• Title/Summary/Keyword: Mechanism of action

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Inhibition of Production of Reactive Oxygen Species and Gene Expression Profiles by Cirsii Japonici Herba Extract Treatment in HepG2 Cells

  • Rho, Sam-Woong;Chung, Hwan-Suck;Kang, Moon-Kyu;Na, Young-In;Cho, Chong-Woon;Kim, Hyung-Min;Jung, Hyuk-Sang;Park, Hi-Joon;Kim, Hong-Yeoul;Hong, Moo-Chang;Shin, Min-Kyu;Kim, Sung-Soo;Bae, Hyun-Su
    • Molecular & Cellular Toxicology
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    • v.1 no.4
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    • pp.224-229
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    • 2005
  • Cirsii Japonici Herba (CJH) extract has been used for hundreds of years in Asian countries as a treatment for pollutant, radiation, and alcohol-induced liver damage. The reducing effect of CJH on hydrogen peroxide-induced reactive oxygen species (ROS) production, the main cause of cell damage or death, was evaluated using the HepG2 cell line. Cell survival was determined using MTS assay. The viability of cells treated with CJH was not significantly different from oxidative-stressed HepG2 cells. A dose-dependent inhibitory effect by CJH on ROS production was shown in oxidative-stressed cells using the $H_{2}DCFDA$ assay. To identify candidate genes responsible for the anti-oxidative effects of CJH on HepG2 cells, an oligonucleotide microarray analysis was performed. The expressions of five genes were decreased, whereas nineteen genes were up-regulated in CJH plus hydrogen peroxide treated cells, compared to only hydrogen peroxide treated cells. Among them, the expression of 5 genes was decreased in hydrogen peroxide treatment when compared to control. These genes are known to regulate cell survival and progression. On the other hand, it was shown that its main compounds were not a sylimarin or its analogs. The list of differentially expressed genes may provide further insight on the action and mechanism behind the anti-oxidative effects of Cirsii Japonici Herba.

Black ginseng-enriched Chong-Myung-Tang extracts improve spatial learning behavior in rats and elicit anti-inflammatory effects in vitro

  • Saba, Evelyn;Jeong, Da-Hye;Roh, Seong-Soo;Kim, Seung-Hyung;Kim, Sung-Dae;Kim, Hyun-Kyoung;Rhee, Man-Hee
    • Journal of Ginseng Research
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    • v.41 no.2
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    • pp.151-158
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    • 2017
  • Background: Chong-Myung-Tang (CMT) extract is widely used in Korea as a traditional herbal tonic for increasing memory capacity in high-school students and also for numerous body ailments since centuries. The use of CMT to improve the learning capacity has been attributed to various plant constituents, especially black ginseng, in it. Therefore, in this study, we have first investigated whether black ginseng-enriched CMT extracts affected spatial learning using the Morris water maze (MWM) test. Their molecular mechanism of action underlying improvement of learning and memory was examined in vitro. Methods: We used two types of black ginseng-enriched CMT extracts, designated as CM-1 and CM-2, and evaluated their efficacy in the MWM test for spatial learning behavior and their anti-inflammatory effects in BV2 microglial cells. Results: Our results show that both black ginseng-enriched CMT extracts improved the learning behavior in scopolamine-induced impairment in the water maze test. Moreover, these extracts also inhibited nitric oxide production in BV2 cells, with significant suppression of expression of proinflammatory cytokines, especially inducible nitric oxide synthase, cyclooxygenase-2, and $interleukin-1{\beta}$. The protein expression of mitogen-activated protein kinase and nuclear $factor-{\kappa}B$ pathway factors was also diminished by black ginseng-enriched CMT extracts, indicating that it not only improves the memory impairment, but also acts a potent anti-inflammatory agent for neuroinflammatory diseases. Conclusion: Our research for the first time provides the scientific evidence that consumption of black ginseng-enriched CMT extract as a brain tonic improves memory impairment. Thus, our study results can be taken as a reference for future neurobehavioral studies.

