirmed. Results : It showed dramatical decrease on the body weight, increase of serum BUN and creatinine levels were detected in cisplatin control as compared with intact control. In addition marked increase of kidney MDA contests and decrease of kidney GSH contents were also detected in cisplatin control as compared with intact control. it means that cisplatin induced ARF are induced by oxiidative stress and related lipid peroxidation in the present study. However, these ARFs and inhibition of antioxidant effects induced by cisplatin were dose-dependently reduced by treatment of all three different dosages of MJMTS extracts. Conclusion : This study suggests that MJMTS extracts have favorable effects on the cisplatin-induced rat ARF.

• The Korean Journal of Physiology and Pharmacology
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• v.11 no.5
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• pp.189-195
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• 2007

To study the protective effects of antioxidants on the radiation damages of the cells, vascular smooth muscle cells(VSMC) from thoracic aorta of Sprague-Dawley rats were cultured and irradiated with gamma-ray. Cell viability was measured by direct cell counting and MTT assay, and flow cytometry was performed to measure fractional distributions of the cells. Gamma-ray irradiation inhibited cell proliferations accompanied with decreased G1 phase and increased S- and G2/M phases, and the maximum effects were observed at 1500 or 2000 cGy. Submaximal concentrations of antioxidants, such as allopurinol, vitamin C, N-acetylcycteine(NAC), lipoic acid, dihydrolipoic acid and rebamipide tended to increase the cell viability suppressed by low dose of radiation(500 cGy), and enalapril and vitamin E increased it significantly. Allopurinol, vitamin E, NAC, lipoic acid, captopril and enalapril significantly increased G1 phase. Allopurinol and vitamin E tended to increase c-Myc expression, detected by Western blot, that was reduced by the radiation, and enalapril increased it significantly. The cell viability and c-Myc expression were highly correlated(r=0.97) with each other. These results suggest that antioxidants, especially enalapril and vitamin E, recover the viability of VSMC from gamma-radiation injury, through a mechanism which includes increase of c-Myc protein expression.

• Journal of the Korean Society of Food Science and Nutrition
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• v.46 no.8
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• pp.1012-1017
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• 2017

Mesembryanthemum crystallinum (Family: Aizoaceae) is an annual plant consisting of ice crystal-shaped bladder cells, which is responsible for its common name ice plant. This study investigated biological activities according to general components and extraction solvent in order to examine the functionality of ice plant. The total content of free amino acids was 32.57 mg/g, including 4.64 mg/g of L-alanine as the most abundant and 2.60 mg/g of ${\gamma}$-aminobutyric acid. Regarding angiotensin converting enzyme inhibitory activities of solvent fractions of ice plant, ethyl acetate fraction and chloroform fraction showed activities of $33.17{\pm}3.20{\sim}88.19{\pm}3.20%$ and $23.72{\pm}2.89{\sim}86.78{\pm}2.24%$, respectively, similar to $Captopril^{(R)}$ ($19.51{\pm}3.44{\sim}84.72{\pm}1.06%$) and $Enalapril^{(R)}$ ($24.93{\pm}1.12{\sim}91.32{\pm}3.62%$) as positive control groups. Regarding inhibition of lipid droplet production in 3T3-L1 preadipocytes by ice plant, anti-adipogenic activities were $53.00{\pm}0.45{\sim}65.75{\pm}0.31%$ and $44.16{\pm}0.29{\sim}63.32{\pm}0.36%$ in the ethyl acetate fraction and butanol fraction, respectively, showing the lowest lipid droplet production. The chloroform fraction and hexane fraction showed activities of $38.33{\pm}0.09{\sim}56.55{\pm}0.50%$ and $31.17{\pm}0.50{\sim}55.10{\pm}1.93%$, respectively, whereas the water fraction showed activity of $26.32{\pm}2.27{\sim}49.48{\pm}0.05%$. Therefore, all solvent fractions inhibited fat accumulation of 3T3-L1 preadipocytes according to treatment concentration. According to the results above, it would be possible to utilize ice plant as a new health functional material.

• Childhood Kidney Diseases
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• v.1 no.2
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• pp.101-108
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• 1997

Purpose : The clinical characteristics of renovascular hypertension (RVHT) in children were analyzed. Methods : Medical records of 16 children diagnosed as RVHT on the basis of angiography during Jan. '86 to Jun. 94 in our hospital were reviewed retrospectively. Results : The mean age at the onset was 8.5 yrs and the sex ratio(M:F) was 7:9. The causes of RVHT were Takayasu arteritis in 6, Moyamoya disease in 5, and fibromuscular dysplasia in 3 patients. Abdominal bruit was noted in 6 patients (38%). Peripheral renin activity was raised in all tested patients. Bilateral renal arterial involvemnent was found in 9 patients (56%). Captopril renal scans showed good correlation with angiographic findings. Five patients were treated with antihypertensives only, and blood pressure was controlled completely in 2 and incompletely in 3. Percutaneous transluminal angioplasty was performed in 10 patients with 50% of success rate. However, hypertension was recurred due to restenosis or accompaning aortic stenosis in 3 patients. Surgical treatment was performed in 4 patients, and the blood pressure was controlled partially in 1 and poorly in the remaining 3. Conclusions : Takayasu arteritis, Moyamoya disease and fibromuscular dysplasia are the major causes of childhood RVHT in our country. The diagnosis of RVHT in children should be based on a set of tests individually selected for case by case. For the low curability of the current treatment modalities available, RVHT in children should not be regarded as 'curable' so far. We expect, however, that the outcome will be improved by more extensive application of the newly developed surgical technique.

