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Mechanism of Panax notoginseng saponins modulation of miR-214-3p/NR1I3 affecting the pharmacodynamics and pharmacokinetics of warfarin

  • Yuting Yang;Zhenyu Zhai;Huiming Yao;Ling He;Jun Shao;Zirong Xia;Juxiang Li
    • Journal of Ginseng Research
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    • v.48 no.5
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    • pp.494-503
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    • 2024
  • Background: With the prevalence of dietary supplements, the use of combinations of herbs and drugs is gradually increasing, together with the risk of drug interactions. In our clinical work, we unexpectedly found that the combination of Panax notoginseng and warfarin, which are herbs that activate blood circulation and remove blood stasis, showed antagonistic effects instead. The purpose of this study was to evaluate the drug interaction between Panax notoginseng saponins (PNS) and warfarin, the main active ingredient of Panax notoginseng, and to explore the interaction mechanism. Methods: The effects and mechanisms of PNS on the pharmacodynamics and pharmacokinetics of warfarin were explored mainly in Sprague-Dawley rats and HepG2 cells. Elisa was used to detect the concentrations of coagulation factors, HPLC-MS to detect the blood concentrations of warfarin in rats, immunoblotting was employed to examine protein levels, qRT-PCR to detect mRNA levels, cellular immunofluorescence to detect the localization of NR1I3, and dual luciferase to verify the binding of miR-214-3p and NR1I3. Results: PNS significantly accelerated warfarin metabolism and reduced its efficacy, accompanied by increased expression of NR1I3 and CYP2C9. Interference with NR1I3 rescued the accelerated metabolism of warfarin induce by PNS co-administration. In addition, we demonstrated that PNS significantly reduced miR-214-3p expression, whereas miR-214-3p overexpression reduced NR1I3 and CYP2C9 expression, resulting in a weakened antagonistic effect of PNS on warfarin. Additionally, we found that miR-214-3p bound directly to NR1I3 3'-UTR and significantly downregulated NR1I3 expression. Conclusion: Our study demonstrated that PNS accelerates warfarin metabolism and reduces its pharmacodynamics by downregulating miR-214-3p, leading to increased expression of its target gene NR1I3, these findings provide new insights for clinical drug applications to avoid adverse effects.

Isolation of Isoflavones and Soyasaponins from the Germ of Soybean (콩 배아로 부터 Isoflavone과 Soyasaponin의 동시 분리)

  • Kim, Sun-Lim;Lee, Jae-Eun;Kim, Yul-Ho;Jung, Gun-Ho;Kim, Dea-Wook;Lee, Choon-Ki;Kim, Mi-Jung;Kim, Jung-Tae;Lee, Yu-Young;Hwang, Tae-Young;Lee, Kwang-Sik;Kim, Wook-Han;Kwon, Young-Up;Kim, Hong-Sig;Chung, Ill-Min
    • KOREAN JOURNAL OF CROP SCIENCE
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    • v.58 no.2
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    • pp.149-160
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    • 2013
  • The objective of present study was to simultaneously isolate of isoflavone and soyasaponin compounds from the germ of soybean seeds. Soy germ flours were defatted with hexane for 48h at room temperature, and methanolic extracts were prepared using reflux apparatus at $90^{\circ}C$ for 6h, two times. After extraction, extracts were separated with preparative RP-$C_{18}$ packing column ($125{\AA}$, $55-105{\mu}m$, $40{\times}150mm$), and collected 52 fractions were identified with TLC plate (Kieselgel 60 F-254) and HPLC, respectively. Among the identified isoflavone and soyasaponin fractions, isoflavone fractions were re-separated using a recycling HPLC with gel permeation column (Jaigel-W252, $20{\times}500mm$). Final fractions were air-dried, and the purified compounds of two isoflavones (ISF-1-1, ISF-1-2) and four soyasaponins (SAP-1, SAP-2, SAP-3, SAP-4) were obtained. Two isoflavone compounds (ISF-1-1, ISF-1-2) were acid-hydrolyzed for the identification of their aglycones, and confirmed by comparing with 12 types of isoflavone isomers. While the four kinds of soyasaponins were identified by using a micro Q-TOF mass spectrometer in the ESI positive mode with capillary voltage of 4.5kV, and dry temperature of $200^{\circ}C$. Base on the obtained results, it was conclude that ISF-1-1 is the mixture isomers of daidzin (43.4%), glycitin (47.0%), and genistin (9.6%), but ISF-1-2 is the single compound of genistin (99.8% <). On the other hand, soyasaponin SAP-1 is the mixture compounds of soyasaponin A-group (Aa, Ab, Ac, Ae, Af); SAP-2 is soyasaponin B-group (Ba, Bb, Bc) and E-group (Bd, Be); SAP-3 is soyasaponin B-group (Ba, Bb, Bc), E-group (Bd, Be), and DDMP-group (${\beta}g$); SAP-4 is soyasaponin B-group (Ba, Bb, Bc), E-group (Bd, Be), and DDMP-group (${\beta}g$, ${\beta}a$), respectively.

