• Proceedings of the Plant Resources Society of Korea Conference
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• 2018.04a
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• pp.67-67
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• 2018

Trichoderma species are a rich source of metabolites, but less known for biomedical potential. This work deals with antibacterial and antioxidant potentials of intracellular non-cytotoxic metabolites, extracted from Trichoderma atroviride (KNUP001). A total of 53 fractions was collected by column chromatography and tested for cytotoxicity by MTT assay. Only one fraction (F41) was found to be non-toxic to Vero cells with $95.4{\pm}0.61%$ of survival. The F41 was then subjected to chemical analysis, antibacterial and antioxidant assays. The F41 at $500{\mu}g.ml^{-1}$ showed the total antioxidant of $48.70{\pm}2.90%$, DPPH radical scavenging activity of $37.25{\pm}2.25$, nitric oxide (NO) radical scavenging activity of $54.55{\pm}1.95$ and $H_2O_2$ radical scavenging activity of $43.75{\pm}3.21$. The F41 at $25{\mu}g.ml^{-1}$ displayed antibacterial activity against E. coli ($14.25{\pm}0.2mm$), P. mirabilis ($10.4{\pm}0.6mm$), S. dysenteriae ($18.6{\pm}03mm$), S. paratyphi A ($14.1{\pm}1.1mm$), E. aerogenes ($5.6{\pm}0.4mm$) and S. marcescens ($14.25{\pm}0.2mm$). GC-MS analysis revealed the dominant presence of oleic acid C 18.1 (63.18%), n-hexadecanoic acid (6.17%), and ethyl oleate (4.93%) and potent molecules such as 8-[(2E)-2-(3-hydroxybenzylidene)hydrazinyl]-1,3,7-trimethyl-3,7-dihydro-1H-purine-2,6-dione, 2-(Dimethylamino)ethyl (1Z)-N-hydroxy-2-(4-morpholinyl)-2-oxoethanimidothioate, Fluorene in the F41, and virtual study revealed that these molecules are likely responsible for the antibacterial activities of F41. Hence, further investigation deserves on purification and characterization of the active metabolites from T. atroviride strain KNUP001 towards developing molecular leads to effective antibacterial drugs, and non-toxic to host cells.

• Journal of Ginseng Research
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• v.17 no.1
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• pp.52-60
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• 1993

Panax ginseng has been extensively used in the traditional oriental medicine as a restorative, tonic and Prophylactic agent. Recently, several reports regarding to anticancer effects of Panax ginseng has accumulated. These studies emphasized the fact that the anticancer activities might be due to a glycoside group called ginsenoside or pan.u saponin which has a water soluble characteristic. However, the authors and collaborates demonstrated that a highly lipid soluble component in extract of Panax ginseng roots contains a considerable cytotoxic activities against marine leukemic cells (L1210, P388) and human censer cells (HRT-18, HT-29, HCT48). This study was devised to observe the cytotoxic activities of Petroleum-ether extract of Panax giuseng roots (crude GBD and its Partially Purified fraction from silicic acid column chromatography (7 : 3 GX) against sarcoma-180 (5-180) and Walker carcinosar- coma 256 (Walker 256) in vivo, and murine leukemic Lymphocytes (L1210) and human rectal cancer cells (HRT-18) and human colon cancer cells (HT-29 and HCT48) in vitro. Each cell-line was cultured in medium containing serial concentration of the crude GX or 7 : 3 GX in vitro. A highly lipid soluble compound in the extract of Panax ginseng root was cytocidal to murine leukemic cells and human colon and rectal cancer cells in vitro. In the meantime, ginseng saponin derivatives did not have cytotoxic effects at its corresponding concentration. The growth rates of the cancer cells in medium containing ginseng extracts were inhibited gradually to a significant degree roughly in proportion to the increase of the extract concentration. The cytotoxic activity of 7 : 3 GX was about 3 times more potent than that of crude GX, one unit of cytotoxic activity against L1210 cells being equivalent to 2.54 Ug and 058 Ug for the crude GX and 7 : 3 GX, respectively. The Ri value of the active compound on silica- gel thin layer chromatography with petroleum-ether/ethyl ether/acetic acid mixture (90 : 10 : 1, v/v/v) as a developing so lvent was 053. While, the Panaxydol and Panaxynol as active compounds were purified from Petroleum-ether extract of Panax ginseng root by Drs. Ahn and Kim, and author found out that the one unit of cytotoxic activity of the Panaxydol and Panaxynol against L1210 cells being equivalent to 056 Ug and 0.3918 respectively. The survival times of mice inoculated with S-180 cells were extended about 1.5 to 2 times by the 7 : 3 GX treatment compared with their control group. The significantly decreased hemoglobin values of rats after inoculation with Walker 256 were recovered to normal range by oral administration of the crude Gt The synthetic levels of protein, DNA and RNA in human colon and rectal cancer cells were significantly diminished by treatment with the crude GX, which can explain a part of the origin of its anticancer activity.

