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Comparison of Anti-inflammatory Activities among Ethanol Extracts of Sophora flavescens, Glycyrrhiza uralensis and Dictamnus dasycarpus, and their Mixtures in RAW 246.7 Murine Macrophages (RAW 246.7 대식세포 모델에서 고삼, 감초, 백선피 에탄올 추출물 및 추출복합물의 항염증 효능 비교)

  • Han, Min Ho;Lee, Moon Hee;Hong, Su Hyun;Choi, Yung Hyun;Moon, Ju Sung;Song, Myung Kyu;Kim, Min Ju;Shin, Su Jin;Hwang, Hye Jin
    • Journal of Life Science
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    • v.24 no.3
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    • pp.329-335
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    • 2014
  • Sophora flavescens, Glycyrrhiza uralensis and Dictamnus dasycarpus have been widely used in folk medicine for several inflammatory disorders in Korea and China. In this study, we compared the anti-inflammatory effects of the ethanol extracts of S. flavescens (EESF), G. uralensis (EEGU) and D. dasycarpus (EEDS), and their mixtures (medicinal herber mixtures, MHMIXs) on production of inflammatory mediators and cytokines in lipopolysaccharide (LPS)-stimulated RAW 264.7 murine macrophages. Our data indicated that treatment with EESF, EEGU and EEDD significantly inhibited the excessive production of pro-inflammatory mediators such as nitric oxide (NO) and prostaglandin $E_2$ ($PGE_2$) in LPS-stimulated RAW 264.7 cells. The ethanol extracts and MHMIXs also attenuated the production of pro-inflammatory cytokines, including interleukin-$1{\beta}$ ($IL-1{\beta}$) and tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$) by suppressing their protein expression, respectively. Interestingly, MHMIX-1, which basic ingredients are EESF, EEGU and EEDS in the proportion 3:1:1, more safely and effectively inhibits the LPS-induced inflammatory status in LPS-stimulated RAW 264.7 macrophages compared to ethanol extracts of each medicinal herb and other MHMIXs without causing any cytotoxic effects. Our study provides scientific evidence to support that a berbal mixture, MHMIX-1 may be useful in the treatment of inflammatory diseases by inhibiting inflammatory regulator responses in activated macrophages.

Inhibitory Effects of Tenebrio molitor Larvae Ethanol Extract on RANKL-Induced Osteoclast Differentiation (갈색거저리 유충 에탄올 추출물이 RANKL에 의해 유도되는 파골세포 분화에 미치는 영향)

  • Seo, Minchul;Baek, Minhee;Lee, Hwa Jeong;Shin, Yong Pyo;Lee, Joon Ha;Kim, In-Woo;Kim, Mi-Ae;Hwang, Jae-Sam
    • Journal of Life Science
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    • v.30 no.11
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    • pp.983-989
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    • 2020
  • The balance between bone-resorbing osteoclasts and bone-forming osteoblasts is key to bone health. An imbalance between osteoclasts and osteoblasts leads to various bone-related disorders, such as osteoporosis, osteomalacia, and osteopetrosis. However, the bone-resorption inhibitor drugs that are currently used may cause side effects. Natural substances have recently received much attention as therapeutic drugs for the treatment of bone health. This study was designed to determine the effect of Tenebrio molitor larvae ethanol extract (TME) on receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation. To measure the effect of TME on osteoclast differentiation, RAW264.7 cells were treated with RANKL with or without TME for 5 days. The tartrate-resistant acid phosphatase (TRAP) activity was significantly inhibited by treatment of TME without cytotoxicity up to 2 mg/ml. In addition, TME effectively suppressed expression of osteoclast differentiation-related marker genes and proteins such as TRAP, NFATc1, and c-Src. TME also significantly inhibited the p38 mitogen-activated protein kinase (MAPK) signaling pathway without affecting ERK and JNK signaling in RANKL-induced RAW264.7 cells. Consequently, we conclude that TME suppresses osteoclast differentiation by inhibiting RANKL-induced osteoclastogenic genes expression through the p38 MAPK signaling pathways. These results suggest that TME and its bioactive components are potential therapeutics for bone-related diseases such as osteoporosis.

