• Title/Summary/Keyword: repeated dose

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Exocrine Pancreatic Secretion in Response to Electrical Stimulation of Reticular Formation in Mesencephalone in Rats (흰쥐에서 중뇌망상체의 전기자극이 췌장액 분비에 미치는 영향)

  • Park, Hyoung-Jin;Lee, Yun-Lyul;Kwon, Hyeok-Yil;Shin, Won-Im
    • The Korean Journal of Physiology
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    • v.20 no.1
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    • pp.1-7
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    • 1986
  • It has been well documented that the peripheral autonomic nervous system plays an important role in exocrine pancreatic secretion. However, the role of the central nervous system in pancreatic function is still obscure even though the central nervous system has been known to control gastrointestinal functions through the autonomic nervous system. Since the reticular formation in the mesencephalone seems to integrate the autonomic function, the present study was undertaken to investigate a possible influence of the reticular formation upon the exocrine pancreatic secretion. Twenty·two albino rats fasted for 24 hours were anesthetized by intraperitoneal injection of urethane in a dose of 1 g/kg, The pancreatic duct was cannulated to collect pancreatic juice and bile juice was diverted to the jejunum. The gastroduodenal junction was ligated to Prevent passage of gastic juice into the duodenum. A pair of electrodes were bilaterally inserted in the reticualr formation of the mesencephalone with aid of a stereotaxic apparatus. When the volume of pancreatic juice secreted for 10 min became constant, the reticular formation was electrically stimulated for 10 min. Parameters of the electical stimulation was 1.3V, 40 Hz and 2 msec. When the pancreatic secretion returned to the level before the electrical stimulation, cervical vagotomy (11 rats) or administration of propranolol (11 rats) in a dose of 0.1 mg/kg through the jugular vein was carried out. Ten minutes after the treatment, the electrical stimulation of the reticular formation was repeated. The brain was fixed by perfusion of 10% formaline solution through the heart, and then placement of the electrode tip was examined histologically. Protein concentration and amylase activity in samples of Pancreatic secretion were measured. The electrical stimulation of the reticular formation significantly increased in volume $({\mu}l/10\;min)$, Protein output $({\mu}g/10\;min)$ and amylase output (U/10 min) in the pancreatic secretion. The stimulatroy effects were not affected by the cervical vagotomy but completely abolished by propranolol. Meantime, it was also observed that both vagotomy and propranolol significantly reduced the pancreatic secretory function. These results indicate that the reticular formation in the mesencephalone may exert a stimulatory effect upon the Pancreatic secretory function not through the vagus nerve but through the sympathetic pathway in anesthetized rats.

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Effect of $H_2O_2$ on Alveolar Epithelial Barrier Properties (폐상피세포 장벽에 대한 $H_2O_2$의 영향)

