• Microbiology and Biotechnology Letters
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• v.24 no.2
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• pp.213-216
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• 1996

Optically active carboxylic acid, D-(-)-$\beta$-hydroxyisobutyric acid {(D)-(-)-HIBA} is a useful chiral starting material for the preparation of enantiomerically pure bioactive compounds which have a chiral methyl carbon center in the molecule such as captopril, $\alpha$-tocopherol, erythromycin A, muscone and so on. (S)-3-Acetoxy-2-methylpropanol can be used as the precursor of (D)-(-)-HIBA, that is, chemical oxidation of the hydroxyl group and subsequent hydrolysis of acyl group in (S)-3-acetoxy-2-methylpropanol affords D-(-)-$\beta$-hydroxyisobutyric acid. (S)-3-Acetoxy-2-methyl-propanol was prepared by lipase-catalyzed asymmetric hydrolysis. In the enzymatic hydrolysis system, lipase AY (Candida rugosa) provided the expected (S)-3-acetoxy-2-methylpropanol in 60% e.e. of the enantiomeric purity under the phosphate buffer and organic co-solvent system.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.81.1-81.1
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• 2003

Buprenorphine(BPN) is used to treat withdrawal syndromes in narcotic addictions. When narcotics are stopped, withdrawal syndromes such as pupil dilation and blood pressure increment are appeared. And BPN is often prescribed concomitantly with antihypertensives. We researched whether combined medicines of BPN and antihypertensives affected on the metabolism of BPN. After BPN was incubated with antihypertensives such as nifedipine, verapamil, captopril and propranolol in rat or human microsomes, amounts of BPN and its metabolite, norbuprenorphine (NBPN), were measured. (omitted)

• Journal of the Korean Society of Food Science and Nutrition
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• v.44 no.4
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• pp.483-490
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• 2015

The purpose of this study was to investigate the effects of 50% ethanol extracts of ripe black raspberry (Rubus occidentalis, RBR) on hypertension in spontaneously hypertensive rats (SHR). The final systolic blood pressure of the group treated with RBR for 12 weeks was significantly lower than that of the SHR group. The mRNA expression level of endothelial nitric oxide synthase (eNOS) was significantly decreased in SHR. However, treatment with RBR and captopril increased the level of eNOS mRNA in SHR. Moreover, plasma levels of homocysteine and plasminogen activator inhibitor-1 were significantly reduced by RBR. Plasma total cholesterol, high-density lipoprotein, and low-density lipoprotein cholesterol levels were lower in SHR than Wistar Kyoto rats (WKY). However, there was no significant difference in plasma triglyceride level between WKY and SHR. The number of eosinophilic cardiac muscle cells was reduced in heart muscles after treatment with captopril and RBR. Therefore, this study suggests that RBR extracts may be useful for improvement of hypertension.

• Journal of Life Science
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• v.28 no.2
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• pp.187-194
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• 2018

Eritadenine (EA), derived from Lentinus edodes (LE), reduced low-density lipoprotein (LDL), triglyceride (TG), and phospholipids in bloods, and fatty acid depositions in animals and humans. Previously, we reported that EA inhibited angiotensin-converting enzyme (ACE) activity in vitro. Now, we report that EA reduced blood pressures in spontaneous hypertension rats (SHR). EA-containing LE mycelial culture enzyme extract (EA-LEMSCEE) was prepared from LE mycelial solid cultures and the hot-water extract of LE fruit bodies. Both EA and EA-LEMSCEE inhibited ACE activity in immortalized human umbilical endothelial cells (EA.hy926). EA-LEMSCEE treatments (7.5 mg/kg, 22.5 mg/kg) significantly reduced systolic and diastolic blood pressure in SHR. At five weeks of treatment, EA-LEMSCEE treatment significantly reduced systolic and diastolic blood pressure, similar to the positive control (captopril, CP; 4 mg/kg) treatment. In addition, the LEMSCEE without EA decreased systolic and diastolic blood pressures compared to the control, but not significant. EA-LEMSCEE decreased renin and ACE activities, and angiotensin II (Ang II) contents in SHR compared to the control. After five weeks of treatment, the effect of EA-LEMCEE was similar to that of CP. These results indicate that EA and EA-LEMSCEE reduce blood pressure by inhibiting the renin and ACE activity of SHR. Furthermore, these results imply that EA or EA-LEMSCEE could be used as an antihypertension agent in humans.

