• Journal of Life Science
• /
• v.31 no.10
• /
• pp.873-884
• /
• 2021

The purpose of present study is to investigate the role of artesunate (ART) in enhancing anticancer effect of nonsteroidal anti-inflammatory drug (NSAID) on human cancer cells, and we elucidate a possible molecular mechanism of this combination effect. We showed that the combined effect of ART with NSAID such as celecoxib (CCB) or dimethyl-CCB (DMC) in various type of human cancer cells. After ART treatment, the expression of p62, nuclear factor erythroid 2-like 2 (NRF2) and cancer stemness (CS)-related proteins including CD44, CD133, aldehyde dehydrogenase 1 (ALDH1), octamer-binding transcription factor 4 (Oct4), mutated p53 (mutp53) and c-Myc was down-regulated. ART induced autophagy as reduction of the autophagy receptor p62, which was associated with up-regulation of activating transcription factor 4 (ATF4) and C/EBP homologous protein (CHOP), and simultaneous down-regulation of NRF2 and CS-related proteins was occurred in the human cancer cells. These results indicate a possibility that ART activates autophagy through ATF4-CHOP cascade leading to down-regulation of CS-related proteins and subsequently eradicated cancer stem cells. In addition, co-treatment with ART and imatinib was more effective than either drug alone on growth inhibition and apoptosis induction of cancer cells. In conclusion, induction of autophagy-dependent cell death by ART might play a critical role in mediating the synergistic effect of drug combination (ART/NSAID and ART/imatinib). Therefore, ART could be a promising candidate as a chemosensitizer to enhance the anticancer effects of NSAID and imatinib.

• Journal of the Korean Society of Food Science and Nutrition
• /
• v.40 no.8
• /
• pp.1099-1106
• /
• 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.

• Korean Journal of Medicinal Crop Science
• /
• v.13 no.6
• /
• pp.261-267
• /
• 2005

Alcohol metabolizing and antioxidant activity of Mentha species were investigated in rat liver. Fifty six Sprague Dawley rats were randomly divided into seven groups such as normal (ethanol excluded), negative control (40% ethanol (10 g/kg of body weight/day) fed), positive control (1 g Silymarin/kg of body weight/day with ethanol fed), two Mentha viridis extracts (0.2 g & 1 g M. viridis methanol ext./kg of body weight/day with ethanol fed) and two M piperita extracts (0.2 g & 1 g M. piperita methanol ext./kg of body weight/day with ethanol fed) groups. After 2 weeks, rats were sacrificed under ether. The activities of alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH), catalase (CAT), manganese superoxide dismutase (Mn-SOD), glutathione peroxidase (GAH-px) and the content ofthiobarbituric acid reactive substance (TBARS) in the rat livers and the activity of glutamate pyruvate transferase (GPT) in serum were evaluated. From the analyses, 1 g M. viridis and 0.2 g M. piperita administrated groups showed higher ADH and ALDH activity than the other groups. Groups fed with 0.2 g and 1 g M. viridis ext. and 0.2 g M. piperita ext. showed higher CAT activity than the other groups. All the Mentha extract fed groups exhibited more effective in recovering Mn-SOD, GSH-px and GPT acitivities to a similar degree of normal group. TBARS contents of two M. viridis ext. fed group and 0.2 g M. piperita ext. fed group were higher than those of the other groups. M. viridis extract fed groups showed more effective in CAT and Mn-SOD activities than M. piperita extract groups at p < 0.05. Finally, it is concluded that both Mentha species have alcohol metabolizing and antioxidant activity and M viridis is more effective than M. piperita.

• Journal of the Korean Society of Food Science and Nutrition
• /
• v.41 no.7
• /
• pp.927-935
• /
• 2012

This study was performed to develop functional vinegar by using cucumbers through two stages of fermentation. The alcohol content was maximized (7.8%) after 6-days of alcohol fermentation at $25^{\circ}C$ by adjusting the initial sugar concentration to $15^{\circ}Brix$, and vinegar with an acidity of 5.8% was obtained after 12-days of acetic acid fermentation at $30^{\circ}C$. The major sugars in the produced vinegar were glucose and fructose, which were present in concentrations of 3,067.26 and 395.73 mg%, respectively. The major organic acids were acetic acid and succinic acid, which were present in concentrations of 4,410.5 and 841.11 mg%, respectively. The total free amino acid content of the cucumber vinegar was 181.45 ${\mu}g/mL$ and citrulline, valine, aspartic acid, asparagine, and ornithine were the major amino acids. The inorganic components included various alkaline elements, such as K, Ca, and Mg. In addition, experimental methods to assess the DPPH and $ABTS^+$ radical-scavenging ability, reducing power, and ${\beta}$-carotene bleaching activity showed that the cucumber vinegar had strong antioxidant properties. The total polyphenol content, which are the major components responsible for the antioxidant activities of the cucumber vinegar, was 40.14 mg/100 mL. The cucumber vinegar showed significantly higher hepatic aldehyde dehydrogenase activity when compared to the alcoholic control (negative) and the marketing drink (positive), resulting in decreased plasma acetaldehyde concentrations in rats. These results demonstrate that cucumber vinegar possesses antioxidant properties and holds great promise for use in preventing hangovers.

