• 동국한의학연구소논문집
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• 제11권
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• pp.66-73
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• 2008

Objectives: The study was designed to evaluate the single dose toxicity of modified Bo-yang-Hwan-o-Tang (mBHT) in Sprague-Dawley (SD) rats. Methods: The mBHT was once administrated orally to both sexes of rats at dose 2,000 mg/kg body weight which are the recommended maximum limit dose for acute toxicity. We recorded clinical signs of toxicity, body weight, gross and histological changes in target organs for all rats. Results: Neither significant changes of body weight not death was observed during the observation period in mBHT-administrated rats. Neither significant toxic signs not histopathological changes were shown during the observation period. There were not observed significant gross abnormality between the control and mBHT-administrated rats. Conclusions: These results indicated that the toxicity of mBHT is greater than 2,000 mg/kg body weight in SD rats.

• 한국식품과학회지
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• 제39권5호
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• pp.558-563
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• 2007

본 연구에서는 정상 세포인 간상피세포를 이용하여 BHT와 PG가 GJIC에 미치는 효과 및 그 작용 기전을 살펴보았다. BHT와 PG를 WB-F344세포에 각각 1.0mM, 0.75mM 이상 처리한 결과, 세포 생육이 80%이하로 저하되어 세포 독성을 보였고, BHT와 PG의 GJIC에 대한 억제효과는 이보다 낮은 농도인 0.6mM, 0.1mM에서 나타났으며 처리에 따른 Cx43 단백질의 발현 및 인산화를 측정한 결과, BHT와 PG 모두 농도의존적으로 Cx43의 인산화가 증가하였고, Cx43의 구조적 변화와 관련된 MAP kinase는 주요 biomarker인 ERK, p38, JNK의 발현 및 인산화를 측정한 결과, 농도의존적으로 ERK와 p38의 인산화가 증가하는 것으로 나타났다. 이는 WB-F344세포에 BHT와 PG의 처리가 세포독성을 나타내기 전 농도에서 GJIC의 억제하였음을 의미하며 이는 식품첨가물의 안전성 평가에도 활용될 수 있을 것으로 기대된다.

• Asian-Australasian Journal of Animal Sciences
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• 제23권10호
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• pp.1276-1281
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• 2010

The present study was conducted to investigate the effects of butylated hydroxytoluene (BHT) supplementation on diluted, cooled and frozen-thawed ram spermatozoa. After primary evaluation of collected ejaculates, only semen samples with motility of more than 70% and sperm concentration higher than $3{\times}10^3$ sperm/ml were used for cryopreservation. The selected semen samples were then pooled and diluted 1:4 with Tris Citrate Fructose Yolk (TCFY) extender supplemented with different concentrations of BHT (0.5, 10, 2.0 and 3.0 mM). As the control, semen was diluted and frozen in the diluent without BHT. Motility, progressive motility, viability, membranes and acrosome integrity were evaluated after dilution (part 1), cooling (part 2) and freezing and thawing (part 3). The results of the first part of the experiment showed that there were no significant difference between treatments in the motility, progressive motility, viability, membranes and acrosome integrity of spermatozoa, but the results with 2.0 mM BHT were slightly better than obtained with other levels of BHT and control extender. Significantly better results (p<0.05) were observed in the second part of the experiment for cooled spermatozoa characteristics, when extender was supplemented with 2.0 and 3.0 mM BHT. Furthermore, the results obtained in the third part of the experiment indicated that, after freezing and thawing, all evaluated semen characteristics were improved significantly (p<0.05) by increasing BHT levels, with the best results obtained for extender containing 2 mM BHT. Comparison of these results with those of control diluent, the effects of supplementation were significantly (p<0.01) better. However, the higher concentration of BHT (3.0 mM) reduced the motility, acrosomal integrity, viability and hypo-osmotic swelling response of spermatozoa compared to extender containing 2.0 mM BHT. In conclusion, the results obtained in this study showed that the semen quality of rams was improved when BHT was added to extender used before the freezing process.