  • Suh, Duk-Joon;Cho, Se-Heon;Kang, Chang-Woon
    • Tuberculosis and Respiratory Diseases
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    • v.40 no.3
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    • pp.236-249
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    • 1993
  • Background: Among the injurious agents to which the lung airspaces are constantly exposed are reactive species of oxygen. It has been widely believed that reactive oxygen species may be implicated in the etiology of lung injuries. In order to elucidated how this oxidant causes lung cell injury, we investigated the effects of exogenous $H_2O_2$ on alveolar epithelial barrier characteristics. Methods: Rat type II alveolar epithelial cells were plated onto tissue culture-treated polycarbonate membrane filters. The resulting confluent monolayers on days 3 and 4 were mounted in a modified Ussing chamber and bathed on both sides with HEPES-buffered Ringer solution. The changes in short-circuit current (Isc) and monolayer resistance (R) in response to the exogenous hydroperoxide were measured. To determine the degree of cellular catalase participation in protection against $H_2O_2$ injury to the barrier, experiments were repeated in the presence of 20 mM aminotriazole (ATAZ, an inhibitor of catalase) in the same bathing fluid as the hydroperoxide. Results: These monolayers have a high transepithelial resistance (>2000 ohm-$cm^2$) and actively transport $Na^+$ from apical fluid. $H_2O_2$(0-100 mM) was then delivered to either apical or basolateral fluid. Resulting indicated that $H_2O_2$ decreased Isc and R gradually in dose-dependent manner. The effective concentration of apical $H_2O_2$ at which Isc (or R) was decreased by 50% at one hour ($ED_{50}$) was about 4 mM. However, basolateral $H_2O_2$ exposure led to $ED_{50}$ for Isc (and R) of about 0.04 mM. Inhibition of cellular catalase yielded $ED_{50}$ for Isc (and R) of about 0.4 mM when $H_2O_2$ was given apically, while $ED_{50}$ for basolateral exposure to $H_2O_2$ did not change in the presence of ATAZ. The rate of $H_2O_2$ consumption in apical and basolateral bathing fluids was the same, while cellualr catalase activity rose gradually with time in culture. Conclusion: Our data suggest that basolateral $H_2O_2$ may affect directly membrane component (e.g., $Na^+,\;K^+$-ATPase) located on the basolateral cell surface. Apical $H_2O_2$, on the other hand, may be largely degraded by catalase as it passes through the cells before reaching these membrane components. We conclude that alveolar epithelial barrier integrity as measured by Isc and R are compromised by $H_2O_2$ being relatively sensitive to basolateral (and insensitive to apical) $H_2O_2$.

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The Effect of Samul-tanggahyangbuja on Depression and Learning on Repeated Stress in Ovariectomized Rats (사물탕가향부자(四物湯加香附子)가 난소적출 흰쥐의 우울 및 학습에 미치는 영향)

  • Lee, Soon-Yee;Kim, Song-Baek;Seo, Yun-Jung;Choi, Chang-Min;Cho, Han-Baek
    • The Journal of Korean Obstetrics and Gynecology
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    • v.26 no.3
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    • pp.1-17
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    • 2013
  • Objectives: In this research, the effect of samul-tanggahyangbuja on depression and learning in ovariectomized rats subjected to repetitive stress were assessed. Samul-tanggahyangbuja is the prescription consisting of Samul-tang and Cyperi Rhizoma. Methods: Ovariectomized rats were repeatedly stressed over a 2-week period. After being orally medicated with samul-tanggahyangbuja (100 or 400 mg/kg), rats performed the Morris water maze test and forced swimming test, and social exploration was assessed in a behavior test. As well, sucrose intake was measured and measurements of blood serum corticosterone and the change of interleukin-$1{\beta}$ (IL-$1{\beta}$) and tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) in blood samples were made. Results: 1. In the Morris water maze test, rats medicated with 100 mg samul-tanggahyangbuja mastered the maze in a shorter time on the 4th day in comparison with the control group, while rats medicated with 400 mg samul-tanggahyangbuja mastered the maze more quickly (p<0.05 on the 3rd day ; p<0.01 on the 4th day, as compared to control). 2. Immobility time in the forced swimming test was significantly decreased in rats receiving 400 mg samul-tanggahyangbuja compared with the control group (p<0.05). 3. Sucrose intake and active social behavior of rats receiving 400 mg samul-tanggahyangbuja were markedly increased in comparison with the control group (p<0.01). 4. Blood serum corticosterone measurements revealed decreased blood serum corticosterone level after medicating with samul-tanggahyangbuja. But it was not statistically significant. 5. Treatment with either dose of samul-tanggahyangbuja significantly reduced IL-$1{\beta}$ and TNF-${\alpha}$ (p<0.05). Conclusions: These results suggest that samul-tanggahyangbuja possesses the anti-depressant and cognitive-enhancing activities related to menopause.