• Korean Journal of Food Science and Technology
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• v.41 no.1
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• pp.87-92
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• 2009

The antioxidant properties and protective effects of Inula britannica on ${H_2}{O_2}$-induced SH-SY5Y neuroblastoma cell damage were investigated. A series of solvent fractions, including hexane(Fr.H), petroleum ether, chloroform, ethyl acetate(Fr.EA), and water fraction(Fr.W), were prepared from the 70% methanol extracts of Inula britannica. Fr.W had the highest total contents of phenolics and flavonoids, followed by Fr.EA. The antioxidant properties of the fractions were also evaluated by analyzing their scavenging activities on 1,1-diphenyl-2-picrylhydrazyl(DPPH) radicals, 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radicals, and nitric oxide. Fr.W showed the strongest activities in all assays. The concentrations of Fr.W that resulted in 50% reductions of the DPPH and ABTS radicals were 20.7 ${\mu}g$/mL and 39.4 ${\mu}g$/mL, respectively. Fr.W showed the weakest cytotoxic activities on the SH-SY5Y cells, whereas it effectively protected ${H_2}{O_2}$-induced cell death, increasing cell survival by 35.0-77.0% at a concentration range of 62.5-250 ${\mu}g$/mL. In this range, Fr.W also significantly decreased intracellular ROS levels by 34-39%. Overall, the antioxidant properties of Inula britannica can contribute to rescuring neuronal cells from oxidative stress-induced cell injury.

• Journal of Life Science
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• v.7 no.4
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• pp.316-321
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• 1997

The effects of the silver ion-exchanged water treatment agent (Ag-Os) upon E. coli RB 797 and Bacillus sp. have been discussed in this study. Silver ion causes a number of toxic effects with no known biological function. Silver ion-exchanged water treatment agent (Ag-Os) using oyster shell here showed antimicrobial activities. the soluble form of silver ion in water is more toxic to the growth of Bacillus sp. than that of E. Coli RB 797. The minium amount of Ag-Os needed for growth inhibition is 0.2 mg/ml for E. Coli RB 797 and 0.02 mg/ml for Bacillus sp., which is consistant with the data of the survival cell fraction. Binding studies suggested that binding of silver to the cell surface was a rapid, metabolic-independent process and different from active transport. Bacillus sp. showed more binding than E. Coli RB 797. Reducing substances of the cell cultures in the presence of Ag-Os was detected using Methylen blue as an indicator. From these results, we suggest that Ag-Os is effective as an antimicrobial agent on E. Coli RB 797 and Bacillus sp. and silver binds to the cells through rapid, metabolic-independent process and might complex to sulfur group in the cells for its toxicity.

• Korean Journal of Food Science and Technology
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• v.54 no.2
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• pp.209-217
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• 2022

In this study, Enterococcus faecalis BMSE-HMP005 isolated from human breast milk demonstrated antimicrobial effects against multidrug-resistant (MDR) bacterial strains. The bacteriocin produced by E. faecalis BMSE-HMP005 was fractionated using reverse-phase high-performance liquid chromatography. This fraction showed antimicrobial effects against both gram-positive and gram-negative MDR bacteria. No hemolytic reactions were observed. E. faecalis BMSEHMP005 was resistant to vancomycin; however, kanamycin, ampicillin, and erythromycin showed minimum inhibitory concentrations that were lower than the acceptable range provided by the European Food Safety Authority. For artificial gastric juice and bile acid, the survival rates were 98.67% and 95.70%, respectively. These results show the potential utility of E. faecalis BMSE-HMP005 as a probiotic with remarkable antimicrobial effects against MDR bacteria.