Inhibitory Effects of Extracts from Albizzia julibrissin on Gonadal Maturation in a Medaka (Oryzias latipes) (자귀나무 추출물이 송사리(Oryzias latipes) 생식소 성숙에 대한 억제효과)

  • Lee, Eun-Hee;Oh, Sang-Pil;Kim, Myong-Hee;Kim, Kwang-Hyun;Hong, Sang-Hoon;Han, Chang-Hee
    • Journal of Life Science
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    • v.23 no.3
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    • pp.333-340
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    • 2013
  • This study was performed to determine whether stem bark extract containing saponin of Albizzia julibrissin in the diet influences gonadal maturation and spawning in medaka (Oryzias latipes). The crude extraction containing saponin (HaBC) was partially purified from n-BuOH extraction of A. julibrissin stem bark by Diaion HP-20, Silica gel and Sephadex LH-20 chromatographies. We fed diets supplemented with HaBC to medaka. We then studied the effects of the HaBC supplement on the suppression of gonadal maturation and spawning in female medaka that were reared in aquaria with recirculation systems. In the experiment with immature female medaka, the periods of initiation of gonadal maturation and spawning were delayed in the fish that were fed diets supplemented with at least HaBC 20 mg/g-feed. In the experiment with mature female medaka, the fish that were fed diets supplemented with at least HaBC 20 mg/g-feed had lower GSIs than the control diet group did. The results showed that the growth of the immature medaka was not correlated with the amount of supplementation of HaBC in the diet. However, the condition factors (CF) in the medaka that were fed diets supplemented with at least HaBC 20 mg/g-feed were higher than in the medaka fed on the control diet. We concluded that extracts containing saponin from the stem bark of A. julibrissin have the potential to inhibit gonadal maturation in female medaka, but they did not act as growth stimulation. Further studies are required to determine the mechanism of the action.

Epigallocatechin-3-gallate suppresses hemin-aggravated colon carcinogenesis through Nrf2-inhibited mitochondrial reactive oxygen species accumulation

  • Seok, Ju Hyung;Kim, Dae Hyun;Kim, Hye Jih;Jo, Hang Hyo;Kim, Eun Young;Jeong, Jae-Hwang;Park, Young Seok;Lee, Sang Hun;Kim, Dae Joong;Nam, Sang Yoon;Lee, Beom Jun;Lee, Hyun Jik
    • Journal of Veterinary Science
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    • v.23 no.5
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    • pp.74.1-74.16
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    • 2022
  • Background: Previous studies have presented evidence to support the significant association between red meat intake and colon cancer, suggesting that heme iron plays a key role in colon carcinogenesis. Epigallocatechin-3-gallate (EGCG), the major constituent of green tea, exhibits anti-oxidative and anti-cancer effects. However, the effect of EGCG on red meat-associated colon carcinogenesis is not well understood. Objectives: We aimed to investigate the regulatory effects of hemin and EGCG on colon carcinogenesis and the underlying mechanism of action. Methods: Hemin and EGCG were treated in Caco2 cells to perform the water-soluble tetrazolium salt-1 assay, lactate dehydrogenase release assay, reactive oxygen species (ROS) detection assay, real-time quantitative polymerase chain reaction and western blot. We investigated the regulatory effects of hemin and EGCG on an azoxymethane (AOM) and dextran sodium sulfate (DSS)-induced colon carcinogenesis mouse model. Results: In Caco2 cells, hemin increased cell proliferation and the expression of cell cycle regulatory proteins, and ROS levels. EGCG suppressed hemin-induced cell proliferation and cell cycle regulatory protein expression as well as mitochondrial ROS accumulation. Hemin increased nuclear factor erythroid-2-related factor 2 (Nrf2) expression, but decreased Keap1 expression. EGCG enhanced hemin-induced Nrf2 and antioxidant gene expression. Nrf2 inhibitor reversed EGCG reduced cell proliferation and cell cycle regulatory protein expression. In AOM/DSS mice, hemin treatment induced hyperplastic changes in colon tissues, inhibited by EGCG supplementation. EGCG reduced the hemin-induced numbers of total aberrant crypts and malondialdehyde concentration in the AOM/DSS model. Conclusions: We demonstrated that EGCG reduced hemin-induced proliferation and colon carcinogenesis through Nrf2-inhibited mitochondrial ROS accumulation.