Studies on Seed Germination Characters and Germination Inhibitors of Bupleurum falcatum L. (자호(紫胡)의 발아특성(發芽特性)과 발아억제물질(發芽抑制物質)에 관(關)한 연구(硏究))

  • Lee, Sang-Hyun;Lee, Sang-Chul
    • Korean Journal of Medicinal Crop Science
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    • v.5 no.4
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    • pp.276-283
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    • 1997
  • This experiment was conducted to investigate the optimum temperature and the effects of sulfuric acid, flowing water and $GA_3$ on the germination of Bupleurum falcatum. At the same time, the effect of germination-related compounds in Bupleurum falcatum seed was tested. Among the tested temperatures $(15,\;20,\;25\;and\;30^{\circ}C)$ the highest germination rate was obtained at $15^{\circ}C$. The optimum soaking time of sulfuric acid was 5 minutes at the concentration of both 0.1 and 1.0%. At the same time, the germination rate was highest when Bupleurum falcatum seed was washed for 2 days in the flowing water before germination test. The effect of $GA_3$ on the germination was highest at 100 ppm out of 10, 50 and 100 ppm. Regardless of treatments, the germination rate of Jeongseon species was higher than that of Mishima species. SEM photographs revealed that most of germination-inhibiting substances in the seed coat were washed away by rinsing in the flowing water for 2 days thus the seed coat became more smooth. The 4, 000 ppm alcohol extract of Bupleurum falcatum seeds inhibited the germination of lettuce seeds as much as 41.7% in Jeongseon species and 58.3% in Mishima species. The higher extract concentration from seed of Bupleurum falcatum, the lower the germination of lettuce seeds was obtained. Out of phenolic acids, the contents of orchinol, pyrogallol, and p-hydroxybenzoic acid were highest in both varieties. Compared with Mishima species, Jeongseon species showed much higher content of salicylic and vanillic acid.

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The Effect of Sahyangsohapwon on Heart Rate Variability of Healthy Subjects (사향소합원(麝香蘇合元)이 정상인의 심박변이도에 미치는 영향)

  • Kim, Chang-Hyun;Hwang, Jae-Woong;Min, In-Kyu;Kim, Mi-Young;Byeon, Hyung-Sik;Na, Byong-Jo;Park, Sung-Wook;Park, Jung-Mi;Ko, Chang-Nam;Bae, Hyung-Sup;Jung, Woo-Sang;Moon, Sang-Kwan;Cho, Ki-Ho;Kim, Young-Suk
    • The Journal of Korean Medicine
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    • v.30 no.1
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    • pp.120-127
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    • 2009
  • Objectives: Sahyangsohapwon (SS) is a herbal medication that has been widely used with circulatory and neural diseases. This study was conducted to assess the effect of SS on the autonomic nervous system by using heart rate variability measurement. Methods: The eligible subjects were enrolled from the healthy male group of ages 20 to 35 years. They were divided into two groups, the SS group (n=26) and the control (n=24). We monitored the ECG of subjects from the time period 14:00 to 18:00. In the SS group, subjects were administered with a dose of SS at the time 15:00, whereas the control group had none. For each hour HRV measurement was monitored every 15 minutes for 512 seconds from the time period 14:00 to 18:00. The mean value, which was calculated using the 4 values during each hour (i.e. 14:00, 14:15, 14:30, 14:45), was used as the representative value for each individual hour. For the measurement values, RR-interval and SDNN (standard deviation of the NN intervals) were used as time domain analysis, and HF (high frequency), LF (low frequency), and LF/HF ratio were used as frequency domain analysis. Results: The LF value showed an increase after one hour of SS administration and showed gradual diminution for each and every hour. The repeated measures of ANOVA for the comparison of the LF value between the SS group and the control group showed significant differences. While, RR interval, SDNN, HF, and LF/HF ratio values showed no significant differences between the two groups. Conclusions: We suggest that the SS might be useful for stabilizing autonomic nervous system by inhibiting sympathetic nerve activation in healthy people.

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Development of Liquid Cadmium Cathode Structure for the Inhibition of Uranium Dendrite Growth (수지상 우라늄 성장억제를 위한 액체카드뮴 음극구조 개발)