Sorption Efficiency of the Bamboo Charcoal to Remove the Cesium in the Contaminated Water System (오염수계 내 세슘 제거를 위한 대나무 활성탄의 흡착효율 규명)

  • Ahn, Joungpil;Lee, Minhee
    • Economic and Environmental Geology
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    • v.51 no.2
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    • pp.87-97
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    • 2018
  • The cesium (Cs) removal from the contaminated water system has been considered to be difficult because the cesium likes to exist as soluble phases such as ion and complexes than the solid in water system. Many researches have focused on developing the breakthrough adsorbent to increase the cesium removal efficiency in water. In this study, the laboratory scale experiments were performed to investigate the feasibility of the adsorption process using the bamboo charcoal for the Cs contaminated water system. The Cs removal efficiency of the bamboo charcoal were measured and the optimal adsorption conditions were determined by the adsorption batch experiments. Total 5 types of commercialized bamboo charcoals in Korea were used to identify their surface properties from SEM-EDS and XRD analyses and 3 types of bamboo charcoals having large specific surface areas were used for the adsorption batch experiment. The batch experiments to calculate the Cs removal efficiency were performed at conditions of various Cs concentration (0.01 - 10 mg/L), pH (3 - 11), temperature ($5-30^{\circ}C$), and adsorption time (10 - 120 min.). Experimental results were fitted to the Langmuir adsorption isotherm curve and their adsorption constants were determined to understand the adsorption properties of bamboo charcoal for Cs contaminated water system. From results of SEM-EDS analyses, the surfaces of bamboo charcoal particles were composed of typical fiber structures having various pores and dense lamella structures in supporting major adsorption spaces for Cs. From results of adsorption batch experiments, the Cs-133 removal efficiency of C type bamboo charcoal was the highest among those of 3 bamboo charcoal types and it was higher than 75 % (maximum of 82 %) even when the initial Cs concentration in water was lower than 1.0 mg/L, suggesting that the adsorption process using the bamboo charcoal has a great potential to remove Cs from the genuine Cs contaminated water, of which Cs concentration is low (< 1.0 mg/L) in general. The high Cs removal efficiency of bamboo charcoal was maintained in a relatively wide range of temperatures and pHs, supporting that the usage of the bamboo charcoal is feasible for various types of water. Experimental results were similar to the Langmuir adsorption model and the maximum amount of Cs adsorption (qm:mg/g) was 63.4 mg/g, which was higher than those of commercialized adsorbents used in previous studies. The surface coverage (${\theta}$) of bamboo charcoal was also maintained in low when the Cs concentration in water was < 1.0 mg/L, investigating that the Cs contaminated water can be remediated up with a small amount of bamboo charcoal.