• Proceedings of the Korean Society of Applied Pharmacology
• /
• 1995.04a
• /
• pp.91-91
• /
• 1995

에탄올에 의한 급성독성은 에탄올, 아세트알데히드 및 에탄을 대사산물의 변형생성물질 등에 기인하므로 알콜 섭취 후 혈중 에탄을 농도 및 아세트알데히드의 농도를 낮추는 것은 음주에 의한 급성 중독상태에 머무는 시간을 단축시키는데 중요하다. 본 실험에서는 Bacillus subtilis natto sp.를 식물 추출액을 배지로 하여 배양한 후 단백 분해효소로 고분자물질을 절단하여 얻은 발효액인 바이오짐(상품명: Biozyme)을 주성분으로 한 '비지니스(조선무약합자회사)' 의 인체 혈중 알콜대사 촉진작용을 검색하였으며, 비지니스 및 바이오짐이 랫드의 에탄을 대사에 미치는 효과를 검토하여 다음과 같은 결과를 얻었다. 인체 혈중 알콜대사 촉진작용을 검색하기 위해 알콜 섭취 전과 후의 혈중 에탄올 농도를 비교하였는데, 대조군에 비해 비지니스 투여군이 30분 후부터 2시간 후까지 혈청 알콜농도가 낮게 나타났다. 대조군의 혈청 알콜농도를 100으로 하였을 때 알콜 투여 30분, 60분, 90분, 120분 경과 후 시험군은 각각 대조군의 84.3%, 89,0%, 85.9%, 75.8%를 나타내어 평균 16% 정도 낮았다. 시험군의 AUC는 대조군의 AUC의 89%로 비지니스 투여군에서 혈액내 알콜의 제거가 빠르게 진전된다는 것을 보여주었다. 또한, 랫드의 에탄을 대사에 미치는 효과를 알아보고자 바이오짐 및 비지니스 투여 후 채혈하여 혈중 에탄을 및 아세트알데히드 농도를 측정하였다. 비즈니스 투여시 혈중 알콜 농도는 알콜 투여 60분 경과후 가장 큰 감소 효과(대조군:83.70$\pm$11.80mg/이, 시험군:45.12$\pm$6.63mg/d1, 47% 감소)를 나타내었으며, 시험군의 AUC는 대조군에 비해 30% 감소하였다. 혈중 아세트알데히드 농도는 투여 60분 후 비지니스 투여군(4.56$\pm$0.51nmol/$m\ell$)이 대조군(6.45$\pm$0.64nmo1/$m\ell$)에 비해 유의성 있는 감소(29%)를 나타내었으며, 시험군의 AUC는 대조군에 비해 35% 감소하였다. 바이오짐 투여시 혈중 에탄을 농도가 알콜 투여 2시간 경과 후 가장 큰 감소 효과(대조군:49.10$\pm$5.20mg/dl, 시험군:25.90$\pm$7.16mg/d1, 47% 감소)를 나타내었으며, 시험군의 AUC는 대조군에 비해 39% 감소하였고, 혈중 아세트알데히드의 농도는 투여 60분후 시험군(3.96$\pm$0.07nmo1/$m\ell$)이 대조군(6.45$\pm$0,64nmo1/$m\ell$)에 비해 유의성 있는 감소(39%)를 나타내었으며, 시험군의 AUC는 대조군에 비해 48% 감소하였다 한편, 시험관내 에탄올 대사 효소에 대한 바이오짐의 효과를 검색해본 결과 바이오짐(2.0 $\mu\textrm{g}$/assay)에 의해 Aldehyde dehydrogenase(1.5unit/assay)의 활성이 14% 증가되었다. 본 연구의 결과로 볼 때, 비지니스 및 바이오짐은 음주 후 상승된 혈중 에탄을 농도 및 아세트알데히드의 농도를 현저히 감소시키는 효과가 있었다.