Effect of n-6/n-3 fatty acid ratio on metabolic partitioning in hyperlipidemic rats (n-6/n-3 지방산 비율이 고지혈증 랫드의 지질대사 분할에 미치는 영향)

  • Lee, Seunghyung;Um, Kyung-Hwan;Park, Byung-Sung
    • Journal of the Korean Applied Science and Technology
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    • v.35 no.3
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    • pp.643-653
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    • 2018
  • This study was investigated the mechanism of action of n-6/n-3 fatty acid ratio on the metabolic partitioning of blood glycerolipids by in vivo monitoring technique in hyperlipidemic animal model rats. The ratio of cholesteryl 14C-oleate metabolized in the liver of total glycerolipids was lower in the order of n-6/n-3 ratios of 4:1, 15:1, 30:1 and control group (p<0.05). The secretion amount of phospholipid was higher in the order of n-6/n-3 ratio 4:1, 15:1, 30:1 than the control (p<0.05). The secretion amount of triglyceride was lower in especially 4:1, in order of n-6/n-3 4:1, 15:1 and 30:1 compared with the control. The ratio of phospholipid partitioning to total glycerolipid was high in orfer of n-6/n-3 ratio 4:1, 15:1, 30:1 and control (p<0.05). The triacylglycerol partitioning (%) via liver was higher 72.97, 75.93, 78.12% in n-6/n-3 4;1, 15:1, 30:1, respectively than the control of 82.25%, according to increased n-6/n-3 (p<0.05). The phospholipid partitioning (%) was lower 25.15, 18.87, 18.15% in n-6/n-3 4;1, 15:1, 30:1, respectively, compared to control 11.04%, according to increased n-6/n-3 (p<0.05).

The Effect of Inulin Supplementation on Blood Lipid Levels, and Fecal Excretion of Bile Acid and Neutral Sterol in Korean Postmenopausal Women (폐경 후 한국 여성에서 이눌린 보충이 혈중 지질 농도와 변 담즙산 및 중성 스테롤 배설에 미치는 영향)

  • 이은영;김윤영;장기효;강순아;조여원
    • Journal of Nutrition and Health
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    • v.37 no.5
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    • pp.352-363
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    • 2004
  • Lipid-lowering effects of the inulin have been demonstrated in animal, yet attempts to reproduce similar effects in humans have generated conflicting results. In this study, the lipid-lowering potential of inulin and especially its effect on bile acid and neutral sterol excretion were investigated in Korean postmenopausal women. Nineteen postmenopausal women were randomly divided into two groups in a double-blind parallel design and consumed one of two supplements for 12 weeks; placebo of 8g maltodextrins/sucrose mixture (placebo group) or 8g inulin (inulin group). There were no significant changes in body weight during the supplementation period in either inulin or placebo group. Dietary consumption of animal fat in both group tended to decrease after 12 weeks of experiment. Intake of cholesterol was lower in placebo group, whereas the decrease of cholesterol intake in inulin group did not reach statistical significance after 12 weeks. The levels of serum total cholesterol (TC) and LDL-cholesterol (LDL-C) were significantly decreased in both placebo (p<0.05) and inulin group (p<0.01) after supplementation for 12 weeks compared with the baseline. The levels of serum triglyceride (TG) and HDL-cholesterol (HDL-C) were not significantly affected by inulin supplements, but atherogenic index (AI) and LDL-C/HDL-C ratio (LHR) as a predictor for coronary heart disease were improved (p<0.01) significantly after inulin supplementation. Therefore, inulin supplement may decrease the risk of cardiovascular disease via improving blood cholesterol level. Fecal weight and pH were not changed after 12 weeks of supplementation. There were no statistically significant changes for the fecal short-chain fatty acids (SCFAs). In inulin group, fecal deoxycholic acid (DCA) was significantly lowered compared with the baseline (p<0.05) whereas other bile acids were not changed. During the 12 weeks of intervention, no differences were found in fecal excretion of neutral sterol in the two groups. In summary, dietary inulin decreases serum TC, LDL-C, AI, LHR and lowers excretion of fecal DCA in the Korean postmenopausal women. These results support the use of inulin for reducing risk factors for hyperlipidemic postmenopausal women. However, the exact mechanism (s) responsible for the blood lipid lowering action of inulin including altered fecal bile acid remain to be elucidated.