Variability in Drug Interaction According to Genetic Polymorphisms in Drug Metabolizing Enzymes

  • Jang, In-Jin;Yu, Kyung-Sang;Cho, Joo-Youn;Chung, Jae-Yong;Kim, Jung-Ryul;Lim, Hyeong-Seok;Shin, Sang-Goo
    • Environmental Mutagens and Carcinogens
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    • v.24 no.1
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    • pp.15-18
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    • 2004
  • There are significant differences in the extent of drug interactions between subjects. The influence of the genetic make up of drug metabolizing enzyme activities (CYP3A5, CYP2C19 and UDP-glucuronosyl transferase) on the pharmacokinetic drug interaction potential were studied in vivo. Nineteen healthy volunteers were grouped with regard to the $CYP3A5^{*}3$ allele, into homozygous wild-type (CYP3A5^{*}1/1^{*}1$, n=6), heterozygous $(CYP3A5^{*}1/^{*}3$, n=6), and homozygous variant-type $(CYP3A5^{*}3/^{*}3$, n=7) subject groups. The pharmacokinetic profile of intravenous midazolam was characterized before and after itraconazole administration (200 mg once daily for 4 days), and also following rifampin pretreatment (600 mg once daily for 10 days), with a washout period of 2 weeks in between. For omeprazole and moclobemide pharmacokinetic interaction study 16 healthy volunteers were recruited. The volunteer group comprised 8 extensive metabolizers and 8 poor metabolizers of CYP2C19, which was confirmed by genotyping. Subjects were randomly allocated into two sequence groups, and a single-blind, placebo-controlled, two-period crossover study was performed. In study I, a placebo was orally administered for 7 days. On the eighth morning, 300 mg of moclobemide and 40 mg of placebo were coadministered with 200 mL of water, and a pharmacokinetic study was performed. During study n, 40 mg of omeprazole was given each morning instead of placebo, and pharmacokinetic studies were performed on the first and eighth day with 300 mg of moclobemide coadministration. In the UGT study pharmacokinetics and dynamics of 2 mg intravenous lorazepam were evaluated before and after rifampin pretreatment (600 mg once daily for 10 days), with a washout period of 2 weeks in between. The subjective and objective pharmacodynamic tests were done before and 1, 2, 4, 6, 8, and 12 hrs after lorazepam administration. The pharmacokinetic profiles of midazolam and of its hydroxy metabolites did not show differences between the genotype groups under basal and induced metabolic conditions. However, during the inhibited metabolic state, the $CYP3A5^{*}3/^{*}3$ group showed a greater decrease in systemic clearance than the $CYP3A5^{*}1/^{*}1$ group $(8.5\pm3.8$ L/h/70 kg vs. $13.5\pm2.7$ L/h/70 kg, P=0.027). The 1'-hydroxymidazolam to midazolam AUC ratio was also significantly lower in the $CYP3A5^{*}3/^{*}3$,/TEX> group $(0.58\pm0.35,$ vs. $1.09\pm0.37$ for the homozygous wild-type group, P=0.026). The inhibition of moclo-bemide metabolism was significant in extensive metabolizers even after a single dose of omeprazole. After daily administration of omeprazole for 1 week, the pharmacokinetic parameters of moclobemide and its metabolites in extensive metabolizers changed to values similar to those in poor metabolizers. In poor meta-bolizers, no remarkable changes in the pharmacokinetic parameters were observed. The area under the time-effect curves of visual analog scale(VAS), choice reaction time, and continuous line tracking test results of lorazepam was reduced by 20%, 7%, 23% respectively in induced state, and in spite of large interindividual variablity, significant statistical difference was shown in VAS(repeated measures ANOVA, p=0.0027).

