• Journal of Acupuncture Research
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• v.40 no.2
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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.

• Proceedings of the PSK Conference
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• 2003.10b
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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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• v.27 no.7
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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.

• Korean Journal of Food Science and Technology
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• v.35 no.6
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• pp.1199-1203
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• 2003

Polyphenols were isolated from Korean green tea using Sephadex LH-20 and HPLC. The isolated polyphenols were procyanidin B-4, procyanidin B-2-3,3'-digallate, prodelphinidin C-2-3,3'-di-O-digallate, (+)-catechin-3-O-rhamnose, procyandin B-5, procyanidin B-7-3-0-gallate, gallate, 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 and (+)-taxifolin-3-O-D-xyloside. The inhibitory effects of prodelphinidin C-2-3,3'-di-O-gallate and procyanidin B-2-3,3'-digallate $(at\;100{\mu}M)$ on angiotensin.converting enzyme were 68.8 and 54.6%, respectively, while the inhibitory effects of prodelphinidin C-2-3,3'-di-O-gallated and procyanidin B-2-3,3'-digallate $(at\;100{\mu}m)$ on xanthine oxidase were 54.5 and 38.2%, respectively. Lastly, the inhibitory activities of prodelphinidin C-2-3,3'-di-O-gallate $(at\;100{\mu}m)$ on tyrosinase was 42.1%.

• Biomolecules & Therapeutics
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• v.28 no.1
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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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• v.50 no.4
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• pp.327-333
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• 2007

This study was conducted to examine antioxidant activities of Perilla frutescens var. acuta leaf. For the this purpose, DPPH radical scavenging activity, lipid oxidation inhibition, SOD-like activity, and xanthine oxidase inhibitor activity of water extract, ethanol extracts (30, 50, 70, and 95%) and the fractions obtained from these extracts were determined. The electron donating abilities of the chloroform fraction obtained from the 70% and 95% ethanol extracts were 50%, and that of the ethyl acetate fraction for all of the extracts was above 75%. In particular, the electron donating ability of the ethyl acetate fraction of the 70% ethanol extract showed the greatest activity with 200.5 ppm of $RC_{50}$ value. The 70% ethanol extract was most effective to inhibit the automatic oxidation of linoleic acid at $40^{\circ}C$ storage. The highest inhibition effects appeared in the chloroform and ethyl acetate fractions of the water extract, and the 30, 50, and 70% ethanol extracts, and the highest lipid oxidation inhibiting effect of the 95% ethanol extract occurred in the hexane and acetate fractions. The SOD-like activity of the water extract was 30.3%, and the activities of the various concentration of ethanol extracts were 28-32% and the activity of the 70% ethanol extract was the highest. The SOD-like activity of the ethyl acetate fraction of the 70% ethanol extract was highest with 1,549.0 ppm of $RC_{50}$ value. Xanthine oxidase inhibition activity was greatest in the water extract and the activities of the ethanol extracts were 36-41.2%. The xanthine oxidase inhibition activity of the ethyl acetate fraction of the water extract was highest. In summary, we found that electron donating ability, lipid oxidation inhibition, and SOD-like activity of Perilla frutescens var. acuta leaf were greatest in the ethyl acetate fraction of the 70% ethanol extract, and xanthine oxidase inhibition activity was highest in the ethyl acetate fraction of the water extract.

• Applied Biological Chemistry
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• v.47 no.1
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• pp.92-95
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• 2004

Biological activities and anticarcinogenicity of Korean Pear peel were investigated, Electron donating activity and superoxide dismutase (SOD)-like activity of fraction II, III were up to 80% and 50-60% at 50 ppm, respectively, Inhibitory effects on xanthine oxidase were about 80% at 50 ppm, breast adenocarcinoma was about 60% at 2,000 ppm, higher III than II Inhibitory effect on prostate adenocarcinoma was about 23% at 500 ppm. In conclusion, Korean pear peel was expected to use as a functional material.

• Applied Microscopy
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• v.25 no.3
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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.

• Journal of the Korean Society of Food Science and Nutrition
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• v.45 no.11
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• pp.1610-1616
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• 2016

This study aimed to establish an optimal extraction process and high performance liquid chromatography-ultraviolet (HPLC-UV) analytical method for determination of 3,5-dicaffeoylquinic acid (3,5-DCQA) as a part of materials standardization for the development of a xanthine oxidase inhibitor as a health functional food. The quantitative determination method of 3,5-DCQA as a marker compound was optimized by HPLC analysis using a Luna RP-18 column, and the correlation coefficient for the calibration curve showed good linearity of more than 0.9999 using a gradient eluent of water (1% acetic acid) and methanol as the mobile phase at a flow rate of 1.0 mL/min and a detection wavelength of 320 nm. The HPLC-UV method was applied successfully to quantification of the marker compound (3,5-DCQA) in Aster glehni extracts after validation of the method with linearity, accuracy, and precision. Ethanolic extracts of A. glehni (AGEs) were evaluated by reflux extraction at 70 and $80^{\circ}C$ with 30, 50, 70, and 80% ethanol for 3, 4, 5, and 6 h, respectively. Among AGEs, 70% AGE at $70^{\circ}C$ showed the highest content of 3,5-DCQA of $52.59{\pm}3.45mg/100g$ A. glehni. Furthermore, AGEs were analyzed for their inhibitory activities on uric acid production by the xanthine/xanthine oxidase system. The 70% AGE at $70^{\circ}C$ showed the most potent inhibitory activity with $IC_{50}$ values of $77.01{\pm}3.13{\sim}89.96{\pm}3.08{\mu}g/mL$. The results suggest that standardization of 3,5-DCQA in AGEs using HPLC-UV analysis would be an acceptable method for the development of health functional foods.

• Archives of Pharmacal Research
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• v.26 no.12
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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.