• 대한본초학회지
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• 제27권6호
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• pp.83-90
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• 2012

Objectives : Modified Bo-Yang-Hwan-O-Tang (mBHT) is a polyherbal medicine of twelve herbs traditionally used in the treatment of cerebral and cardiac stroke and vascular dementia. The purpose of this study was to evaluate the neuroprotective effect, pyramidal neuronal cell, inflammation and apoptosis of mBHT against global ischemia in rats. Methods : Global ischemia was produced by two-vessel occlusion(2-VO) in SD male rats. mBHT at dose of 500 mg/kg was orally administrated for 2 weeks or 6 weeks after global ischemia. The histopathological changes of ischemic brain were observed by staining of hematoxylin and eosin (H&E) and Nissl and immunohistochemisty with anti-GFAP (glial fibrillary acidic protein) antibody as a astrocyte marker. The expression of inducible nitric oxide synthase (iNOS) and apoptotic proteins such as Bax, Bcl-2 and caspase-3 was determined by western blot. Results : mBHT treatment significantly inhibited the pyramidal neuronal loss in CA1 of hippocampus of global ischemic rats by 2-VO. mBHT also suppressed the activation of astrocytes in the CA1 at 6 weeks after ischemia. In addition, mBHT significantly increased the expression of anti-apoptotic protein, Bcl-2 on iscemic brain, and significantly attenuated the expression of apoptotic proteins, Bax and caspase-3. Conclusions : These results indicate that mBHT inhibits neuronal cell damage induced in global ischemia by 2-VO, suggesting that mBHT may be a potential candidate for the treatment of vascular dementia.

• Journal of Pharmaceutical Investigation
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• 제39권6호
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• pp.445-449
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• 2009

According to the statistical data, stroke is about 13.9% of leading causes of death. Some herbal medicines including Paeonia lactiflora, Angelica gigas nakai and Prunus persica, etc., had been reported to be effective in preventing stroke and mBHT (Modified BoyangHwanoTang) was an advanced prescription used in Korean clinics. Orally disintegrating tablets (ODT) is useful for patients suffering from dysphagia, motion sickness, repeated emesis and mental disorders. Further, drugs exhibiting satisfactory absorption through the mucosa intended for immediate pharmacological action could be advantageously formulated in ODT. The aim of this study was to develop the most efficient ODT formulation of mBHT. Corresponding herbal medicines comprising mBHT were extracted with water for 3 hr at 95~$100{^{\circ}C}$ and then dried. mBHT extract was obtained with about 30% of yield. Subsequently, some pharmaceutical excipients such as spray-dried lactose, crospovidone, glyceryl behenate and/or cogrinded-treated arabia gum were used to achieve an immediate disintegration of mBHT ODT in oral cavity. The requirements of ODT with mechanical strength sufficient to stand the rigors of handling and capability of disintegrating within a few seconds in contact with saliva are indispensable. mBHT ODT prepared by the wet granulation method showed a disintegration time of below 30 sec.

• Journal of Acupuncture Research
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• 제27권4호
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• pp.29-38
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• 2010

Objectives : The purpose of the study is to determine the neuroprotective effect of modified Boyanghwano-tang(mBHT), a traditional Korean medicine, on the transient focal cerebral ischemia in rats. Methods : Focal ischemia and reperfusion were induced by middle cerebral artery occlusion(MCAO) for 90 min, followed by 144 h reperfusion in rats. mBHT(200mg/kg body weight, p.o.) was administrated in rats once a day during reperfusion. At the end of treatment, brain infarction was measured by TTC staining, and histological change was observed by H&E staining. The expressions of Bax, Bcl-2 and cytochrome c in ischemic brains were determined by immunofluorescent analysis. Results : mBHT significantly reduced the cerebral infarct volumes of the MCAO rats. mBHT also attenuated the neuronal cell death and the expressions of pro-apoptotic molecules, bax and cytochrome c in ischemic brains. Further, mBHT significantly increased the survival time of ischemeic rats and the expression of anti-apoptotic molecule, Bcl-2 in ischemic brains. Conclusions : Our results suggest that mBHT is neuroprotective and may prove to be useful adjunct in the treatment of ischemic stroke.