• Biomolecules & Therapeutics
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• v.31 no.1
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• pp.73-81
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• 2023

Sirtuins (SIRTs) belong to the nicotinamide adenine dinucleotide (NAD+)-dependent class III histone deacetylase family. They are key regulators of cellular and physiological processes, such as cell survival, senescence, differentiation, DNA damage and stress response, cellular metabolism, and aging. SIRTs also influence carcinogenesis, making them potential targets for anticancer therapeutic strategies. In this study, we investigated the anticancer properties and underlying molecular mechanisms of a novel SIRT1 inhibitor, MHY2251, in human colorectal cancer (CRC) cells. MHY2251 reduced the viability of various human CRC cell lines, especially those with wild-type TP53. MHY2251 inhibited SIRT1 activity and SIRT1/2 protein expression, while promoting p53 acetylation, which is a target of SIRT1 in HCT116 cells. MHY2251 treatment triggered apoptosis in HCT116 cells. It increased the percentage of late apoptotic cells and the sub-G1 fraction (as detected by flow cytometric analysis) and induced DNA fragmentation. In addition, MHY2251 upregulated the expression of FasL and Fas, altered the ratio of Bax/Bcl-2, downregulated the levels of pro-caspase-8, -9, and -3 proteins, and induced subsequent poly(ADP-ribose) polymerase cleavage. The induction of apoptosis by MHY2251 was related to the activation of the caspase cascade, which was significantly attenuated by pre-treatment with Z-VAD-FMK, a pan-caspase inhibitor. Furthermore, MHY2251 stimulated the phosphorylation of c-Jun N-terminal kinase (JNK), and MHY2251-triggered apoptosis was blocked by pre-treatment with SP600125, a JNK inhibitor. This finding indicated the specific involvement of JNK in MHY2251-induced apoptosis. MHY2251 shows considerable potential as a therapeutic agent for targeting human CRC via the inhibition of SIRT1 and activation of JNK/p53 pathway.

• Journal of the Korean Applied Science and Technology
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• v.40 no.6
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• pp.1454-1463
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• 2023

Evaluating the antioxidant efficacy using Potentillae Chinensis Herba extract, the anti-inflammatory efficacy was tested in respiratory mucosal epithelium, RAW264.7 cells, and zebrafish. As a result, antioxidant activity increased in a concentration-dependent manner in DPPH free radical scavenging and ABTS+ cation radical activities. As a result of MTT assay for cell experiments, the survival rate of NCI-H292 cells was reduced to less than 70% when treated at each concentration of 100 ㎍/ml, subsequent experiments were conducted at 50 ㎍/ml. Anti-inflammatory efficacy evaluation, NO production, TNF-𝛼, IL-1𝛽, and PGE₂ decreased, and COX-2 also decreased significantly at 50 ㎍/ml. The mucin protein expression of Potentillae Chinensis Herba extract and bioconverted extract, it was observed that MUC5AC expression was significantly reduced. In the zebrafish toxicity evaluation, concentrations below 50 ㎍/ml did not show embryotoxicity and showed anti-inflammatory efficacy by reducing NO production due to LPS. The above results are valid to be valuable for use as a functional material that suppresses inflammation by helping the expression of Potentillae Chinensis Herba's respiratory mucus proteins.

• Journal of Cardiovascular Imaging
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• v.31 no.2
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• pp.85-95
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• 2023

BACKGROUND: The prognostic utility of follow-up transthoracic echocardiography (FU-TTE) in patients with hypertrophic cardiomyopathy (HCM) is unclear, specifically in terms of whether changes in echocardiographic parameters in routine FU-TTE parameters are associated with cardiovascular outcomes. METHODS: From 2010 to 2017, 162 patients with HCM were retrospectively enrolled in this study. Using echocardiography, HCM was diagnosed based on morphological criteria. Patients with other diseases that cause cardiac hypertrophy were excluded. TTE parameters at baseline and FU were analyzed. FU-TTE was designated as the last recorded value in patients who did not develop any cardiovascular event or the latest exam before event development. Clinical outcomes were acute heart failure, cardiac death, arrhythmia, ischemic stroke, and cardiogenic syncope. RESULTS: Median interval between the baseline TTE and FU-TTE was 3.3 years. Median clinical FU duration was 4.7 years. Septal trans-mitral velocity/mitral annular tissue Doppler velocity (E/e'), tricuspid regurgitation velocity, left ventricular ejection fraction (LVEF), and left atrial volume index (LAVI) at baseline were recorded. LVEF, LAVI, and E/e' values were associated with poor outcomes. However, no delta values predicted HCM-related cardiovascular outcomes. Logistic regression models incorporating changes in TTE parameters had no significant findings. Baseline LAVI was the best predictor of a poor prognosis. In survival analysis, an already enlarged or increased size LAVI was associated with poorer clinical outcomes. CONCLUSIONS: Changes in echocardiographic parameters extracted from TTE did not assist in predicting clinical outcomes. Cross-sectionally evaluated TTE parameters were superior to changes in TTE parameters between baseline and FU at predicting cardiovascular events.

