• Journal of Acupuncture Research
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• 제40권2호
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• pp.135-142
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• 2023

Background: This study aimed to investigate hyperuricemia, renal inflammation, and xanthine oxidase (XO) activity improvement in a rat model treated with Scutellaria baicalensis extract (SBE). Methods: The rats were divided into 4 groups (n = 5 each), including sham, potassium oxonate (PO) injected hyperuricemia (control group), PO + 10 mg/kg allopurinol administrated (allopurinol group), and a PO + 50 mg/kg SBE administrated (SBE group), to investigate the effectiveness and molecular mechanisms of SBE. The effects of SBE on PO-induced hyperuricemia rats, renal inflammation, and XO activity were measured. Body weight and organ index of the kidney and liver were measured in PO-induced hyperuricemia rats, and serum uric acid level was extracted from whole blood and was measured. Renal inflammation was observed under a microscope after sections. XO activity was measured by liver tissue and serum XO levels. Results: Organ indexes of the kidney and liver in rats were significantly decreased in the allopurinol group than in the control group and with no significant difference in the SBE group. A PO injection for 5 days significantly increased serum uric acid levels in the control group compared to the sham group. Meanwhile, the SBE and allopurinol groups have significantly decreased serum uric acid levels compared to the control group. The SBE group revealed effectively improved renal histopathological changes compared to the control group. The XO inhibitor, allopurinol, significantly decreased XO activity. Additionally, SBE significantly lowered XO activity in rats. Conclusion: SBE can be used as an effective treatment for gout in the future.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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• pp.192.2-192.2
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• 2003

Apigenin-7-O-${\beta}$-D-glucoside, chrysoeriol, and luteolin were isolated from the aqueous ethanolic extract of Zostera marina L. leaves as the scavengers of reactive oxygen species (ROS) with the SC$\_$50/ values of 0.18 mM, 0.68 mM, and 0.18 mM against 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 0.04 mM, 0.03 mM, and 0.01 mM against superoxide radicals in the xanthine/xanthine oxidase system, respectively. The luteolin suppressed the expression of matrix metalloproteinase-1 (MMP-1) up to 44% at 4.0 ${\mu}$M. (omitted)

• Archives of Pharmacal Research
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• 제27권7호
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• pp.683-692
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• 2004

Curcumin (diferuloylmethane) is a major naturally-occurring polyphenol of Curcuma species, which is commonly used as a yellow coloring and flavoring agent in foods. Curcumin has shown anti-carcinogenic activity in animal models. Curcumin possesses anti-inflammatory activity and is a potent inhibitor of reactive oxygen-generating enzymes such as lipoxygenase/cyclooxygenase, xanthine dehydrogenase/oxidase and inducible nitric oxide synthase; and an effective inducer of heme oxygenase-1. Curcumin is also a potent inhibitor of protein kinase C(PKC), EGF(Epidermal growth factor)-receptor tyrosine kinase and LĸB kinase. Subsequently, curcumin inhibits the activation of NF(nucleor factor)KB and the expressions of oncogenes including c-jun, c-fos, c-myc, NIK, MAPKs, ERK, ELK, PI3K, Akt, CDKs and iNOS. It is proposed that curcumin may suppress tumor promotion through blocking signal transduction path-ways in the target cells. The oxidant tumor promoter TPA activates PKC by reacting with zinc thiolates present within the regulatory domain, while the oxidized form of cancer chemopreventive agent such as curcumin can inactivate PKC by oxidizing the vicinal thiols present within the catalytic domain. Recent studies indicated that proteasome-mediated degradation of cell proteins playa pivotal role in the regulation of several basic cellular processes including differentiation, proliferation, cell cycling, and apoptosis. It has been demonstrated that curcumin-induced apoptosis is mediated through the impairment of ubiquitin-proteasome pathway. Curcumin was first biotransformed to dihydrocurcumin and tetrahydrocurcumin and that these compounds subsequently were converted to monoglucuronide conjugates. These results suggest that curcumin-glucuronide, dihydrocurcumin-glucuronide, tetrahydrocurcumin-glucuronide and tetrahydrocurcumin are the major metabolites of curcumin in mice, rats and humans.