The Comparison of Existing Synthetic Unit Hydrograph Method in Korea (국내 기존 합성단위도 방법의 비교)

  • Jeong, Seong-Won;Mun, Jang-Won
    • Journal of Korea Water Resources Association
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    • v.34 no.6
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    • pp.659-672
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    • 2001
  • Generally, design flood for a hydraulic structure is estimated using statistical analysis of runoff data. However, due to the lack of runoff data, it is difficult that the statistical method is applied for estimation of design flood. In this case, the synthetic unit hydrograph method is used generally and the models such as NYMO method, Snyder method, SCS method, and HYMO method have been widely used in Korea. In this study, these methods and KICT method, which is developed in year 2000, are compared and analyzed in 10 study areas. Firstly, peak flow and peak time of representative unit hydrograph and synthetic unit hydrograph in study area are compared, and secondly, the shape of unit hydrograph is compared using a root mean square error(RMSE). In Nakayasu method developed in Japan, synthetic unit hydrograph is very different from peak flow, peak time, and the shape of representative unit hydrograph, and KICT method(2000) is superior to others. Also, KICT method(2000) is superior to others in the aspects of using hydrologic and topographical data. Therefore, Nakayasu method is not a proper in hydrological practice. Moreover, it is considered that KICT model is a better method for the estimation of design flood. However, if other model, i.e. SCS method, Nakayasu method, and HYMO method, is used, parameters or regression equations must be adjusted by analysis of real data in Korea.

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Velocity-effective stress response of $CO_2$-saturated sandstones ($CO_2$로 포화된 사암의 속도-유효응력 반응)

  • Siggins, Anthony F.
    • Geophysics and Geophysical Exploration
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    • v.9 no.1
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    • pp.60-66
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    • 2006
  • Three differing sandstones, two synthetic and one field sample, have been tested ultrasonically under a range of confining pressures and pore pressures representative of in-situ reservoir pressures. These sandstones include: a synthetic sandstone with calcite intergranular cement produced using the CSIRO Calcite In-situ Precipitation Process (CIPS); a synthetic sandstone with silica intergranular cement; and a core sample from the Otway Basin Waarre Formation, Boggy Creek 1 well, from the target lithology for a trial $CO_2$ pilot project. Initial testing was carried on the cores at "room-dried" conditions, with confining pressures up to 65 MPa in steps of 5 MPa. All cores were then flooded with $CO_2$, initially in the gas phase at 6 MPa, $22^{\circ}C$, then with liquid-phase $CO_2$ at a temperature of $22^{\circ}C$ and pressures from 7 MPa to 17 MPa in steps of 5 MPa. Confining pressures varied from 10 MPa to 65 MPa. Ultrasonic waveforms for both P- and S-waves were recorded at each effective pressure increment. Velocity versus effective pressure responses were calculated from the experimental data for both P- and S-waves. Attenuations $(1/Q_p)$ were calculated from the waveform data using spectral ratio methods. Theoretical calculations of velocity as a function of effective pressure for each sandstone were made using the $CO_2$ pressure-density and $CO_2$ bulk modulus-pressure phase diagrams and Gassmann effective medium theory. Flooding the cores with gaseous phase $CO_2$ produced negligible change in velocity-effective stress relationships compared to the dry state (air saturated). Flooding with liquid-phase $CO_2$ at various pore pressures lowered velocities by approximately 8% on average compared to the air-saturated state. Attenuations increased with liquid-phase $CO_2$ flooding compared to the air-saturated case. Experimental data agreed with the Gassmann calculations at high effective pressures. The "critical" effective pressure, at which agreement with theory occurred, varied with sandstone type. Discrepancies are thought to be due to differing micro-crack populations in the microstructure of each sandstone type. The agreement with theory at high effective pressures is significant and gives some confidence in predicting seismic behaviour under field conditions when $CO_2$ is injected.

Characterization of Pretreatment for Barley straw by Alkaline Solutions (염기 용매를 이용한 보릿짚의 전처리 특성)

