• Title/Summary/Keyword: Synergic Effect

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Concentration-dependent in vitro Anti-osteoarthritis Effects of Mixed Formula - Pomegranate Concentrate Powder: Eucommiae Cortex: Achyranthis Radix 5:4:1 (g/g) on the Primary Cultured Rat Articular Chondrocytes

  • Choi, Beom Rak;Ku, Sae Kwang;Kang, Su Jin;Park, Hye Rim;Sung, Mi Sun;Lee, Young Joon;Park, Ki Moon
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.33 no.2
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    • pp.131-140
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    • 2019
  • The objective of present study is to evaluate concentration-dependent in vitro anti-osteoarthritic (OA) effects of synergic mixed formula consisted of dried pomegranate juice concentrate powder, Eucommiae Cortex aqueous extract and Achyranthis Radix aqueous extract 5:4:1 (g/g) mixture on the primary cultured rat articular chondrocytes. First, any cytotoxic effect of mixture was observed using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium Bromide) assay. Next, cyto-protective effect of test substances was evaluated by using the recombinant human interleukin $(rhIL)-1{\alpha}$ induced chondrocytes. In addition, anti-inflammatory effects were also observed on the lipopolysaccaride (LPS) treated chondrocytes through prostaglandin $E_2(PGE_2)$ productions and 5-lipoxygenase (LPO) activities, and inhibitory effects on matrix metalloproteinase (MMP)-2 and MMP-9 activities were observed on $rhIL-1{\alpha}$ treated chondrocytes with their extracellular matrix (ECM) related mRNA expressions. No obvious cytotoxic effects of mixture were demonstrated. Inflammatory damages of chondrocytes and related ECM degradations induced by treatment of LPS or $rhIL-1{\alpha}$ were significantly and concentration-dependently inhibited by pretreatment of mixture from a concentration level of 0.001 mg/ml to 1 mg/ml. In addition, mixture showed $IC_{50}$ for $rhIL-1{\alpha}-induced$ MMP-2 and MMP-9 activities as 44.01 and $162.47{\mu}g/ml$, and also showed $EC_{50}$ for $rhIL-1{\alpha}-induced$ inhibition of collagen type II, SOX9 and aggrecan mRNA expression as 8.61, 10.79 and $4.47{\mu}g/ml$, respectively. It is observed that mixture showed concentration-dependent anti-inflammatory and cytoprotective ECM preserved effects on the primary cultured rat articular chondrocytes without cytotoxicity.

Evaluation on Anti-fungal Activity and Synergy Effects of Essential Oil and Their Constituents from Abies holophylla (전나무 정유의 항진균 효과와 유효성분의 시너지효과 평가)

  • Kim, Seon-Hong;Lee, Su-Yeon;Cho, Seong-Min;Hong, Chang-Young;Park, Mi-Jin;Choi, In-Gyu
    • Journal of the Korean Wood Science and Technology
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    • v.44 no.1
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    • pp.113-123
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    • 2016
  • This study was to investigate the antifungal activity of A. holophylla essential oil against dermatophytes, such as Epidermophyton floccosum, Trichophyton mentagrophytes and Trichophyton rubrum, and to determine the potential effective compound as dermatitis treatment. To evaluate the potential antifungal activities of A. holophylla essential oil and its fractions, paper disc diffusion and agar dilution method tested with morphological observation. Also, their major constituents were analyzed by GC/MS. To determine synergic effects of active ingredient from A. holophylla essential oil were carried out by checkerboard microtiter plate testing. The morphological changes of the dermatophytes exposed to active fraction G4 were observed by electron microscopes. As the results, the highest activities were identified in the fraction containing ${\alpha}$-bisabolol. A mixture of ${\alpha}$-bisabolol and bornyl acetate showed the synergy effects, expressing high potential effects. Also, morphological observation using electron microscopes showed a dramatic changes of cell membrane of E. floccosum and T. rubrum exposed to fraction G4 containing ${\alpha}$-bisabolol. In conclusion, A. holophylla essential oil and its constituents were expected to be used as antifungal agent or raw material for dermatitis therapy.