• 한국식품과학회지
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• 제35권6호
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• pp.1199-1203
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• 2003

한국산 녹차를 70% 에탄올로 추출한 후 Sephadex LH-20과 HPLC를 사용하여 polyphenol을 분리동정하였고 분리된 각 성분들의 angiotensin converting enzyme(ACE) 및 xanthine oxidase, tyrosinase의 저해효과를 확인하였다. 녹차로부터 HPLC로 polyphenol을 분리한 결과 epiafzelechin-$(4{\beta}{\rightarrow}8)$-epiafzelechin, procyanidin B-3-3-O-rhamnose, afzelechin-$(4{\alpha}{\rightarrow}8)$-catechin, prodelphinidin B-5-3,3'-di-O-digallate, (+)-taxifolin-3-O-D-xyloside 등 11종류를 분리하였다. ACE의 저해효과는 prodelphinidin-C-2-3,3'-di-O-gallate $100{\mu}M$에서 68.8%, procyanidin B-2-3,3'-digallate가 54.6%의 저해를 나타내었고, Xanthine oxidase는 prodelphinidin C-2-3,3'-di-O-gallate가 54.5%, procyanidin B-2-3,3'-digallate가 38.2%로 높은 저해효과를 보였다. Tyrosinase의 저해효과는 $100{\mu}M$ 농도에서 prodelphinidin C-2-3,3'-di-O-gallate가 42.1%, procyanidin B-2-3,3'-digallate와 procyanidin B-7이 각각 30.7%, 20.5%의 저해를 나타내었다. 따라서 녹차 추출물로부터 분리한 polyphenol이 혈압예방, 통풍 및 미백효과의 기능성 식품 신소재로서 이용이 가능하다는 것을 확인하였다.

• Biomolecules & Therapeutics
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• 제28권1호
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• pp.25-33
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• 2020

Several recent studies have reported that reactive oxygen species (ROS), superoxide anion and hydrogen peroxide (H₂O₂), play important roles in various cellular signaling networks. NADPH oxidase (Nox) isozymes have been shown to mediate receptor-mediated ROS generation for physiological signaling processes involved in cell growth, differentiation, apoptosis, and fibrosis. Detectable intracellular levels of ROS can be induced by the electron leakage from mitochondrial respiratory chain as well as by activation of cytochrome p450, glucose oxidase and xanthine oxidase, leading to oxidative stress. The up-regulation and the hyper-activation of NADPH oxidases (Nox) also likely contribute to oxidative stress in pathophysiologic stages. Elevation of the renal ROS level through hyperglycemia-mediated Nox activation results in the oxidative stress which induces a damage to kidney tissues, causing to diabetic nephropathy (DN). Nox inhibitors are currently being developed as the therapeutics of DN. In this review, we summarize Nox-mediated ROS generation and development of Nox inhibitors for therapeutics of DN treatment.

• Applied Biological Chemistry
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• 제50권4호
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• pp.327-333
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• 2007

본 연구에서는 차조기의 30, 50, 70, 95% 에탄올 및 물추출물과 분획물의 전자 공여능, 지질산화 억제능, SOD 유사활성 및 xanthin oxidase 저해 활성을 측정하였다. 추출물의 전자 공여능은 $18{\sim}30%$ 정도로 낮았으나, 분획물에서는 95%과 70% 에탄올 추출물의 chloroform 분획이 50% 수준의 활성을 보였고, ethyl acetate 분획에서는 모든 추출용매에서 75% 이상의 활성을 보였다. 특히, 70% 에탄올 추출물의 ethyl acetate 분획물이 93.4%로 가장 높은 활성을 보였으며 $RC_{50}$에 요구되는 농도는 200.5 ppm이었다. 저장 온도 $40^{\circ}C$에서 linoleic acid의 자동산화를 가장 효과적으로 억제하는 것으로 나타난 추출물은 70% 에탄올 이었다. 분획물의 경우, 95% 에탄추출물은 hexane과 ethyl acetate 가용성분이 그 외 에탄올 추출과 물추출은 chloroform과 ethyl acetate 가용성분이 가장 높은 억제효과를 나타내었다. SOD 유사활성은 에탄올 추출물이 $28{\sim}32%$, 물추출물이 30.3%이었으며, 70% 에탄올 추출물이 32.4%로 가장 높았다. 분획물에서는 70% 에탄올 추출물의 ethyl acetate 가용분이 38.8%로 활성이 가장 높았으며 $IC_{50}$에 요구되는 농도는 1549.0ppm이었다. Xanthine oxidase 저해 활성은 에탄올추출물이 $36{\sim}41.2%$이었으며, 물추출물이 46.9%로 추출물중 가장 높았다. 분획물에서는 물추출의 ethyl acetate 가용분이 1,000 ppm 농도에서 52%의 활성을 보여 가장 높았다.