  • Kim, Kyoung-Seob;Kim, Jun Seok
    • Korean Chemical Engineering Research
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    • v.50 no.1
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    • pp.18-24
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    • 2012
  • Lignocellulose is difficult to hydrolyze due to the presence of lignin and the technology developed for cellulose fermentation to ethanol is not yet economically viable. However, recent advances in the extremely new field of biotechnology for the ethanol production are making it possible to use of Agriculture residual biomass, e.q., Barley straw, because of their several superior aspects as Agriculture residual biomass; low lignin, high contents of carbohydrates. Barley straw consists of 39.78% cellulose (glucose), 22.56% hemicelluloses and 19.27% lignin. Pretreatment of barley straw using NaOH pretreatment solutions concentration with 2%, temperature $85^{\circ}C$ and reaction times 1 hr were investigates. $NH_4OH$ pretreatment condition was solutions concentration with 15%, temperature $60^{\circ}C$, and reaction times 24hr were investigates. Furthermore, enzymatic saccharification using cellulose at $50^{\circ}C$, pH 4.8, 180 rpm for conversion of cellulose contained in barley straw to monomeric sugar. The pretreatment of barley straw using NaOH and $NH_4OH$ can significantly improve enzymatic saccharification of barley straw by extract more lignin and increasing its accessibility to hydrolytic enzymes. The result showed NaOH pretreatment extracted yield of lignin was 24.15%. $NH_4OH$ pretreatment extracted yield of lignin was 29.09%. Shaccharification of barley straw pretreatment by NaOH for 72hr and pH 4.8 result in maximum glucose concentration 15.39g/L (58.40%) and by $NH_4OH$ for 72hr and pH 4.8 result in maximum glucose concentration 16.01g/L (64.78%).

Identification and Characterization of Lactobacillus salivarius subsp. salivarius from Korean Feces

  • Bae, Hyoung-Churl
    • Proceedings of the Korean Society for Food Science of Animal Resources Conference
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    • 2004.05a
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    • pp.89-119
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    • 2004
  • This study was conducted to isolate lactobacilli having probiotic characteristics to be used as health adjuncts with fermented milk products. Acid tolerant strains were selected in Lactobacilli MRS broth adjusted to pH 4.0 from 80 healthy persons (infants, children and adults). And bile tolerant strains were examined in Lactobacilli MRS broth in which 1.0% bile salt was added. By estimation above characteristics, the strains No. 27, which was isolated from adult feces, was selected and identified as Lactobacillus salivarius subsp. salivarius based on carbohydrate fermentation and 16S rDNA sequencing. It was used as a probiotic strain in fermented milk products. The pH of fermented milk decreased from pH 6.7 to 5.0 and titratable acidity increased from 0.3% to 1.0% by L. salivarius subsp. salivarius (isolation strain 20, 35, and 37), when incubated for 36 h at $37^{\circ}C$. The number of viable cell counts of fermented milk was maximized at this incubation condition. The SDS-PAGE evidenced no significant change of casein but distinct changes of whey protein were observed by isolated L. salivarius subsp. salivarius for titratable acidity being incubated by $0.9{\sim}1.0%$ at $37^{\circ}C$. All of the strains produced 83.43 to 131.96 mM of lactic acid and 5.39 to 26.85 mM of isobutyric acid in fermented products. The in vitro culture experiment was performed to evaluate ability to reduce cholesterol levels and antimicrobial activity in the growth medium. The selected L. salivarius subsp. salivarius reduced $23{\sim}38%$ of cholesterol content in lactobacilli MRS broth during bacterial growth for 24 hours at $37^{\circ}C$. All of the isolated L. salivarius subsp. salivarius had an excellent antibacterial activity with $15{\sim}25$ mm of inhibition zone to E. coli KCTC1039, S. enteritidis KCCM3313, S. typhimurium M-15, and S. typhimurium KCCM40253 when its pH had not been adjusted. Also, all of the isolated L. salivarius subsp. salivarius had partial inhibition zone to E. coli KCTC1039, E. coli KCTC0115 and S. enteritidis KCCM3313 when it had been adjusted to pH 5.7. The selected strains were determined to have resistances of twelve antibiotic. Strains 27 and 35 among the L. salivarius subsp. salivarius showed the highest resistance to the antibiotics. Purified ${\alpha}$-galactosidase was obtained by DEAE-Sephadex A-50 ion exchange chromatography, Mono-Q ion exchange chromatography and HPLC column chromatography from L. salivarius subsp. salivarius 27. The specific activity of the purified enzyme was 8,994 units/mg protein, representing an 17.09 folds purification of the original cell crude extract. The molecular weight of enzyme was identified about 53,000 dalton by 12% SDS-PAGE. Optimal temperature and pH for activity of this enzyme were $40^{\circ}C$ and 7.0 respectively. The enzyme was found to be stable between 25 and $50^{\circ}C$. ${\alpha}$-galactosidase activity was lost rapidly below pH 5.0 and above pH 9.0. This enzyme was liberated galactose from melibiose, raffinose, and stachyose, and also the hydrolysis rate of substrate was compound by HPLC. These results indicated that some of the L. salivarius subsp. salivarius (strain 27 and 35) are considered as effective probiotic strains with a potential for industrial applications, but the further study is needed to establish their use as probiotics in vivo.