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Comparative Analysis of Absorption Doses between Exposed and Unexposed Area on Major Organs During CT Scan (전산화 단층촬영시 주선속내 외의 주요장기 흡수선량 비교분석)

  • 사정호;서태석;최보영;정규회
    • Progress in Medical Physics
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    • v.11 no.1
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    • pp.59-71
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    • 2000
  • It is possible to obtain a fast CT scan during breath holding with spiral technique. But the risk of radiation is increased due to detailed and repeated scans. However, the limitation of X-ray doses is not fully specified on CT, yet. Therefore, the purpose of the present study is to define the limitation of X-ray doses on CT The CT unit was somatom plus 4. Alderson Rando phantom, Solenoid water phantom, TLD, and reader were used. For determining adequate position and size of organs, the measurement of distance(${\pm}$2mm) from the midline of vertebral body was performed in 40 women(20~40 years). On the brain scan for 8:8(8mm slice thickness, 8mm/sec movement velocity of the table) and 10:10(10mm slice thickness, 10mm/sec movement velocity of the table) methods, the absorption doses of exposed area of the 10:10 were slightly higher than those of 8:8. The doses of unexposed uterus were negligible on the brain scan for both 8:8 and 10:10. On the chest scan for 8:8, 8:10(8mm slice thickness, 10mm/sec movement velocity of the table), 10:10, 10:12(10mm slice thickness, 12mm/sec movement velocity of the table) and 10:15(10mm slice thickness, 15mm/sec movement velocity of the table) methods, 8:8 method of the absorption doses of exposure area was the most highest and 10:15 method was the most lowest. The absorption doses of 8:10 method was relatively lower than those of the other methods. In conclusion, the 8:10 method is the most suitable to give a low radiation burden to patient without distorting image quality.

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Patient Position Verification and Corrective Evaluation Using Cone Beam Computed Tomography (CBCT) in Intensity.modulated Radiation Therapy (세기조절방사선치료 시 콘빔CT (CBCT)를 이용한 환자자세 검증 및 보정평가)

  • Do, Gyeong-Min;Jeong, Deok-Yang;Kim, Young-Bum
    • The Journal of Korean Society for Radiation Therapy
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    • v.21 no.2
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    • pp.83-88
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    • 2009
  • Purpose: Cone beam computed tomography (CBCT) using an on board imager (OBI) can check the movement and setup error in patient position and target volume by comparing with the image of computer simulation treatment in real.time during patient treatment. Thus, this study purposed to check the change and movement of patient position and target volume using CBCT in IMRT and calculate difference from the treatment plan, and then to correct the position using an automated match system and to test the accuracy of position correction using an electronic portal imaging device (EPID) and examine the usefulness of CBCT in IMRT and the accuracy of the automatic match system. Materials and Methods: The subjects of this study were 3 head and neck patients and 1 pelvis patient sampled from IMRT patients treated in our hospital. In order to investigate the movement of treatment position and resultant displacement of irradiated volume, we took CBCT using OBI mounted on the linear accelerator. Before each IMRT treatment, we took CBCT and checked difference from the treatment plan by coordinate by comparing it with the image of CT simulation. Then, we made correction through the automatic match system of 3D/3D match to match the treatment plan, and verified and evaluated using electronic portal imaging device. Results: When CBCT was compared with the image of CT simulation before treatment, the average difference by coordinate in the head and neck was 0.99 mm vertically, 1.14 mm longitudinally, 4.91 mm laterally, and 1.07o in the rotational direction, showing somewhat insignificant differences by part. In testing after correction, when the image from the electronic portal imaging device was compared with DRR image, it was found that correction had been made accurately with error less than 0.5 mm. Conclusion: By comparing a CBCT image before treatment with a 3D image reconstructed into a volume instead of a 2D image for the patient's setup error and change in the position of the organs and the target, we could measure and correct the change of position and target volume and treat more accurately, and could calculate and compare the errors. The results of this study show that CBCT was useful to deliver accurate treatment according to the treatment plan and to increase the reproducibility of repeated treatment, and satisfactory results were obtained. Accuracy enhanced through CBCT is highly required in IMRT, in which the shape of the target volume is complex and the change of dose distribution is radical. In addition, further research is required on the criteria for match focus by treatment site and treatment purpose.