• Korean Circulation Journal
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• v.54 no.6
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• pp.311-322
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• 2024

Background and Objectives: Early diastolic mitral annular tissue (e') velocity is a commonly used marker of left ventricular (LV) diastolic function. This study aimed to investigate the prognostic implications of e' velocity in patients with mitral regurgitation (MR). Methods: This retrospective cohort study included 1,536 consecutive patients aged <65 years with moderate or severe chronic primary MR diagnosed between 2009 and 2018. The primary and secondary outcomes were all-cause and cardiovascular mortality, respectively. According to the current guidelines, the cut-off value of e' velocity was defined as 7 cm/s. Results: A total of 404 individuals were enrolled (median age, 51.0 years; 64.1% male; 47.8% severe MR). During a median 6.0-year follow-up, there were 40 all-cause mortality and 16 cardiovascular deaths. Multivariate analysis revealed a significant association between e' velocity and all-cause death (adjusted hazard ratio [aHR], 0.770; 95% confidence interval [CI], 0.634-0.935; p=0.008) and cardiovascular death (aHR, 0.690; 95% CI, 0.477-0.998; p=0.049). Abnormal e' velocity (≤7 cm/s) independently predicted all-cause death (aHR, 2.467; 95% CI, 1.170-5.200; p=0.018) and cardiovascular death (aHR, 5.021; 95% CI, 1.189-21.211; p=0.028), regardless of symptoms, LV dimension and ejection fraction. Subgroup analysis according to sex, MR severity, mitral valve replacement/repair, and symptoms, showed no significant interactions. Including e' velocity in the 10-year risk score improved reclassification for mortality (net reclassification improvement [NRI], 0.154; 95% CI, 0.308-0.910; p<0.001) and cardiovascular death (NRI, 1.018; 95% CI, 0.680-1.356; p<0.001). Conclusions: In patients aged <65 years with primary MR, e' velocity served as an independent predictor of all-cause and cardiovascular deaths.

• Radiation Oncology Journal
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• v.21 no.3
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• pp.216-221
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• 2003

Purpose: To investigate the modulation of radiosensitivity by celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, on cancer cells over- and under-expressing COX-2. Materials and Methods: A clonogenic radiation survival analysis was performed on A549 human lung and MCF-7 human breast cancer cell lines incubated in both 1 and $10\%$ fetal bovine serum (FBS) containing media. The apoptosis in both cell lines was measured after treatment with radiation and/or celecoxib. Results: Celecoxib enhanced the radiation sensitivity of the A549 cells in the medium containing the $10\%$ FBS, with radiation enhancement ratios of 1.58 and 1.81 respectively, at surviving fractions of 0.1, with $30\muM\;and\;50\muM$ celecoxib. This enhanced radiosensitivity disappeared in the medium containing the $1\%$ FBS. Celecoxib did not change the radiation sensitivity of the MCF-7 cells in either media. The induction of apoptosis by celecoxib and radiation was not synergistic in either cell line. Conclwsion: Celecoxib, a selective COX-2 inhibitor, preferentially enhanced the effect of radiation on COX-2 over-expressing cancer cells compared to the cells with a low expression, and this effect disappeared on incubation of the cells during drug treatment in the medium with suboptimal serum concentration. Apoptosis did not appear to be the underlying mechanism of this radiation enhancement effect due to celecoxib on the A549 cells. These findings suggest radiosensitization by a selective COX-2 inhibitor is COX-2 dependent.