Candida magnoliae에 의한 erythritol 생산을 위한 유가식 공정의 개발

  • Park, Chang-Yeol;Seo, Jin-Ho;Yu, Yeon-U
    • 한국생물공학회:학술대회논문집
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    • 2000.04a
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    • pp.53-56
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    • 2000
  • Two-stage fed-batch culture was peformed to improve the volumetric productivity of erythritol. In the growth phase dissolved oxygen was maintained to 20% and the feed medium was automatically supplied to the fermenter by pH-stat mode. The cell yield was 0.76 g-cell/g-glucose. In two-stage fed-batch culture, 41% of total erythritol conversion yield with 187 g/L of erythritol concentration and 2.79 g/L-h of maximum erythritol Productivity were obtained when 400 g/L of glucose was directly added in the form of non-sterile powder at production phase. The erythritol productivity increased in parallel with cell mass. The metabolic shift in the biosynthetic pathway of erythritol was caused by dissolved oxygen concentration. The production of gluconic acid was observed when the dissolved oxygen in the medium was maintained over 40% during the production phase, whereas the dissolved oxygen concentration lower than 40% caused the production of citric acid. But the butyric acid was produced independently with dissolved oxygen concentration in the medium. The production of organic acids such as gluconic acid, citric acid, and butyric acid was decreased by addition of mineral salts.

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Immuno-Regulatory Activities of an Isoflavone Glycoside, 4', $6-Dimethoxylsoflavone-7-O-{\beta}-D-Glucopyranoside$ and the Crude Extract Isolated from Amorpha fruticosa LINNE

  • Kim, Jung-Hwa;Kim, Cheol-Hee;Kwon, Min-Cheol;Kim, Hyou-Sung;Lee, Kang-Yoon;Lee, Hyun-Jung;Kang, Ha-Young;Lee, Hak-Ju;Lee, Hyeon-Yong
    • Korean Journal of Medicinal Crop Science
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    • v.14 no.2
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    • pp.63-69
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    • 2006
  • The methanolic (MeOH) extract of A. fruticosa bark, which showed immune-regulatory activities, was separated to purify an active compared by means of a multi-stage column chromatography. This resulted in the isolation and characterization of an isoflavone glycoside named 4', $6-Dimethoxyisoflavone-7-O-{\beta}-D-glucopyranoside$. Immuno-regulatory activities of the crude extract of Amorpha fruticosa LINNE bark were compared with that of an isoflavone glycoside (4', $6-dimethoxyisoflavone-7-O-{\beta}-D-glucopyranoside$). The crude methanolic extract of A. fruticosa and purified single compound showed 16% of relatively low cytotoxicity at a maximum concentration of 1.0 g/L in cultivated normal human lung cell line (HEL299). Cell growth of human T cells was increased up to 15%, 0.5 g/L of the crude extract added group. This was higher than a single compound added one. On the other hand, specific production rates of IL-6 and $TNF-{\alpha}$ from T cell were higher in the purified compound treat group ($0.82{\times}10^{-4}\;pg/cell$ and $1.08{\times}10^{-4}\;pg/cell$, respectively), compared to 0.5 g/L of the crude extract added group ($0.65{\times}10^{-4}\;pg/cell$ and $0.84{\times}10^{-4}\;pg/cell$, respectively). In addition, the growth of NK-92MI cells incubated with the crude extract was higher up to 56% over the cells grown with a single compound (0.5 g/L). In overall, the crude extract showed relatively higher immuno-regulatory activities compared with a single compound, probably due to the synergic effect given by other substances existed in the crude extract. Even though the siolated compound stimulated higher secretion of cytokines from human T cells.