• Applied Biological Chemistry
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• 제47권1호
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• pp.92-95
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• 2004

한국산 배과피의 기능성 원료로서의 가능성을 알아보기 위하여 폴리페놀 성분을 분획하여 그 생리활성 및 암세포증식능에 대하여 살펴보았다. 전자공여능에서는 50 ppm에서 분획물 II, III에서 80% 이상으로 나타났으며 SOD 유사능은 분획물 II, III의 500 ppm군에서 50-60%의 효과가 인정되었다. 통풍과 관련있는 xanthin oxidase 실험에서는 분획물 I의 저해 효과는 미미하였으나 II와 III에서는 50 ppm에서도 80%에 이르는 높은 저해효과가 관찰되었으며, 유선암세포(MDA) 생육억제 실험에서는 분획물 II보다 III가 높은 증식억제능을, 2,000 ppm에서는 약 60%의 억제능을 나타내었고, 전립선암(PC-3)의 세포억제효과에서는 III보다 II에서 오히려 억제 효과가 높았고, 500 ppm에서 약 23%의 억제효과가 관찰되어 한국산 배과피의 기능성 소재로서의 가능성을 확인할 수 있었다.

• Applied Microscopy
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• 제25권3호
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• pp.51-62
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• 1995

It has been well known that ischemia and reperfusion injury to skeletal muscle following an acute arterial occlusion causes significant morbidity and mortality. The skeletal muscle, which contains high energy phosphate compounds, has ischemic tolerance. During the ischemia, the ATP is catalyzed to hypoxanthine anaerobically and hypoxanthine dehydrogenase is converted to xanthine oxidase. During reperfusion, the hypoxanthine is catalyzed to xanthine by xanthine oxidase under $O_2$, presence and that results in production of cytotoxic oxygen free radicals. These cytotoxic free radicals, $O_2^-,\;H_{2}O_2,\;OH^-$, are toxic and make lesions in skeletal muscle during reperfusion. The authors perform the present study to investigate the effects of allopurinol, the inhibitor of xanthine oxidase, on reperfused ischemic skeletal muscles by observing the ultrastructural changes of the muscle fibers. A total of 48 healthy Sprague-Dawley rats weighing from 200 g to 250 g were used as experimental animals. Under urethane(3.0mg/kg., IP) anesthesia, lower abdominal incision was done and the left common iliac artery were ligated by using vascular clamp for 1, 2 and 6 hours. The left rectus femoris muscles were obtained at 6 hours after the removal of vascular clamp. In the allopurinol pretreated group, 50mg/kg of allopurinol was administered once a day for 2 days and before 2 hours of ischemia. The specimens were sliced into $1mm^3$ and prepared by routine methods for electron microscopic observations. All preparations were stained with uranyl acetate and lead citrate, and then observed with Hitachi -600 transmission electron microscope. The results were as follows: 1. In 1 hour ischemia/6 hours reperfused rectus femoris muscles of rats, decreased glycogen particles and electron density of mitochondrial matrix and dilated terminal cisternae are seen. In 2 hours ischemia/6 hours repersed rectus femoris muscles of rats, mitochondria with electron lucent matrix, irregularly dilated triad and spheromembranous bodies are observed. In 6 hours ischemia/6 hours reperfused rectus femoris muscles of rats, irregularly arranged myofibrils, and many spheromembranous bodies, fat droplets and lysosome are seen. 2. In 1 hour ischemia/6 hours reperfused rectus femoris muscles of rats pretreated with allopurinol, decreased glycogen particle and dilated cisternae of sarcoplasmic reticulum and triad are observed. In 2 hours ischemia/6 hours reperfused rectus femoris muscles of rats pretreated with allopurinol decreased electron density of mitochondrial matrix and spheromembranous bodies are seen. In 6 hours ischemia/6 hours reperfused rectus femoris muscles of rats pretreated with allopurinol, mitochondria with electron lucent matrix, spheromembranous bodies and dilated cisternae of sarcoplasmic reticulum and terminal cistern are observed. The results suggest that the allopurinol attenuates the damages of the skeletal muscles of rats during ischemia and reperfusion.