Acute toxicity, Dermal and Ocular Irritation Studies of Taglisodog-eum ointment (탁리소독음 피부외용제형의 급성경피독성시험, 피부자극시험 및 안점막자극시험)

  • Lee, Jung Bok;Choi, Jae Hwan;Kim, Hee Taek;Kim, Yun Kyung;Yu, Young Beob
    • Herbal Formula Science
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    • v.24 no.4
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    • pp.289-300
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    • 2016
  • Objectives : Taglisodog-eum(TSE), a poly herbal formula, has been widely used to improve carbuncles by removing inflammation of the lymphatic channels in Traditional Korean Medicine. We previousely reported the action mechanism of TSE on experimental atopic dermatitis and the establishment of formulation for TSE ointment. In this study, we examined the toxicity test on skin and eye irritation by TSE ointment to prove the safety of Taglisodog-eum ointment in clinical use. Methods : Acute skin toxicity of the TSE ointment was evaluated in Sprague-Dawley(SD) rats. After dermal administration of TSE ointment(2,000mg/kg), body weight, mortality, and clinical signs of the rats were observed for 14days. Primary skin irritation and ocular irritation tests for TSE ointment were performed in male New Zealand White Rabbits. In dermal and ocular irritation test, body weight, mortality, clinical signs, Primary Irritation Index(P.I.I.), and The Index of Acute Ocular Irritaion(I.A.O.I.) of rabbit were observed after applying at abraded skin and eye balls with Taglisodog-eum ointment. Results : In the results of acute skin toxicity, no significant differences were found in body weight, the clinical sign and the mortality between control and TSE ointment treated group. In primary dermal irritation test, body weight, the clinical sign and the mortality were not significantly changed and Primary Irritation Index(P.I.I.) was 0.8, indicating TSE ointment as weak irritant material. In ocular irritation test, The Index of Acute Ocular Irritaion was 0.0, indicating TSE ointment as non-irritating to the eye of the rabbits. To evaluate toxicity of the TSE ointment in animal test, body weight, the clinical signs, the skin and eye irritation check were conducted; TSE ointment was considered to be weak dermal irritant in test animals. The no response of eye irritation test was observed in this experimental condition. Conclusions : According to the above toxicity test, We consider that this results is helpful for saying about the safety of TSE ointment in clinical use.

Antiviral Effect of Retro-2.1 against Herpes Simplex Virus Type 2 In Vitro

  • Dai, Wenwen;Wu, Yu;Bi, Jinpeng;Wang, Jingyu;Wang, Shuai;Kong, Wei;Barbier, Julien;Cintrat, Jean-Christophe;Gao, Feng;Jiang, Zhengran;Gillet, Daniel;Su, Weiheng;Jiang, Chunlai
    • Journal of Microbiology and Biotechnology
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    • v.28 no.6
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    • pp.849-859
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    • 2018
  • Herpes simplex virus type 2 (HSV-2) infection has been a public health concern worldwide. It is the leading cause of genital herpes and a contributing factor to cervical cancer and human immunodeficiency virus (HIV) infection. No vaccine is available yet for the treatment of HSV-2 infection, and routinely used synthetic nucleoside analogs have led to the emergence of drug resistance. The small molecule $Retro-2^{cycl}$ has been reported to be active against several pathogens by acting on intracellular vesicle transport, which also participates in the HSV-2 lifecycle. Here, we showed that Retro-2.1, which is an optimized, more potent derivative of $Retro-2^{cycl}$, could inhibit HSV-2 infection, with 50% inhibitory concentrations of $5.58{\mu}M$ and $6.35{\mu}M$ in cytopathic effect inhibition and plaque reduction assays, respectively. The cytotoxicity of Retro-2.1 was relatively low, with a 50% cytotoxicity concentration of $116.5{\mu}M$. We also preliminarily identified that Retro-2.1 exerted the antiviral effect against HSV-2 by a dual mechanism of action on virus entry and late stages of infection. Therefore, our study for the first time demonstrated Retro-2.1 as an effective antiviral agent against HSV-2 in vitro with targets distinct from those of nucleoside analogs.