  • Paek, Seung-Woo;Yoon, Dal-Seong;Kim, Si-Hyung;Shim, Jun-Bo;Ahn, Do-Hee
    • Journal of Nuclear Fuel Cycle and Waste Technology(JNFCWT)
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    • v.8 no.1
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    • pp.9-17
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    • 2010
  • The LCC (Liquid Cadmium Cathode) structure to be developed for inhibiting the formation and growth of the uranium dendrite has been known as a key part in the electrowinning process for the simultaneous recovering of uranium and TRU (TRans Uranium) elements from spent fuels. A zinc-gallium (Zn-Ga) experimental system which is able to be functional in aqueous condition and normal temperature has been set up to observe the formation and growth phenomena of the metal dendrites on liquid cathode. The growth of the zinc dendrites on the gallium cathode and the performance of the existing stirrer type and pounder type cathode structure were observed. Although the mechanical strength of the dendrites appeared to be weak in the electrolyte and easily crashed by the various cathode structures, it was difficult to effectively submerge the dendrite into the bottom of the liquid cathode. Based on the results of the aqueous phase experiments, a lab-scale electrowinning experimental apparatus which are applicable to the development of LCC srtucture for the electrowinning process was established and the performance tests of the different types of LCC structure were conducted to prohibit the uranium dendrite growth on LCC surface. The experimental results of the stirrer type LCC structures have shown that they could not effectively remove the uranium dendrites growing at the inner side of the LCC crucible and the performances of the paddle and harrow type LCC structure were similar. Therefore a mesh type LCC structure was developed to push down the uranium dendrites to the bottom of the LCC crucible growing on the LCC surface and at the inner side of the crucible. From the experimental results for the performance test of the mesh type LCC structure, the uranium was recovered over 5 wt% in cadmium without the growth of uranium dendrites. After completion of the experiments, solid precipitates of the bottom of the LCC crucible were identified as an intermetallic compound (UCd11) by the chemical analysis.

Synergistic effect of ionizing radiation and $\beta$-lapachone against tumor in vitro and in vivo

  • Park, Eun-Kyung;Kim, Young-Seok;Lee, Sang-wook;Ahn, Seung-Do;Shin, Seong-Soo;Park, Heon-Joo;Song, Chang-Won
    • Proceedings of the Korean Biophysical Society Conference
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    • 2003.06a
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    • pp.80-80
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    • 2003
  • ${\beta}$-lapachone(${\beta}$-Lap), a natural o-naphthoquinone, presents in the bark of the Lapacho tree. ${\beta}$-Lap is cytotoxic against a variety of human cancer cells and it potentiates the anti-tumor effect of Taxol. In addition, ${\beta}$-Lap has been reported to radiosensitize cancer cells by inhibiting the repair of radiation-induced DNA damage.In the present study, we investigated the cytotoxicity of ${\beta}$-Lap against RKO human colorectal cancer cells as well as the combined effect of ${\beta}$-LaP and ionizing radiation. An incubation of RKO cells with 5 ${\mu}$M of ${\beta}$-Lap for 4 h killed almost 90% of the clonogenic cells. An incubation of RKO cells with 5 ${\mu}$M of ${\beta}$-Lap for 4 h or longer also caused massive apoptosis. Unlike other cytotoxic agents, ${\beta}$-Lap did not increase the expression of p53 and p21 and it suppressed the NFkB expression. The expression of Caspase 9 and 3 was minimally altered by ${\beta}$-Lap. Radiation and ${\beta}$-Lap acted synergistically in inducing clonogenic cell death and apoptosis in RKO cells when ${\beta}$-Lap treatment was applied after but not before the radiation exposure of the cells. Interestingly, a 4 h treatment with 5 ${\mu}$M of ${\beta}$-Lap starting 5 h after irradiation was as effective as that starting immediately after irradiation. The mechanisms of ${\beta}$-Lap-induced cell killing is controversial but a recent hypothesis is that ${\beta}$-Lap is activated by NAD(P)H: quinone-onidoreductase (NQO1) in the cells followed by an elevation of cytosolic Ca$\^$2+/ level and activation of proteases leading to apoptosis. It has been reported that NQO1 level in cells is markedly up-regulated for longer than 10 h after irradiation. Indeed, using immunological staining of NQO1, we observed a significant elevation of NQO1 expression in RKO cells 5h after 2-4 Gy irradiation. Such a prolonged elevation of NQO1 level after irradiation may be the reasons why the ${\beta}$-Lap treatment applied S h after irradiation was as effective as that applied immediately after irradiation in killing the cells. In view of the fact that the repair of radiation-induced damage is usually completed within 1-2 h after irradiation, it is highly likely that the ${\beta}$-Lap treahment applied 5 h after irradiation could not inhibit the repair of radiation-induced damage. For in vivo study, RKO cells were injected S.C. into the hind-leg of Nu/Nu mice, and allowed to grow to 130 mm3 tumor. The mice were i.p. injected with ${\beta}$-lapachone or saline 2 h after irradiation of tumors with 10 Gy of X-rays. The radiation induced growth delay was increased by 2.4 $\mu\textrm{g}$/g of ${\beta}$-lapachone. Taken together, we may conclude that the synergistic interaction of radiation and ${\beta}$-Lap in killing cancer cells is not due to radiosensitization by ${\beta}$-Lap but to an enhancement of ${\beta}$-Lap cytotoxicity by radiation through an upregulation of NQO1. The fact that NQO1 is elevated in tumors and that radiation causes prolonged increase of the NQO1 expression may be exploited to preferentially kill tumor cells using ${\beta}$-Lap in combination with radiotherapy.