• 한국식품영양과학회지
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• 제45권11호
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• pp.1610-1616
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• 2016

섬쑥부쟁이로부터 고요산혈증 개선에 도움을 주는 기능성 식품 개발을 위하여 최적의 에탄올 추출물 탐색과 high performance liquid chromatography-ultraviolet(HPLC-UV) 분석방법에 의한 validation을 실시하였다. 지표성분으로 3,5-dicaffeoylquinic acid(3,5-DCQA)를 선정하여 표준화를 실시하였으며 검출법 확립을 위한 3,5-DCQA 정량분석은 Luna RP-18 칼럼($4.6{\times}250mm$, $5{\mu}m$)을 이용하여 1% 초산용액과 메탄올을 전개용매로 사용하였다. 용출은 1.0 mL/min의 유속으로 기울기 용출(gradient elution) 방법을 이용하였으며, 320 nm 파장에서 검출한 피크 면적을 이용하여 검량곡선을 작성하여 분석하였다. 본 연구에서 확립한 분석법으로 특이성, 직선성, 정밀성, 정확성, 회수율을 검색하였다. 3,5-DCQA의 검량선으로부터 상관계수($R^2$) 0.9999의 우수한 직선성과 intra-day와 inter-day 분석에서 90% 이상의 회수율과 5% 미만의 RSD를 나타내 정밀성과 정확성을 입증하였다. 검출한계는 $2.68{\mu}g/mL$였고 정량한계는 $8.11{\mu}g/mL$로 나타났다. 섬쑥부쟁이 에탄올 추출물(AGE)은 70과 $80^{\circ}C$에서 30, 50, 70, 80% 에탄올로 3, 4, 5, 6시간 동안 각각 추출하였으며, 지표물질의 검량곡선을 활용하여 각각의 AGE로부터 3,5-DCQA의 함량을 분석하였다. 본 시험법으로 분석한 3,5-DCQA의 함량은 $70^{\circ}C$에서 추출한 70% AGE가 $52.59{\pm}3.45mg/Aster$ glehni 100g의 함량을 나타내 가장 우수하게 나타났다. 그러나 섬쑥부쟁이 추출물에 함유된 5-caffeoylquinic acid(5-CQA)의 함량 비교분석은 에탄올 함량이나 추출 시간에 따른 함량 변화가 미미하게 나타났다. 또한, 다양한 AGE에 대하여 XOD 저해 효능을 검색하였을 때, 3,5-DCQA의 함량이 가장 높은 $70^{\circ}C$에서 추출한 70% AGE에서 우수한 효능을 나타내 기능성 원료 표준화를 위한 적합한 분석법임이 검증되었다. 따라서 본 연구를 통하여 확립된 3,5-DCQA의 분석법은 섬쑥부쟁이 에탄올 추출물로부터 개별인정형 건강기능식품 기능성 원료 개발을 위한 유용한 자료로 활용될 것으로 생각한다.

• Archives of Pharmacal Research
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• 제26권12호
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• pp.1024-1028
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• 2003

A prolyl endopeptidase inhibitor was isolated from the ethyl acetate soluble fraction of Phyllanthus ussurensis. The active compound was identified as an ellagitannin, corilagin. It was shown to non-competitively inhibit prolyl endopeptidase (PEP) with the $IC_{50}$ value of $1.17 \times $10^{-6}\mu$M. The Ki value was $6.70 \times 10^{-7}$ M. Corilagin was less inhibitory to other serine proteases such as chymotrypsin, trypsin, and elastase, indicating that it was relatively a specific inhibitor of PEP. Corilagin also effectively inhibited reactive oxygen species such as hydroxide and superoxide anion radical, hydrogen peroxide, and DPPH. Especially, corilagin showed potent scavel1ging activity on the superoxide anion radical in the ESR method ($IC_{50} =3.79 \times 10^{-6}$M) as well as xanthine oxidase system.