• 대한본초학회지
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• 제24권4호
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• pp.173-179
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• 2009

Objectives : In this study, the effects of different fractions isolated from modified Boyanghwanotang(mBHT) extract on LPS-induced inflammation in BV2 microglial cells were investigated. Methods : mBHT was extracted with water, and then fractionated with n-hexane, methylene chloride, ethylacetate and n-butanol. BV2 cells, a mouse microglia line were incubated with different concentrations of each fraction of mBHT for 30 min, and then stimulated with LPS for 24 h. Cell toxicity was determined by MTT assay. The concentration of nitric oxide (NO) was measured in culture medium by Griess reagent assay. The expression of inducible nitric oxide synthease (iNOS) protein was determined by Western blot. Results : Four fractions of mBHT were significantly inhibited LPS-induced NO productions in BV2 cells in a dose-dependent manner. The methylene chloride fraction of mBHT was most strongly inhibited the NO production compared with those of the others. The methylene chloride fraction of mBHT was also suppressed LPS-induced iNOS expression comparison of other fractions at same concentration ($50\;{\mu}g/ml$) in BV2 cells. Conclusions : The results showed that the methylene chloride fraction of mBHT may have an strong anti-inflammatory property through the inhibition of NO production and iNOS expression in activated microglia, and could a therapeutic potential for the treatment of various brain inflammatory diseases.

• 한국식품과학회지
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• 제13권4호
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• pp.273-282
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• 1981

콩기름기질(基質)과 에멀젼기질(基質)에서 반응(反應) 2 및 30시간(時間) 후(後)의 Maillard형(型) 갈색화반응액(褐色化反應液)에서 얻은 에탄올 추출물(抽出物)(M-2와 M-30, 각각 10 ml과 BHA, BHT, TBHQ와 ascorbyl palmitate (각각 0,02%, w/w)의 산화방지효과(酸化防止效果)를 비교(比較)하고저 하였다. Control 및 각(各) 기질(氣質)은 $45.0{\pm}0.5^{\circ}C$에서 저장(貯藏)되었으며, 5일(日)마다 과산화물(過酸化物)값과 TBA값을 측정(測定)하였다. 그 결과(結果)는 다음과 같다. 주로 POV 측정결과(測定結果)에 의거한 무수기질(無水氣質)에서의 산화방지효과(酸化防止效果)의 순서(順序)는 As. palmitate, TBHQ >> M-30, M-2 > BHT, TBHQ ,BHA 였으며, 에멀전기질(基質)에서의 순서(順序)는 As. palmitate >> M-30, M-2 > BHT, TBHQ, BHA였었다. 한편, Maillard형(型) 갈색화반응(褐色化反應) 추출물(抽出物)들은 무수기질(無水基質)에서 보다는 에멀전 기질(基質)에서 더 효과적(效果的)이었으며, 에멀전 기질(基質)에서는 그 효과(效果)는 phenol계(系) 산화방지제(酸化防止劑)인 BHT, TBHQ, BHA 보다 더 컸었다.

• 한국식품저장유통학회지
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• 제9권3호
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• pp.351-355
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• 2002

목초액의 아질산염 소거, 전자공여작용 및 대두유에 농도별(0.5, 1 및 5%)로 첨가하여 항산화성을 조사하였다. 아질산염 소거 효과는 모든 농도에서 pH가 증가하면서 감소하는 경향을 보였고, pH 1.2의 경우 100 ${\mu}\ell$/mL의 농도에서 80%이상의 높은 활성을 보였다. 전자공여작용은 50 ${\mu}\ell$/mL의 농도에서 약 80%의 효과를 나타내었다. 목초액을 첨가하지 않은 대두유를 control로 사용하였고, 0.1% BHT를 첨가한 대두유는 비교군으로 사용하여 5$0^{\circ}C$에서 10일간 저장하면서 실험을 하였다. 과산화물가는 목초액 1%와 5% 첨가군이 control과 BHT 첨가군보다 낮게 나타났으며, TBA가는 5% 목초액에서 가장 낮았고, 1% 목초액, 0.1% BHT 및 0.5% 목초액 첨가군 순으로 나타났다. 산가는 5% 목초액 첨가군이 가장 낮았고, 0.1% BHT, 1% 및 0.5% 목초액의 순으로 낮게 나타났다.

• Toxicological Research
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• 제5권1호
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• pp.9-15
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• 1989

The effect of butylated hydroxytoluene (BHT) and its major metabolite, 3, 5-di-tert-butyl-4-hydroxybenzoic acid (BHT-acid) on the uptake of taurocholate into hepatocytes was studied using the primary culture of rat hepatocytes. Hepatocyte were isolated by an in situ collagenase perfusion technique and maintained as a monolayer in serum-free meadia for 24 hours before use. The uptake of taurocholate was saturable with an apparent Km of 12.8+2.8 MuM and Vmax of 0.18+0.01 nmol/mg/min. Both BHT and BHT-acid inhibited the hepatocellular uptake of taurocholate when they were added to the culture.