• Title/Summary/Keyword: in vitro metabolite

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A prebiotic fiber increases the formation and subsequent absorption of compound K following oral administration of ginseng in rats

  • Kim, Kyung-Ah;Yoo, Hye Hyun;Gu, Wan;Yu, Dae-Hyung;Jin, Ming Ji;Choi, Hae-Lim;Yuan, Kathy;Guerin-Deremaux, Laetitia;Kim, Dong-Hyun
    • Journal of Ginseng Research
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    • v.39 no.2
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    • pp.183-187
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    • 2015
  • Background: Gut microflora play a crucial role in the biotransformation of ginsenosides to compound K (CK), which may affect the pharmacological effects of ginseng. Prebiotics, such as NUTRIOSE, could enhance the formation and consequent absorption of CK through the modulation of gut microbial metabolic activities. In this study, the effect of a prebiotic fiber (NUTRIOSE) on the pharmacokinetics of ginsenoside CK, a bioactive metabolite of ginsenosides, and its mechanism of action were investigated. Methods: Male Sprague-Dawley rats were given control or NUTRIOSE-containing diets (control diet + NUTRIOSE) for 2 wk, and ginseng extract or vehicle was then orally administered. Blood samples were collected to investigate the pharmacokinetics of CK using liquid chromatography-tandem mass spectrometry. Fecal activities that metabolize ginsenoside Rb1 to CK were assayed with fecal specimens or bacteria cultures. Results: When ginseng extract was orally administered to rats fed with 2.5%, 5%, or 10% NUTRIOSE containing diets, the maximum plasma concentration ($C_{max}$) and area under the plasma concentration-time curve values of CK significantly increased in a NUTRIOSE content-dependent manner. NUTRIOSE intake increased glycosidase activity and CK formation in rat intestinal contents. The CK-forming activities of intestinal microbiota cultured in vitro were significantly induced by NUTRIOSE. Conclusion: These results show that prebiotic diets, such as NUTRIOSE, may promote the metabolic conversion of ginsenosides to CK and the subsequent absorption of CK in the gastrointestinal tract and may potentiate the pharmacological effects of ginseng.

The Effects of MeOH Extract of Hopea chinensis (Merr.) Hand.-Mazz. on the Metabolism of Amyloid Precursor Protein in Neuroblastoma Cells (Hopea chinensis (Merr.) Hand.-Mazz. 메탄올 추출물이 신경세포에서 아밀로이드 전구 단백질 대사에 미치는 영향)

  • Chandra, Shrestha Abinash;Kim, Ju Eun;Ham, Ha Neul;Jo, Youn Jeong;Bach, Tran The;Eum, Sang Mi;Leem, Jae Yoon
    • Korean Journal of Pharmacognosy
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    • v.49 no.2
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    • pp.182-187
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    • 2018
  • Many plant derived phytochemicals have been considered as the main therapeutic strategy against Alzheimer's disease (AD). AD is a progressive neurodegenerative disorder, and the most predominant cause of dementia in the elderly. Cholinergic deficit, senile plaque/${\beta}$-amyloid ($A{\beta}$) peptide deposition and oxidative stress have been identified as three main pathogenic pathways which contribute to the progression of AD. We screened many different plant species for their effective use in both modern and traditional system of medicines. In this study, we tested that MeOH extract of the stem bark of Hopea chinensis (Merr.) Hand.-Mazz. (HCM) affects on the processing of Amyloid precursor portein (APP) from the APPswe over-expressing Neuro2a cell line. We showed that HCM reduced the secretion level of $A{\beta}42$ and $A{\beta}40$ in a dose dependent manner. We found that HCM increased over 1.5 folds of the secretion level of $sAPP{\alpha}$, a metabolite of ${\alpha}$-secretase. Furthermore, we found that HCM inhibited acetylcholinesterase activity in vitro. We suggest that the stem bark of Hopea chinensis may be a useful source to develop a therapeutics for AD.

Oral Administration of Alcohol-Tolerant Lactic Acid Bacteria Alleviates Blood Alcohol Concentration and Ethanol-Induced Liver Damage in Rodents