Synergic induction of human periodontal ligament fibroblast cell death by nitric oxide and N-methyl-D-aspartic acid receptor antagonist

  • Seo, Tae-Gun;Cha, Se-Ho;Woo, Kyung-Mi;Park, Yun-Soo;Cho, Yun-Mi;Lee, Jeong-Soon;Kim, Tae-Il
    • Journal of Periodontal and Implant Science
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    • v.41 no.1
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    • pp.17-22
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    • 2011
  • Purpose: Nitric oxide (NO) has been known as an important regulator of osteoblasts and periodontal ligament cell activity. This study was performed to investigate the relationship between NO-mediated cell death of human periodontal ligament fibroblasts (PDLFs) and N-methyl-D-aspartic acid (NMDA) receptor antagonist (+)-5-methyl-10, 11-dihydro-5H-dibenzo[a,d]cyclohepten-5, 10-imine hydrogen maleate (MK801). Methods: Human PDLFs were treated with various concentrations (0 to 4 mM) of sodium nitroprusside (SNP) with or without $200\;{\mu}M$ MK801 in culture media for 16 hours and the cell medium was then removed and replaced by fresh medium containing MTS reagent for cell proliferation assay. Western blot analysis was performed to investigate the effects of SNP on the expression of Bax, cytochrome c, and caspase-3 proteins. The differences for each value among the sample groups were compared using analysis of variance with 95% confidence intervals. Results: In the case of SNP treatment, as a NO donor, cell viability was significantly decreased in a concentration-dependent manner. In addition, a synergistic effect was shown when both SNP and NMDA receptor antagonist was added to the medium. SNP treated PDLFs exhibited a round shape in culture conditions and were dramatically reduced in cell number. SNP treatment also increased levels of apoptotic marker protein, such as Bax and cytochrome c, and reduced caspase-3 in PDLFs. Mitogen-activated protein kinase signaling was activated by treatment of SNP and NMDA receptor antagonist. Conclusions: These results suggest that excessive production of NO may induce apoptosis and that NMDA receptor may modulate NO-induced apoptosis in PDLFs.

Effect of Jaeumkanghwatang (JEKHT), a Polyherbal Formula on the Pharmacokinetics Profiles of Tamoxifen in Male SD Rats (2) - Oral Combination Treatment of Tamoxifen 50 mg/kg with JEKHT 100 mg/kg on JEKHT 6-day Repeated Pretreated Rats with 8-day Repeated Co-administration -

  • Park, Soo Jin;Kwak, Min A;Park, Sung Hwan;Lee, Young Joon;Ku, Sae Kwang
    • Journal of Society of Preventive Korean Medicine
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    • v.20 no.2
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    • pp.97-109
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    • 2016
  • Objectives : The effects of Jaeumkanghwatang (JEKHT) co-administration on the pharmacokinetics of tamoxifen were observed after oral combination treatment of tamoxifen 50 mg/kg with JEKHT 100 mg/kg on JEKHT 6-day repeated oral pretreated rats with 8-day repeated co-administration to confirm the effects of JEKHT co-administration on the pharmacokinetics of tamoxifen. Methods : Six days after pretreatment of JEKHT 100 mg/kg, tamoxifen 50 mg/kg was co-administered with JEKHT 100 mg/kg, once a day for 8 days within 5 min. The blood were collected at 30 min before administration, 30 min, 1, 2, 3, 4, 6, 8 and 24 hrs after end of first and last 8th tamoxifen treatment, and plasma concentrations of tamoxifen were analyzed using LC-MS/MS methods. PK parameters of tamoxifen ($T_{max}$, $C_{max}$, AUC, $t_{1/2}$ and $MRT_{inf}$) were analysis as compared with tamoxifen single administered. Results : Six-day repeated oral pretreatment of JEKHT and 8-day repeated oral co-administration of tamoxifen within 5 min did not influenced on the plasma concentrations and pharmacokinetic parameters of tamoxifen, oral bioavailability, as compared with tamoxifen single treated rats, except for some negligible effects. Conclusions : It is concluded that JEKHT did not influenced on the plasma concentrations and pharmacokinetic parameters, the oral bioavailability of tamoxifen. Therefore, it is considered that co-administration of JEKHT and tamoxifen will be provide an effective novel treatment regimen on the comprehensive and integrative medicine for breast cancer patients, if they showed favorable synergic effects on the pharmacodynamics or reduce the tamoxifen treatment related toxicity and side effects in future studies.