• Journal of Life Science
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• v.28 no.11
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• pp.1290-1300
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• 2018

The glucosinolate content, antioxidant activity, and antihypertensive and antidiabetic activities were measured in a crude extract of Dolsan leaf mustard kimchi (DLMK). The glucosinolate content was low at 6.41 and 7.92 mg/g in leaves and stems of DLMK after 21 days of fermentation. The total polyphenol and total flavonoid contents were more than 2 times higher in the leaves (211.7 mg GAE/g, 158.8 mg QE/g) than in the stem (53.7 mg GAE/g, 85.2 mg QE/g) during the fermentation period. The 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) radical scavenging activity and electron donating ability (EDA) were similar to those of the control group after 14 days of fermentation, while the ferric reducing antioxidant power (FRAP) was higher in the leaves after 14 days of fermentation when compared to the control group. The angiotensin converting enzyme (ACE) inhibitory activity showed similar or higher inhibitory activity in the leaves when compared to the control group (0.01% captopril), and the ${\alpha}$-glucosidase inhibitory activity was higher in the leaves and stems when compared to the control group (0.05% acarbose). The glucosinolate content and the ABTS, ACE, and ${\alpha}$-glucosidase inhibitory activity were correlated, as determined by the observed straight line plot with a positive grade. During the fermentation period, the detected glucosinolates were sinigrin, glucobrasicin, glucotropeolin, and progoitrin. The DLMK extract is therefore expected to be valuable as a functional food because of its effective antioxidant, antihypertensive, and antidiabetic activities.

• Proceedings of the Korean Society for Bioinformatics Conference
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• 2005.09a
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• pp.249-255
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• 2005

Angiotensin-converting enzyme (ACE) is primarily responsible for human hypertension. Current ACE drugs show serious cough and angiodema health problems due to the un-specific activity of the drug to ACE protein. The availability of ACE crystal structure (1UZF) provided the plausible biological orientation of inhibitors to ACE active site (C-domain). Three-dimensional quantitative structure-activity relationship (3D-QSAR) models have been constructed using the comparative molecula. field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) for a series of 28 ACE inhibitors. 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 specific activity to ACE.

• The Journal of Internal Korean Medicine
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• v.32 no.2
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• pp.278-287
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• 2011

Objectives : The object of this study was to observe the nephroprotective effects of Sojongchobisunki-tang (SCST), which has traditionally been used as Korean medicine for treating various renal diseases, on cisplatin-induced rat acute renal failure. Methods : Three different dosages of SCST were orally administered once a day for 23 days before cisplatin treatment (5 mg/kg, single intraperitoneally administered) and 5 days after cisplatin treatment (once a day for 28 days). 6 groups, of 8 rats per group were used in the present study after 7 days of acclimatization. Changes of the body weight, kidney weight, serum BUN and creatinine levels were observed, as well as changes of the kidney MDA and GSH contents. The results were compared with captopril 100 mg/kg of which the effects on cisplatin-induced acute renal failures are already confirmed. Results : Acute renal failure induced by cisplatin were induced by oxidative stress and related lipid peroxidation in the present study. However, these acute renal failures and inhibition of antioxidant effects induced by cisplatin were dose-dependently reduced by treatment at all three different dosages of SCST extracts. Conclusions : This study suggests that SCST extracts showed favorable effects on the cisplatin-induced rat ARF.

• The Journal of Internal Korean Medicine
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• v.30 no.4
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• pp.821-831
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• 2009

Purpose : This study was to observe the nephroprotective effects of the traditional prescription, Daebuncheong-eum (DBCE). DBCE has generally been used for treating various renal diseases, including renal failure. Methods : Three different dosages of DBCE extract were orally administered once a day for 28 days. At the 23rd day after DBCE extract treatment, cisplatin was also treated. Then, 5 days after cisplatin treatment, all rats (6 groups of 8 rats each) were sacrificed. Changes on the body weight, kidney weight, serum BUN and creatinine levels were observed, along with changes to the kidney MDA and GSH contents. The results were compared with captopril 100mg/kg, from which the effects on cisplatin-induced acute renal failures have already been confirmed. Results : Cisplatin induced ARF are 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 of all three different dosages of DBCE extracts. Conclusion : This study suggests that DBCE extracts show favorable effects on cisplatin-induced rat ARF.