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Quality Preservation of Shredded Carrots Stored in UV LED Packaging System (자외선 LED 포장용기 시스템에 의한 포장절단당근의 품질보존)

  • Kim, Nam Yong;Lee, Dong Sun;An, Duck Soon
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.43 no.1
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    • pp.135-140
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    • 2014
  • Pre-storage ultra-violet (UV) light treatment on fresh produce is known to inactivate the contaminated microorganisms, activate the defense system, and delay ripening extending the shelf life. As UV light emitting diode (LED) becomes available at a relatively low price, continuous or intermittent UV treatment during chilled storage is possible in a container or package. This study attempted an in situ UV LED treatment on fresh produce stored under a refrigerated container in order to see its potential in the fresh produce storage and further optimize its application conditions. The effect of in-container UV LED irradiation on the quality preservation of shredded carrots was investigated in the air and modified atmosphere (MA) conditions. Two sets of experiment with Escherichia coli inoculation and with natural microbial flora in the air (two 30 minute on-off cycles of 1 $diode/dm^2$ per day at a location above 2 cm) showed a clear and significant effect of the UV LED irradiation on the suppression of microbial growth: 280 nm was the most effective by maintaining a lower microbial count by at least 0.5 log (CFU/g) throughout the 6 day storage period. The carotenoids content of shredded carrots subjected to UV LED treatment at 365 and 405 nm in the air was higher than that of the control shredded carrots. In MA condition of $O_2$ of 1.2~4.3% and $CO_2$ of 8.4~10.6% being indifferent with LED wavelengths, 280 nm UV LED irradiation was also effective in inhibiting the microbial growth. While there was no observed difference in the carotenoids content between untreated and UV LED-treated shredded carrots in MA, UV LED irradiation at 365 and 405 nm was slightly better in DPPH radical scavenging activity. The use of UV LED in storage container or package seems to give the benefits of preserving the microbial and nutritional qualities of minimally processed fruits and vegetables.

The Immunohistochemical Analysis for the Expression of Survivin, an Inhibitor of Apoptosis Protein, in Non-small Cell Lung Cancer (비소세포폐암에서 아포프토시스 억제 단백질 Survivin 발현에 관한 면역조직학적 분석)

  • Ko, Mi-Hye;Myoung, Na-Hye;Lee, Jae-Whan;Cho, Eun-Mi;Park, Jae-Seuk;Kim, Keun-Youl;Lee, Kye-Young
    • Tuberculosis and Respiratory Diseases
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    • v.48 no.6
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    • pp.909-921
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    • 2000
  • Background : Defects in apoptotic signaling pathways play important role in tumor initiation, progression, metastasis and resistance to treatment. Several proteins which may promote tumorigenesis by inhibiting apoptosis were identified. The survivin protein is the member of inhibitor of apoptosis protein(IAPs) family which inhibits apoptosis. Unlike other IAPs, it is expressed in during the fetal period but not in adult differentiated tissues. Many reports have stated that survivin is selectively expressed in many cancer cell lines and cancer tissues. We performed immunohistochemical analysis for survivin expression in non-mall cell lung cancer to get evaluate its clinical implication. Methods : Twenty nine surgically resected lung cancers were examined. Immunohistochemical staining were performed by immuno-peroxidase technique using avidin-biotinylated horseradish pemxidase complex in the formalin-fixed, paraffin-embedded tissue $4{\mu}m$ section. Anti-survivin polyclonal antibody was used for primary antibody and anti-p53 monoclonal antibody was also used to analyze the correlation between survivin and p53 expression. The survivin expression scores were determined by as the sum of the stained area and intensity. Results : Immunohistochemical analysis showed cancer specific expression of survivin in 20 of 29 cases (69.0%). Western blot analysis also showed the selective survivin expression in tumor tissue. There was no correlation between survivin expression and clinicopathological parameters and prognosis. We analyzed the ∞π'elation between survivin expression and p53 expression, but found none. Conclusion: We confirmed the tumor specific expression of survival in non-small cell lung canær. But this expression was not correlated with clinical parameters as well as histology, tumor stage, recurrence, and survival rate. Also it was not statistically correlated with the expression of p53.