  • Misun Yun;Hee Eun Jo;Namhee Kim;Hyo Kyeong Park;Young Seo Jang;Ga Hee Choi;Ha Eun Jo;Jeong Hyun Seo;Ji Ye Mok;Sang Min Park;Hak-Jong Choi
    • Journal of Microbiology and Biotechnology
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    • v.34 no.4
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    • pp.838-845
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    • 2024
  • Excessive alcohol consumption can have serious negative consequences on health, including addiction, liver damage, and other long-term effects. The causes of hangovers include dehydration, alcohol and alcohol metabolite toxicity, and nutrient deficiency due to absorption disorders. Additionally, alcohol consumption can slow reaction times, making it more difficult to rapidly respond to situations that require quick thinking. Exposure to a large amount of ethanol can also negatively affect a person's righting reflex and balance. In this study, we evaluated the potential of lactic acid bacteria (LAB) to alleviate alcohol-induced effects and behavioral responses. Two LAB strains isolated from kimchi, Levilactobacillus brevis WiKim0168 and Leuconostoc mesenteroides WiKim0172, were selected for their ethanol tolerance and potential to alleviate hangover symptoms. Enzyme activity assays for alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) were then conducted to evaluate the role of these bacteria in alcohol metabolism. Through in vitro and in vivo studies, these strains were assessed for their ability to reduce blood alcohol concentrations and protect against alcohol-induced liver damage. The results indicated that these LAB strains possess significant ethanol tolerance and elevate ADH and ALDH activities. LAB administration remarkably reduced blood alcohol levels in rats after excessive alcohol consumption. Moreover, the LAB strains showed hepatoprotective effects and enhanced behavioral outcomes, highlighting their potential as probiotics for counteracting the adverse effects of alcohol consumption. These findings support the development of functional foods incorporating LAB strains that can mediate behavioral improvements following alcohol intake.

Anti-proliferative and Antioxidant Activities of 1-methoxy-3-methyl-8-hydroxy-anthraquinone, a Hydroxyanthraquinoid Extrolite Produced by Amycolatopsis thermoflava strain SFMA-103

  • Kumar, C. Ganesh;Mongolla, Poornima;Chandrasekhar, Cheemalamarri;Poornachandra, Yedla;Siva, Bandi;Babu, K. Suresh;Ramakrishna, Kallaganti Venkata Siva
    • Microbiology and Biotechnology Letters
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    • v.45 no.3
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    • pp.200-208
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    • 2017
  • Actinobacteria are prolific producers of a large number of natural products with diverse biological activities. In the present study, an actinobacterium isolated from sunflower rhizosphere soil sample collected from Medak, Andhra Pradesh, South India was identified as Amycolatopsis thermoflava strain SFMA-103. A pigmented secondary metabolite in culture broth was extracted by using methanol and it was further purified by silica gel column chromatography with methanol-chloroform solvent system. Structural elucidation studies based on UV-visible, 1D and 2D-NMR, FT-IR, and mass spectroscopic analyses confirmed the structure as 1-methoxy-3-methyl-8-hydroxy-anthraquinone. It showed significant in vitro anticancer activity against lung cancer and lymphoblastic leukemia cells with $IC_{50}$ values of 10.3 and $16.98{\mu}M$, respectively. In addition, 1-methoxy-3-methyl-8-hydroxy-anthraquinone showed good free radical scavenging activity by DPPH method with an $EC_{50}$ of $18.2{\mu}g/ml$. It also showed other promising superoxide radical scavenging, nitric oxide radical scavenging and inhibition of lipid peroxidation activities. This is a first report of anti-proliferative and antioxidant activities of 1-methoxy-3-methyl-8-hydroxy-anthraquinone isolated from A. thermoflava strain SFMA-103 which may find potential application in biotechnological and pharmaceutical fields.

Synthesis of New Boron Derived Compounds; Anticancer, Antioxidant and Antimicrobial Effect in Vitro Glioblastoma Tumor Model

  • Koldemir-Gunduz, Meliha;Aydin, Hasan Emre;Berikten, Derya;Kaymak, Gullu;Kose, Dursun Ali;Arslantas, Ali
    • Journal of Korean Neurosurgical Society
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    • v.64 no.6
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    • pp.864-872
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    • 2021
  • Objective : The aim of our study is to investigate the cytotoxic, antioxidant, and antimicrobial effects of newly synthesized boron compounds in U87MG glioblastoma cell treatment. Methods : We synthesized boron glycine monoester (BGM) and boron glycine diester (BGD) structures containing boron atoms and determined their cytotoxic activities on glioblastoma by the MTT method. The inhibitory concentration 50 (IC50) value was calculated with GraphPad Prism 5.0 program. The IC50 values were administered 48 hours on U87MG glioblastoma cell. Catalase (CAT), acid phosphatase (ACP) and alkaline phosphatase (ALP) enzyme activity, malondialdehyde (MDA), total glutathione (GSH), and total protein levels were detected using spectrophotometric methods. We determined the antimicrobial activities of BGM and BGD with the disc diffusion method. Results : After 48 hours of BGM and BGD application to U87MG glioblastoma cells, we found the IC50 value as 6.6 mM and 26 mM, respectively. CAT and ACP enzyme activities were decreased in BGM and BGD groups. MDA which is a metabolite of lipid peroxidation was increased in both boron compounds groups. GSH level was reduced especially in BGD group. BGM and BGD have been found to be antimicrobial effects. Conclusion : Boron compounds, especially the BGM, can provide a new therapeutic approach for the treatment of glioblastoma with their anticancer, antioxidant, and antimicrobial effects.