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Influence of Land Cover Map and Its Vegetation Emission Factor on Ozone Concentration Simulation (토지피복 지도와 식생 배출계수가 오존농도 모의에 미치는 영향)

  • Kyeongsu Kim;Seung-Jae Lee
    • Korean Journal of Agricultural and Forest Meteorology
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    • v.25 no.1
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    • pp.48-59
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    • 2023
  • Ground-level ozone affects human health and plant growth. Ozone is produced by chemical reactions between oxides of nitrogen (NOx) and volatile organic compounds (VOCs) from anthropogenic and biogenic sources. In this study, two different land cover and emission factor datasets were input to the MEGAN v2.1 emission model to examine how these parameters contribute to the biogenic emissions and ozone production. Four input sensitivity scenarios (A, B, C and D) were generated from land cover and vegetation emission factors combination. The effects of BVOCs emissions by scenario were also investigated. From air quality modeling result using CAMx, maximum 1 hour ozone concentrations were estimated 62 ppb, 60 ppb, 68 ppb, 65 ppb, 55 ppb for scenarios A, B, C, D and E, respectively. For maximum 8 hour ozone concentration, 57 ppb, 56 ppb, 63 ppb, 60 ppb, and 53 ppb were estimated by scenario. The minimum difference by land cover was up to 25 ppb and by emission factor that was up to 35 ppb. From the modeling performance evaluation using ground ozone measurement over the six regions (East Seoul, West Seoul, Incheon, Namyangju, Wonju, and Daegu), the model performed well in terms of the correlation coefficient (0.6 to 0.82). For the 4 urban regions (East Seoul, West Seoul, Incheon, and Namyangju), ozone simulations were not quite sensitive to the change of BVOC emissions. For rural regions (Wonju and Daegu) , however, BVOC emission affected ozone concentration much more than previously mentioned regions, especially in case of scenario C. This implies the importance of biogenic emissions on ozone production over the sub-urban to rural regions.

Isotopic Determination of Food Sources of Benthic Invertebrates in Two Different Macroalgal Habitats in the Korean Coasts (동위원소 분석에 의한 동해와 남해 연안의 상이한 해조류 군락에 서식하는 저서무척추동물 먹이원 평가)

  • Kang, Chang-Keun;Choy, Eun-Jung;Song, Haeng-Seop;Park, Hyun-Je;Soe, In-Soo;Jo, Q-Tae;Lee, Kun-Seop
    • The Sea:JOURNAL OF THE KOREAN SOCIETY OF OCEANOGRAPHY
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    • v.12 no.4
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    • pp.380-389
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    • 2007
  • Stable carbon and nitrogen isotopes were analyzed in suspended particulate organic matter, macroalgae and macrobenthic invertebrates in order to determine the importance of primary organic matter sources in supporting food webs of rocky subtidal and intertidal macroalgal beds in the Korean coasts. Investigations were conducted at the inter tidal sites within Gwangyang bay, a semi-enclosed and eutrophicated bay, and the subtidal sites of the east coast, a relatively oligotrophic and open environment, in May and June 2005. Water-column suspension feeders showed more negative $\delta^{13}C$ values than those of the other feeding guilds, indicating trophic linkage with phytoplankton and thereby association with pelagic food chains. In contrast, animals of the other feeding guilds, including interface suspension feeders, herbivores, deposit feeders, omnivores and predators, displayed relatively less negative $\delta^{13}C$ values than those of the water-column suspension feeders and similar with that of macroalgae, indicating exclusive use of macroalgae-derived organic matter and association with benthic food chains. Most the macrobenthic species were considered to form strong trophic links with benthic food chains. In addition, the distribution of higher $\delta^{15}N$ values in macrobenthic consumers and macroalgae at the intertidal sites of Gwangyang Bay than those at the subtidal sites of the east coast suggests that anthropogenic nutrients may enhance the macroalgal production at the intertidal sites and in turn be incorporated into the particular littoral food web in Gwangyag Bay. These results confirm the dominant role of macroalgae in supporting rocky subtidal and intertidal food webs in the Korean coasts.