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IP-10 Decreases TNF-α Induced MUC5AC Expression in Human Airway Epithelial Cells: a Possible Relation with Little Sputum Production in Idiopathic Pulmonary Fibrosis (IP-10에 의한 기도상피세포에서의 TNF-α 유도 MUC5AC발현 억제: 특발성폐섬유증 환자의 적은 객담과의 연관성)

  • Kim, Seung Joon;Kang, Chun Mi;You, Moon Bin;Yoon, Hyung Kyu;Kim, Young Kyoon;Kim, Kwan Hyoung;Moon, Hwa Sik;Park, Sung Hak;Song, Jeong Sup
    • Tuberculosis and Respiratory Diseases
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    • v.64 no.5
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    • pp.347-355
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    • 2008
  • Background: IPF is characterized by chronic, fibrosing inflammatory lung disease of unknown etiology. Typical symptoms of IPF are exertional dyspnea with nonproductive cough. Why patients with typical IPF have dry cough rather than productive cough, is unknown. IP-10 plays an important regulatory role in leukocyte trafficking into the lung. The present study investigated the effect of IP-10 in the pathogenesis of dry cough rather than productive cough in IPF patients. Methods: IP-10 concentration was measured by ELISA from BALF of IPF patients. To evaluate the role of IP-10 in mucin expression, the expression of the MUC5AC mucin gene was measured in NCI-H292 cells, a human pulmonary mucoepidermoid carcinoma cell line, after stimulation by TNF-${\alpha}$ with or without IP-10 pretreatment. EGFR-MAPK expression was also examined as a possible mechanism. Results: IP-10 levels were significantly higher in the BALF of IPF patients compared to healthy controls. IP-10 pretreatment reduced TNF-${\alpha}$ induced MUC5AC mucin expression by inhibiting the EGFR-MAPK signal transduction pathway in NCI-H292 cells. Conclusion: These findings suggest that little mucus production in IPF patients might be attributable to IP-10 overproduction, which inhibits the EGFR-MAPK signal transduction pathway required for MUC5AC mucin gene expression.

Effect of Fermented Cucumber Beverage on Ethanol Metabolism and Antioxidant Activity in Ethanol-treated Rats (오이 발효음료가 만성적으로 에탄올을 급여한 흰쥐의 에탄올 대사와 항산화방어계에 미치는 영향)

  • Lee, Hae-In;Seo, Kwon-Il;Lee, Jin;Lee, Jeom-Sook;Hong, Sung-Min;Lee, Ju-Hye;Kim, Myung-Joo;Lee, Mi-Kyung
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.40 no.8
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    • pp.1099-1106
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    • 2011
  • Cucumber fermentation has been used as a means of preservation. This study was performed to investigate the effects of fermented cucumber beverage (CF) containing beneficial materials for an ethanol hangover based on Hovenia dulcis (SKM) on ethanol-induced hepatotoxicity. Male Sprague-Dawley rats were randomly divided into three groups: ethanol control, ethanol plus SKM, and ethanol plus CF+SKM. SKM or CF+SKM was orally administered at a dose of 7 mL/kg body weight once per day for 5 weeks. Control rats were given an equal amount of water. CF+SKM significantly lowered plasma ethanol levels, whereas SKM tended to decrease the levels compared to the control. Both SKM and CF+SKM significantly lowered the plasma acetaldehyde levels and serum transaminase activities compared to those in the control. SKM and CF+SKM did not affect hepatic alcohol dehydrogenase activity; however, it significantly inhibited cytochrome P450 2E1 (CYP2E1) activity. Hepatic aldehyde dehydrogenase (ALDH) activity was significantly higher in the SKM and CF+SKM groups than that in the control group. Plasma acetaldehyde concentration was significantly correlated with hepatic CYP2E1 (r=0.566, p<0.01) activity and ALDH (r=-0.564, p<0.01) activity. Hepatic superoxide dismutase and catalase activities as well as glutathione content increased with the SKM and CF+SKM administration, whereas lipid peroxide content decreased significantly. Furthermore, SKM and CF+SKM lowered plasma and hepatic lipid content and lipid droplets compared to those in the control group. These results indicate that SKM and CF+SKM exhibit hepatoprotective properties partly by inhibiting CYP2E1 activity, enhancing ALDH activity and stimulating the antioxidant defense systems in ethanol-treated rats.