Ginseng saponin metabolite 20(S)-protopanaxadiol relieves pulmonary fibrosis by multiple-targets signaling pathways

  • Guoqing Ren;Weichao Lv;Yue Ding;Lei Wang;ZhengGuo Cui;Renshi Li;Jiangwei Tian;Chaofeng Zhang
    • Journal of Ginseng Research
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    • v.47 no.4
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    • pp.543-551
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    • 2023
  • Background: Panax ginseng Meyer is a representative Chinese herbal medicine with antioxidant and anti-inflammatory activity. 20(S)-Protopanaxadiol (PPD) has been isolated from ginseng and shown to have promising pharmacological activities. However, effects of PDD on pulmonary fibrosis (PF) have not been reported. We hypothesize that PDD may reverse inflammation-induced PF and be a novel therapeutic strategy. Methods: Adult male C57BL/6 mice were used to establish a model of PF induced by bleomycin (BLM). The pulmonary index was measured, and histological and immunohistochemical examinations were made. Cell cultures of mouse alveolar epithelial cells were analyzed with Western blotting, coimmunoprecipitation, immunofluorescence, immunohistochemistry, siRNA transfection, cellular thermal shift assay and qRT-PCR. Results: The survival rate of PPD-treated mice was higher than that of untreated BLM-challenged mice. Expression of fibrotic hallmarks, including α-SMA, TGF-β1 and collagen I, was reduced by PPD treatment, indicating attenuation of PF. Mice exposed to BLM had higher STING levels in lung tissue, and this was reduced by phosphorylated AMPK after activation by PPD. The role of phosphorylated AMPK in suppressing STING was confirmed in TGF-b1-incubated cells. Both in vivo and in vitro analyses indicated that PPD treatment attenuated BLM-induced PF by modulating the AMPK/STING signaling pathway. Conclusion: PPD ameliorated BLM-induced PF by multi-target regulation. The current study may help develop new therapeutic strategies for preventing PF.

Toxic action of benfuracarb via oxidative bioactivation process by cytochrome $P_{450}$ (Procarbamate계 살충제 benfuracarb의 산화적 활성화 과정을 통한 독성발현)

  • Yu, Yong-Man;Kim, Eun-H.;Kim, Song-Mum;Hur, Jang-Hyun
    • The Korean Journal of Pesticide Science
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    • v.7 no.1
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    • pp.45-50
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    • 2003
  • This study was conducted to understand the role of oxidative enzyme cytochrome $P_{450}$ in the bioactivation of benfuracarb and to know metabolites of benfuracarb by cytochrome $P_{450}$. The bimolecular imhibition rate constant $(k_i)$ of benfuracarb on acetylcholinesterase (AChE) was as low as $1.1{\times}10^3\;M^{-1}\;min^{-1}$, suggesting that benfuracarb should be activated for its toxic action. The potency of benfuracarb on AChE in the oxidase system (cytochrome $P_{450}$ + NADPH) in vitro was 10-fold higher than that of control (cytochrome $P_{450}$). Such a similar result was also found in the oxidase + PBO system. In vivo the $I_{50}$ of benfuracarb was 22.7mg $kg^{-1}$, but pie-treatment of piperonyl butoxide (PBO) reduced the $I_{50}$ by >100mg $kg^{-1}$. This result suggests that cytochrome $P_{450}$ was involved in the activation of benfuracarb. Using microsomal oxidase system, metabolites of benfuracarb were elucidated. Fifty-eight percent of benfuracarb was converted to carbofuran, a major toxic metabolite, in the oxidase system, while only less than two percent of benfuracarb was converted to carbofuran in the oxidase + PBO system. These results also suggest that cytochrome $P_{450}$ was involved in the activation of benfuracarb. Overall results indicate that cytochrome $P_{450}$ could be involved in the bioactivation of benfuracarb to carbofuran.