Effect of Gongjindan, a Traditional Korean Polyherbal Formula, on the Pharmacokinetics Profiles of Donepezil in Male SDRats (2) - Single Oral Combination Treatment of Donepezil 10mg/kg with Gongjindan 100mg/kg, 1.5hr-intervals with 7-day Repeated Treatment -

  • Kwon, Oh Dae;Chung, Dae-Kyoo;Park, Soo Jin;Lee, Young Joon;Ku, Sae Kwang
    • Journal of Society of Preventive Korean Medicine
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    • v.17 no.2
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    • pp.139-155
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    • 2013
  • Purpose : This study was aim to evaluate effects of pharmacodynamics and toxicity in combination therapy of donepezil with Gongjindan. The effects of Gongjindan co-administration on the pharmacokinetics (PK) of donepezil were observed after single and 7-day repeated oral co-administration with 1.5hr-intervals, to evaluate synergic pharmacodynamics and reduce toxicity of combination therapy of donepezil with Gongjindan. Materials and Methods : After 10mg/kg of donepezil treatment, Gongjindan100mg/kg was administered with 1.5hr-intervals. The plasma were collected at 30min before administration, 30min, 1, 2, 3, 4, 6, 8 and 24hrs after end of first and last 7th donepezil treatment, and plasma concentrations of donepezil were analyzed using LC-MS/MS methods. Results : Gongjindan markedly inhibited the absorption of donepezilregardless of sample time, from 30min to 8hrs after end of first 1.5hr-interval co-administration as compared with donepezil single treated rats. Especially the absorption of donepezil was significantly decreased at 2, 4, 6 and 8hrs after co-administration as compared with donepezilsingle treated rats. Accordingly, the Cmax (-26.236%), $AUC_{0-t}$(-26.02%) and $AUC_{0-inf}$(-25.90%) of donepezil in 1.5hr-interval co-administered rats were dramatically decreased as compared with donepezilsingle treated rats, respectively. However, no meaningful changes on the plasma donepezil concentrations and pharmacokinetic parameters were detected after end of last 7th 1.5hr-interval co-administration as compared with donerezil single treated rats, except for non-significant slight increases of Tmax(16.67%) detected in co-administered rats as compared with donepezil single treated rats. Conclusion : These findings are considered as direct evidences that Gongjindan also decreased oral bioavailability of donerezil as inhibited the absorptions, when they were co-administered with 1.5hr-intervals, but they may be adapted after 7 days continuous repeated l.5hr-interval co-administration.

Rheological Behavior of Semi-Solid Ointment Base (Vaseline) in Steady Shear Flow Fields (정상전단유동장에서 반고형 연고기제(바셀린)의 레올로지 거동)

  • Song, Ki-Won;Kim, Yoon-Jeong;Lee, Chi-Ho
    • Journal of Pharmaceutical Investigation
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    • v.37 no.3
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    • pp.137-148
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    • 2007
  • Using a strain-controlled rheometer [Rheometrics Dynamic Analyzer (RDA II)], the steady shear flow properties of a semi-solid ointment base (vaseline) have been measured over a wide range of shear rates at temperature range of $25{\sim}60^{\circ}C$. In this article, the steady shear flow properties (shear stress, steady shear viscosity and yield stress) were reported from the experimentally obtained data and the effects of shear rate as well as temperature on these properties were discussed in detail. In addition, several inelastic-viscoplastic flow models including a yield stress parameter were employed to make a quantitative evaluation of the steady shear flow behavior, and then the applicability of these models was examined by calculating the various material parameters (yield stress, consistency index and flow behavior index). Main findings obtained from this study can be summarized as follows : (1) At temperature range lower than $40^{\circ}C$, vaseline is regarded as a viscoplastic material having a finite magnitude of yield stress and its flow behavior beyond a yield stress shows a shear-thinning (or pseudo-plastic) feature, indicating a decrease in steady shear viscosity as an increase in shear rate. At this temperature range, the flow curve of vaseline has two inflection points and the first inflection point occurring at relatively lower shear rate corresponds to a static yield stress. The static yield stress of vaseline is decreased with increasing temperature and takes place at a lower shear rate, due to a progressive breakdown of three dimensional network structure. (2) At temperature range higher than $45^{\circ}C$, vaseline becomes a viscous liquid with no yield stress and its flow character exhibits a Newtonian behavior, demonstrating a constant steady shear viscosity regardless of an increase in shear rate. With increasing temperature, vaseline begins to show a Newtonian behavior at a lower shear rate range, indicating that the microcrystalline structure is completely destroyed due to a synergic effect of high temperature and shear deformation. (3) Over a whole range of temperatures tested, the Herschel-Bulkley, Mizrahi-Berk, and Heinz-Casson models are all applicable and have an almostly equivalent ability to quantitatively describe the steady shear flow behavior of vaseline, whereas the Bingham, Casson,and Vocadlo models do not give a good ability.