• Archives of Pharmacal Research
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• v.17 no.4
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• pp.263-268
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• 1994

This study was conducted to characterize the in vivo pharmacology of KR-30988, KR-30992 and losartan, new AT antagonists, given as i.v. cumulative doses, in two antimal models of high renin, conscious renal artery-ligated hypertensinve rats (RHRs) and nomotensive rats anesthetized with urethane (90 mg/kg, i.p.) and .alpha.-chloralose (90 mg/kg, i.p.), with a special emphasis on the phamacological characterization of the latter model. In conscious RHRs, KR-30988, KR-30992, losartan and captopril caused a dose-dependent decrease in blood pressure, their relative potencise ($ED_{20}$) being 0.057, 0.028, 0164 and 0.018 mg/kg, i.v., repectively. In anesthetized rats, 2 hours after anesthesia, plasma renin activity was increased from 7.31 tp 34.07 ng/ml/h, the level approximately 1.5 times greater than the highest level in RHRs. In anesthtized rats, the $ED_{20}$s for all four compounds were 0.004 mg/kg i.v., respectively. By comparison, $ED_{20}$sfrom anesthetized rats were 4 to 5 times smaller than those from conscious RHRs, with a good correlation (.gamma. = 0.999) noted between thetized rats to the hypotensive activity of the compounds and the same order of potencies intwo models. These results suggest that, in addition to PHRs, the normotensive rats anesthetized as above can serve as a suitable model for the rapid phamacological evaluation of $AT_1$ receptor antagonists.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1994.11a
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• pp.99-104
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• 1994

Renin-Angiotensin계는 정상 및 질병시의 혈압조절에 매우 중요한 역할을 담당하고 있음이 밝혀지면서, 이 조절계의 특정단계를 간섭함으로써 새로운 고혈압치료제를 개발하려는 연구가 일찍부터 시도되었다. (그림 1). 그 중에서 내인성 생리활성물질인 Angiotensin II의 합성을 차단하는 ACE 저해제는 임상적으로 고혈압 및 심부전치료제로서 유용성이 인정되어 현재 널리 사용되고 있다. ACE 저해제는 종종 마른기침, 발적과 같은 부작용이 나타나므로 이러한 부작용을 극복하려는 연구가 많이 있었으나 이는 작용기전에서 기인되는 것으로 해결에 한계를 보여왔다. 그런데 1982년 일본의 Takeda사의 연구진은 S-8307, 8308이라는 효과가 매우 약하기는 하지만 Angiotensin II 수용체를 선택적으로 차단하는 비펩타이드성의 AII길항물질을 특허 출원하였다. 미국의 Du Pont사는 AII길항약물이 효능은 그대로 유지하면서 ACE 저해제들의 부작용을 해결할 수 있을 것으로 예상하고 Takeda 화합물을 모핵으로하여, 많은 유도체들을 합성하면서 구조-활성 연구를 수행한 결과 비펩타이드성길항제인 Dup 753(Losartan, Cozaar$^{R}$) (2-N-butyl-4-chloro-5-hydroxymethyl-1-(2'-(1H-tetrazole-5-yl)biphenyl-4-yl) imidazole, potassium salt)을 발견하게 되었다. 이 Dup 753은 특별히 AII수용체중 혈압조절과 관련이 있는 AT1 수용체를 선택적으로 차단하는데, 효력은 ACE 저해제인 captopril과 유사하며, 경구흡수가 잘되고 지속시간이 길어 하루에 한번 먹는 경구제제로 개발되고 있는 것으로 알려져 있다. 이 Dup 753의 지속시간이 긴 것은 그 대사물인 Exp 3174에 기인하는 것으로 알려져 있으며, 대사체가 Dup 753에 비해 효력도 훨씬 더 높고 지속시간도 길어서, Dup 753은 일종의 prodrug적 개념이 들어있는 약물이라 할 수 있다.