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Antiproliferative Effect of Extracts, Fractions and Compound from Vitex rotundifolia on Human Cancer Cells (순비기 나무(Vitex rotundifolia) 추출.분획물 및 화합물의 인체 암세포 증식억제 효과)

  • Kim, You-Ah;Lee, Jung-Im;Kim, Hae-Jin;Kong, Chang-Suk;Nam, Taek-Jeong;Seo, Young-Wan
    • Journal of Applied Biological Chemistry
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    • v.52 no.4
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    • pp.180-186
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    • 2009
  • Whole plants of Vitex rotundifolia were extracted for 2 days with methylene chloride ($CH_2Cl_2$) followed by extraction of the residue for an additional 2 days. The same procedure was also applied using methanol (MeOH). The two crude extracts were combined and partitioned between $CH_2Cl_2$ and $H_2O$. The organic layer was further partitioned between n-hexane and 85% aq. MeOH, and the aqueous layer was also further fractionated with n-BuOH and $H_2O$, successively. From the 85% aq. MeOH fraction, one compound was isolated through the repeated HPLC. According to the results of physicochemical data including NMR and MS, the chemical structure of the compound was determined as artemetin (1). The antiproliferative effects of the crude extracts, fractions, and compound against HT1080, AGS, MCF-7 and HT-29 human cancer cells were compared with the control by using MTT assay. In the comparative analysis, the 85% aq. MeOH fraction exhibited the strongest antiproliferative effects on human cancer cell lines in a dose-dependent manner (p<0.05). In addition, exposure of compound 1 isolated from 85% aq. MeOH fraction led to strong antiproliferative effect in HT1080 cancer cell lines. These results suggest that the extracts and compound isolated from V. rotundifolia may be used as potential chemopreventive and chemotherapeutic agents.

Cytotoxic and Anti-inflammatory Activities of Lipids from the Nuruk (Rhizopus oryzae KSD-815) (누룩(Rhizopus oryzae KSD-815)으로부터 분리한 지질화합물의 세포독성 및 항염증 활성)

  • Kwak, Ho-Young;Lee, Sang-Jin;Lee, Dae-Young;Bae, Nark-Hyun;Jung, La-Koon;Hong, Sung-Youl;Kim, Gye-Won;Baek, Nam-In
    • Applied Biological Chemistry
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    • v.51 no.2
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    • pp.142-147
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    • 2008
  • Nuruk is the Korean traditional Koji that contains various microorganisms and has been used to make the traditional fermented foods including alcoholic beverages. Rhizopus oryzae KSD-815 was isolated from the alcohol-fermenting Nuruk used for manufacturing traditional alcohol. In this study, the authors reported the isolation and identification of four lipids from the Nuruk (Rhizopus oryzae KSD-815) that inoculated wheat with Rhizopus oryzae KSD-815. The dried and powdered Nuruk (Rhizopus oryzae KSD-815) were extracted three times at room temperature with 80% aqueous MeOH. The extracts were partitioned with EtOAc, n-BuOH, and water, successively. The EtOAc extract was suspended in 80% MeOH and partitioned repeatedly with n-hexane. From the n-hexane fraction, four lipids were isolated through the repeated silica gel and ODS column chromatographies. According to the results of physico-chemical data including NMR, GC and MS, the chemical structures of the compounds were determined as linolenic acid methyl ester (1), palmitic acid methyl ester (2), linoleic acid (3), palmitic acid (4). Cytotoxicity was evaluated in huamn breast cancer cells, MDA-MB-231 and human hepatocarcinoma, SK-HEP-1 cells using MTT assay. Exposure of compounds 1 and 3 led to a dose-dependent inhibition of cell viability in both cancer cell lines. In addition, treatment of RAW264.7 cells with compound 3 caused inhibition of lipopolysaccharide/interferon-${\gamma}$-induced nitric oxide production.