• Radiation Oncology Journal
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• v.22 no.1
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• pp.25-32
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• 2004

Purpose : Evaluate the efficacies and toxicities of concurrent chemoradiotherapy (CCRT), with or without intraluminal brachytherapy (ILB), using a retrospective analysis in esophageal carcinomas with respect to survival. Materials and Methods : From April 1995 to July 2001, a total of 65 patients, diagnosed with an esophageal carcinoma, were treated by CCRT, with 21 also treated by ILB after CCRT. External radiotherapy was peformed using 6 or 10 MV X-rays, with a dose range of $46.8~\69.6$ Gy (median; 59.4). The ILB was peformed using high-dose-rate brachytherapy with Ir-192. The fractionation of ILB was 3 Gy by 4, or 5 Gy by 2 fractions. Cisplatin $(75\;mg/m^2)$ was given on each first day of weeks 1, 5, 9 and 13, and 5-FU $(1,000\;mg/m^2)$ as a continuous infusion for the first 4 days of each course. Results : The median survival time of all patients was 15 months, and the 1, 2 and 3-year survival rates were 55.4, 29.2 and $20.7\%$, respectively. The 2-year survival rates of the patients with and without ILB were 33.3 and $27.3\%$, respectively (p=0.80). The 2-year survival rates of the patients with a complete, partial and no response were 44.1, 13.8 and $0\%$, respectively (p=0.02). The response to treatment was the only significant factor affecting the overall survival from a multivariate analysis. Conclusion : This study has shown that the survival outcomes of CCRT were much better than previous results with radiotherapy alone. However, the addition of ILB after CCRT showed no advantage over that of CCRT alone.

• Childhood Kidney Diseases
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• v.3 no.2
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• pp.232-236
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• 1999

IgA 신병증은 사구체 중맥에 IgA가 침착하는 것이 특징적인 질환이며 막성 사구체 신염은 IgG가 사구체 기저막의 상피하에 미만성으로 침착하는 질환이다. 원발성 사구체 질환중 IgA 신병증과 막성 사구체신염은 비교적 흔한 질환이나 전체적인 빈도는 낮은 편으로, 한 환자의 사구체에서 두 질환이 동시에 발생하는 경우는 매우 드물다. IgA 신병증과 막성 사구체신염의 중복 신염은 Doi등이 1983년 원발성 신질환으로서 처음 보고한 이래, 성인에서 20여례가 보고되었다. 저자들은 신증후군이 발생한 환아에서 신생검을 시행한 결과 원발성 신질환으로서 IgA 신병증과 막성 사구체신염의 소견이 동시에 보이는 중복신염의 드문 예를 경험하였기에 보고하는 바이다. 환아는 7세된 남아로 내원 한달 전부터 발생한 전신부종을 주소로 내원하였다. 가족력과 과거력상 특이 소견없었으며, 내원시 이학적 소견상 전신적인 허약감과 안와부종, 복부팽만, 하지의 함요부종이 관찰되었고, 검사소견에서는 WBC $19,800/mm^3$, Hb 14.1g/dL, Platelet $397,000/mm^3$, BUN/Cr 10/0.4mg/dL, protein/albumin 4.43/2.73g/dL, cholesterol 429mg/dL, IgA 85mg/dL, $C_3$ 68.8mg/dL, $C_4$ 13.4mg/dL, ANA(-), ANCA(-), RF(-), HBsAg/Ab(-/-)이었다. 뇨검사에서는 RBC many/HPF, WBC 2-3/HPF, protein ${\le}\;300mg/dL$ 였으며, 24시간 소변 검사상 protein 9.18g/day, Ccr 66.67ml/min의 소견을 보였다. 신생검을 시행한 결과 광학현미경상에서 몇몇 사구체의 분절성 경화와 중맥역의 증식이 관찰되었고, 면역형광현미경검사에서는 IgA(3+)가 과립상으로 미만성 분포를 보이며 중맥역에 침착되어 있고, 미세한 과립상과 위선의 양상으로 IgG(1+)가 모세혈관벽에 침착되어 있었으며, 전자현미경 소견상 중맥역과 모세혈관 기저막 상피하에 소량의 전자 고밀도 침착이 함께 관찰되었다. 환아는 prednisolone을 경구 투여 받았으나 단백뇨와 혈뇨가 지속되어 solumedrol pulse therapy, captopril과 cyclophophamide로 치료 받은 후, 전신 상태 호전되고, 혈뇨가 사라졌으며, 24시간 소변 검사상 단백뇨가 487.5mg/day로 감소하여 외래에서 추적 관찰 중이다.