The Role of Sympathy and Moral Nomativity in Moral Sentimentalism of Hutcheson, Hume, and Adam Smith (허치슨, 흄, 아담 스미스의 도덕감정론에 나타난 공감의 역할과 도덕의 규범성)

  • Yang, Sunny
    • Journal of Korean Philosophical Society
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    • no.114
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    • pp.305-335
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    • 2016
  • In the eighteenth century, the scottish philosophers Francis Hutcheson, David Hume and Adam Smith share the idea that morality comes from moral sense, which is a feeling of approval or disapproval of agent's motive and action. However, they have the different views in explaining the mechanism that generates the moral sentiments. Hutcheson takes a moral sense to be a unique mental faculty that is innate to all humans, and regards it as being guaranteed by supernatural apparatus like divine Providence. Hume and Smith reject Hutcheson's concept of internal moral sense and take a stage further Hutcheson's projects of internalisation by naturalizing morality in terms of the principle of sympathy. It is widely held that Hume's moral sentimentalism is essentially similar to Adam Smith's. Though there are important points of contact between Smith's account of sympathy and Hume's, the differences are considerable. The chief of them lies in the fact that Hume grounds our approval of virtue on our recognition of its utility and convention, and Smith does not. Smith grounds our approval of virtue on the impartial spectator's judgment, i.e., conscience. Hence for Smith, the impartial spectator is the one that bridges the gap between particularity and universality and works the vehicle of practical reason. Given this, in this paper, first, I will clarify the difference between Hume's and Adam Smith's understandings of sympathy. Second, I will elucidate how they explain the process to produce the moral sentiments based on their understandings of sympathy. I shall finally explicate in what way Hume's and Smith's theories on sympathy work as moral normativity.

Effects of Siegesbckiae Herba on the Brain Ischemia (희렴 이 뇌허혈에 미치는 효과)

  • Han Jong Hyun;Na Han Il;Kyu Ho Kyung;Jo Kyu Won;Kim Kyung Soo
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.18 no.6
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    • pp.1643-1651
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    • 2004
  • This experimental study was designed to investigate the effects of SIEGESBECKIAE HERBA extract (SHE) on the change of cerebral hemodynamics 〔regional cerebral blood flow (rCBF) and mean arterial blood pressure(MABP)〕 in normal condition and cerebral ischemic rats, and to determine the mechanism of action of SHE. This study was designed to investigate whether or not SHE inhibit lactate dehydrogenase (LDH) activity in neuronal cells and cytokines production in serum of cerebral ischemic rats. The results were as follows SHE increased rCBF significantly in a dose-dependent manner, but MABP was not changed by SHE in normal rats. The SHE-induced increase in rCBF was significantly inhibited by pretreatment with indomethacin (IDN), an inhibitor of cyclooxygenase but was increased by methylene blue (MTB), an inhibitor of guanylate cyclase. SHE inhibited lactate dehydrogenase (LDH) activity significantly in neuronal cells. rCBF was increased significantly and stably by SHE(10㎎/㎏, i.p.) during the period of cerebral reperfusion, which contrasted with the findings of rapid and marked increase in control group in ischemic rats. In serum by drawing from femoral arterial blood after middle cerebral arterial occlusion(MCAO) for 1hr and reperfusion for 1hr, the sample group was decreased IL-1β production significantly compared to that of the control group. In serum by drawing from femoral arterial blood after MCAO 1hr and reperfusion 1hr, sample group decreased TNF-α production significantly compared to that of the control grolilp. In serum by drawing from femoral arterial blood after reperfusion 1hr, sample group increased TGF-β production significantly compared to that of the control group. In serum by drawing from femoral arterial blood after MCAO for 1hr and reperfusion for 1hr, IL-10 production of the sample group was similar to that of control group. These results suggested that SHE had inhibitive effect on the brain damage by inhibited LDH activity, IL-1β and TNF-α production, but accelerated TGF-β production.