Effectiveness of the Respiratory Gating System for Stereotectic Radiosurgery of Lung Cancer (폐암 환자의 정위적 방사선 수술 시 Respiratory Gating System의 유용성에 대한 연구)

  • Song Heung-Kwon;Kwon Kyung-Tae;Park Cheol-Su;Yang Oh-Nam;Kim Min-Su;Kim Jeong-Man
    • The Journal of Korean Society for Radiation Therapy
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    • v.17 no.2
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    • pp.125-131
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    • 2005
  • Purpose : For stereotactic radiosurgery (SRS) of a tumor in the region whose movement due to respiration is significant, like Lung lower lobe, the gated therapy, which delivers radiation dose to the selected respiratory phases when tumor motion is small, was performed using the Respiratory gating system and its clinical effectiveness was evaluated. Materials and Methods : For two SRS patients with a tumor in Lung lower lobe, a marker block (infrared reflector) was attached on the abdomen. While patient' respiratory cycle was monitored with Real-time Position Management (RPM, Varian, USA), 4D CT was performed (10 phases per a cycle). Phases in which tumor motion did not change rapidly were decided as treatment phases. The treatment volume was contoured on the CT images for selected treatment phases using maximum intensity projection (MIP) method. In order to verify setup reproducibility and positional variation, 4D CT was repeated. Results : Gross tumor volume (GTV) showed maximum movement in superior-inferior direction. For patient #1, motion of GTV was reduced to 2.6 mm in treatment phases ($30{\sim}60%$), while that was 9.4 mm in full phases ($0{\sim}90%$) and for patient #2, it was reduced to 2.3 mm in treatment phases ($30{\sim}70%$), while it was 11.7 mm in full phases ($0{\sim}90%$). When comparing two sets of CT images, setup errors in all the directions were within 3 mm. Conclusion : Since tumor motion was reduced less than 5 mm, the Respiratory gating system for SRS of Lung lower lobe is useful.

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A Study of the Whitening Activities of Magnolia obovata Bark Ethyl Acetate Fractions as Cosmetic Ingredient (화장품 소재로서 후박 에틸아세테이트 분획물의 미백활성에 관한 효과)

  • Kang, Hee Cheol;Joo, Kwang Sik;Joo, Se Jin;Ha, Young Ae;Kim, Hack Soo;Cha, Mi Yeon
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.43 no.1
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    • pp.43-52
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    • 2017
  • EtOAc fractions of Magnolia obovata (M. obovata) Bark extracts were studied for the potential ingredient as a safe and effective whitening cosmetic material. The concentration of active substances honokiol was determined by HPLC. In vitro, the fractions reduced the extracellular and intracellular melanin contents in B16F10 cells in dose dependently and inhibited extracellular melanin secretion ($IC_{50}=11.05{\mu}g/mL$). The $12.5{\mu}g/mL$ treatment of maximum concentration effectively inhibited up to about 60% to the amount of extracullular melanin. Also, the $12.5{\mu}g/mL$ treatment of maximum concentration effectively inhibited up to about 59% to the amount of intracullular melanin ($IC_{50}=10.85{\mu}g/mL$). The $IC_{50}$ value of ${\alpha}-arbutin$ used as a positive control was $59.99{\mu}g/mL$. So, EtOAc fractions of M. obovata Bark extracts showed whitening effect when compared with the non-treatment group. In case of in vivo study, Cosmetic cream with EtOAc fractions of M. obovata Bark extracts was approved by Ethics committee of KDRI (IRB number: KDRI-IRB-1537). As a result in progress for skin sensitization as well as assessment of skin irritation through repeated patch test, skin allergens was identified as non sensitizing agents. Also, cosmetic cream with EtOAc fractions of M. obovata Bark extracts showed significant topical whitening effect and reliable skin safety when compared with the non-treatment group. In conclusion, EtOAc fractions of M. obovata Bark extracts may be a useful cosmetic ingredient for effective skin whitening.