Comparison of Naphthalene Degradation Efficiency and OH Radical Production by the Change of Frequency and Reaction Conditions of Ultrasound (초음파 주파수 및 반응조건 변화에 따른 나프탈렌 분해효율과 OH 라디칼의 발생량 비교)

  • Park, Jong-Sung;Park, So-Young;Oh, Je-Ill;Jeong, Sang-Jo;Lee, Min-Ju;Her, Nam-Guk
    • Journal of Korean Society of Environmental Engineers
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    • v.31 no.2
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    • pp.79-89
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    • 2009
  • Naphthalene is a volatile, hydrophobic, and possibly carcinogenic compound that is known to have a severe detrimental effect to aquatic ecosystem. Our research examined the effects of various operating conditions (temperature, pH, initial concentration, and frequency and type of ultrasound) on the sonochemical degradation of naphthalene and OH radical production. The MDL (Method detection limit) determined by LC/FLD (1200 series, Agilient) using C-18 reversed column is measured up to 0.01 ppm. Naphthalene vapor produced from ultrasound irradiation was detected under 0.05 ppm. Comparison of naphthalene sonodegradion efficiency tested under open and closed reactor cover fell within less than 1% of difference. Increasing the reaction temperature from $15^{\circ}C$ to $40^{\circ}C$ resulted in reduction of naphthalene degradation efficiency ($15^{\circ}C$: 95% ${\rightarrow}$ $40^{\circ}C$: 85%), and altering pH from 12 to 3 increased the effect (pH 12: 84% ${\rightarrow}$pH 3: 95.6%). Pseudo first-order constants ($k_1$) of sonodegradation of naphthalene decreased as initial concentration of naphthalene increased (2.5 ppm: $27.3{\times}10^{-3}\;min^{-3}\;{\rightarrow}$ 10 ppm : $19.3{\times}10^{-3}\;min^{-3}$). Degradation efficiency of 2.5 ppm of naphthalene subjected to 28 kHz of ultrasonic irradiation was found to be 1.46 times as much as when exposed under 132 kHz (132 kHz: 56%, 28 kHz: 82.7%). Additionally, its $k_1$ constant was increased by 2.3 times (132 kHz: $2.4{\times}10^{-3}\;min^{-1}$, 28 kHz: $5.0{\times}10^{-3}\;min^{-1}$). $H_2O_2$ concentration measured 10 minutes after the exposure to 132 kHz of ultrasound, when compared with the measurement under frequency of 28 kHz, was 7.2 times as much. The concentration measured after 90 minutes, however, showed the difference of only 10%. (concentration of $H_2O_2$ under 28 kHz being 1.1 times greater than that under 132 kHz.) The $H_2O_2$ concentration resulting from 2.5 ppm naphthalene after 90 minutes of sonication at 24 kHz and 132 kHz were lower by 0.05 and 0.1 ppm, respectively, than the concentration measured from the irradiated M.Q. water (no naphthalene added.) Degradation efficiency of horn type (24 kHz) and bath type (28 kHz) ultrasound was found to be 87% and 82.7%, respectively, and $k_1$ was calculated into $22.8{\times}10^{-3}\;min^{-1}$ and $18.7{\times}10^{-3}\;min^{-1}$ respectively. Using the multi- frequency and mixed type of ultrasound system (28 kHz bath type + 24 kHz horn type) simultaneously resulted in combined efficiency of 88.1%, while $H_2O_2$ concentration increased 3.5 times (28 kHz + 24 kHz: 2.37 ppm, 24 kHz: 0.7 ppm.) Therefore, the multi-frequency and mixed type of ultrasound system procedure might be most effectively used for removing the substances that are easily oxidized by the OH radical.