3,4-Dihydroxytoluene Inhibits Epidermal Growth Factor-induced Cell Transformation in JB6 P+ Mouse Epidermal Cells by Suppressing Raf-1 (3,4-Dihydroxytoluene의 Raf-1 신호전달체계 억제를 통한 암예방 효능)

  • Kim, Ji An;Kim, Ji Hye;di Ruccio, Eric;Kang, Nam Joo
    • The Korean Journal of Food And Nutrition
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    • v.28 no.1
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    • pp.111-118
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    • 2015
  • In summary, the rutin metabolite DHT significantly reduced EGF-induced neoplastic transformation in JB6 P+ cells. This inhibition was mediated mainly by blocking the Raf/MEK/ERK signaling pathway and subsequent suppression of AP-1 activities. DHT attenuated Raf-1 kinase activity by directly binding to Raf-1 in vitro and ex vivo. Taken together, these results suggest that Raf-1 may be a critical molecular target to suppress DHT-induced neoplastic transformation, which is mainly attributable to the chemopreventive potential of several foods containing rutin.

Micropropagation of Lobelia chinensis Lour.: Influence of Medium Parameters on Plant Regeneration, Antioxidant Activity, and Secondary Metabolite Accumulation

  • Xinlei Bai;Han-Sol Lee;Hosakatte Niranjana Murthy;Hyuk-Joon Kwon;Soo-Ho Yeon;Jae-Yeong Ju;So-Young Park
    • Korean Journal of Plant Resources
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    • v.37 no.3
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    • pp.225-234
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    • 2024
  • Chinese lobelia (Lobelia chinensis Lour.) is an important medicinal plant that is used in traditional Chinese, Korean, and Japanese medicine. The goal of the current study was to develop an in vitro propagation technique for Lobelia chinensis. We have examined the effects of different media compositions on the regeneration of shoots from nodal cultures of Lobelia chinensis, including Murashige and Skoog (MS), Gamborg (B5), Schenk and Hildebrandt (SH), Woody plant (WPM), Chu (N6), and Nitsch and Nitsch (NLN) media. Similar to this, shoot regeneration was examined using MS medium of double (2.0), full (1.0), half (0.5), and quarter (0.25) strengths. The regeneration of shoots was also examined with additions of 0, 1, 3, 5, and 7% (w/v) sucrose to MS media. For axillary shoot regeneration, full-strength MS medium supplemented with 3% (w/v) sucrose was shown to be the most effective of all the evaluated factors. On this medium, nodal explants optimally regenerated 4.5 shoots per explant and subsequently shoots involved in rooting on the same medium. The regenerated plants possessed abundant phenolics, flavonoids, and DPPH, ABTS, and FRAP antioxidant activities. High performance liquid chromatographic examination (HPLC) of the regenerated plants revealed an accumulation of myricetin and catechin in higher amounts.

The Beneficial Effects of Ferulic Acid supplementation during In Vitro Maturation of Porcine Oocytes on Their Parthenogenetic Development

  • Lee, Kyung-Mi;Hyun, Sang-Hwan
    • Journal of Embryo Transfer
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    • v.32 no.4
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    • pp.257-265
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    • 2017
  • Ferulic Acid (FA) is a metabolite of phenylalanine and tyrosine, a phenolic compound commonly found in fruits and vegetables. Several studies have shown that FA has various functions such as antioxidant effect, prevention of cell damage from irradiation, protection from cell damage caused by oxygen deficiency, anti-inflammatory action, anti-aging action, liver protective effect and anti-cancer action. In this study, we investigated the maturation rate, intracellular glutathione (GSH) and reactive oxygen species (ROS) of porcine oocytes by adding FA to the in vitro maturation (IVM) medium and examined subsequent embryonic developmental competence at 5% oxygen through parthenogenesis. There is no significant difference between the control group ($0{\mu}M$) and treatment groups ($5{\mu}M$, $10{\mu}M$, $20{\mu}M$) on maturation rates. Intracellular GSH levels in oocyte treated with $5{\mu}M$ of FA significantly increased (P < 0.05), and $20{\mu}M$ of FA revealed significant decrease (P < 0.05) in intracellular ROS levels compared with the control group. Oocytes treated with FA exhibited significantly higher cleavage rates (79.01% vs 89.19%, 92.20%, 90.89%, respectively) than the control group. Oocytes treated with $10{\mu}M$ showed significantly higher blastocyst formation rates (28.3% vs 40.3%, respectively) after PA than the control group. Total cell numbers in blastocyst of $10{\mu}M$ FA displayed significantly higher (39.4 vs 51.9, respectively) than the control group. In conclusion, these results suggested that treatment with FA during IVM improved the developmental potential of porcine embryos by increasing intracellular GSH synthesis and reducing ROS levels. Also, there was an improvement of cleavage rate, blastocyst formation and total cell numbers in blastocysts. It might be associated with Keap1-Nrf2 pathway as an antioxidant regulate pathway that plays a crucial role in determining the sensitivity of cells to oxidative damages by regulating the basal and inducible expression of enzymes which is related to detoxification and anti-oxidative effects, stress response enzymes and/or proteins and ABC transporters.