Combination of an Enzymatically Hydrolyzed Yeast and Yeast Culture with a Direct-fed Microbial in the Feeds of Broiler Chickens

  • Gomez, S.;Angeles, M.L.;Mojica, M.C.;Jalukar, S.
    • Asian-Australasian Journal of Animal Sciences
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    • v.25 no.5
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    • pp.665-673
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    • 2012
  • A balance trial experiment was carried out to evaluate the potential relationship between an enzymatically hydrolyzed yeast (EHY) and yeast culture combined with a live Bacillus subtilis (Bs) on the productive parameters, ileal digestibility, retention of nutrient and energy and villus morphology in broilers. Seventy two 28 d old, Ross B308 male broilers were assigned to a factorial combination of 2 levels of EHY (0 and 1 kg/ton of feed) and 2 levels of Bs (0 and 125 g/ton of feed). The experiment lasted 2 weeks. Several treatment interactions were observed. EHY-fed broilers showed the lowest feed intake and feed conversion ratio whereas Bs-fed broilers showed the highest feed intake and intermediate feed conversion ratio (EHY and BS interaction, p<0.05). Also, EHY-fed broilers had greater ileal digestibility of dry matter (EHY and BS interaction, p<0.01) and energy (EHY and BS interaction, p<0.05) but these responses were counterbalanced by the combination of EHY and Bs. The thickness of the mucosa was similar between the control and EHY-fed broilers, but was lowest when Bs was added alone (EHY and BS interaction, p<0.01). The thickness of the villus was greater in EHY plus Bs-fed broilers, intermediate for the control and lower for Bs or EHY-fed broilers (EHY and BS interaction, p<0.05). The area of the villus was greater in the control and EHY plus Bs-fed broilers (EHY and BS interaction, p<0.05). In addition, EHY-fed broilers showed greater breast yield and nitrogen retention (p<0.01) and ashes digestibility (p<0.05). On the other hand, Bs-fed broilers had greater carcass and breast weight, nitrogen retention, energy excretion and villus height (p<0.05). In summary, EHY and Bs enhanced some growth, carcass and nutrient retention responses, but did not show any synergic relationship in these responses. Opposite to this, the results suggest that the positive effect of EHY on the feed conversion and digestibility of nutrients were counterbalanced by the addition of Bs.

A Study of Hexavalent Chromium Reduction by Iron Sulfide (황화철에 의한 6가 크롬의 환원에 관한 연구)

  • Jo, Se-I;Park, Jae-Woo
    • Journal of Korean Society of Environmental Engineers
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    • v.27 no.6
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    • pp.657-662
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    • 2005
  • Iron sulfide(FeS) is significantly produced through both abiotic and biotic processes in natural sediments and pore waters. In this study, chromium(VI) reaction with iron sulfide at various initial concentrations and at pH values of 4 and 8 was conducted to better understand the interactions between Cr(VI) and Fe(II) species dissolved from iron sulfide in both the aqueous and solid phases. Also, the removal efficiency of iron sulfide was compared with zero valent iron and other iron bearing oxides such as ${\alpha}-Fe_2O_3$, ${\alpha}-FeOOH$ and $Fe_3O_4$. The Cr(VI) removal rate by iron sulfide was higher at pH 4 than at pH 8 because more dissolved Fe(II) existed at pH 4 than at pH 8. Chromium and iron(oxyhydroxide) could be identified on the iron sulfide surface with transmission microscopy imaging and energy dispersive spectroscopy. The removal capacity of iron sulfide was much higher than zero valent iron and other iron oxide minerals due to the synergic effect of hydrogen sulfide and ferrous iron.