• Title/Summary/Keyword: High-Dose

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Dependence Potential of the Synthetic Cannabinoids JWH-073, JWH-081, and JWH-210: In Vivo and In Vitro Approaches

  • Cha, Hye Jin;Lee, Kwang-Wook;Song, Min-Ji;Hyeon, Yang-Jin;Hwang, Ji-Young;Jang, Choon-Gon;Ahn, Joon-Ik;Jeon, Seol-Hee;Kim, Hyun-Uk;Kim, Young-Hoon;Seong, Won-Keun;Kang, Hoil;Yoo, Han Sang;Jeong, Ho-Sang
    • Biomolecules & Therapeutics
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    • v.22 no.4
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    • pp.363-369
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    • 2014
  • Synthetic cannabinoids (CBs) such as the JWH series have caused social problems concerning their abuse liability. Because the JWH series produces euphoric and hallucinogenic effects, they have been distributed illegally under street names such as "Spice" and "Smoke". Many countries including Korea have started to schedule some of the JWH series compounds as controlled substances, but there are a number of JWH series chemicals that remain uncontrolled by law. In this study, three synthetic CBs with different binding affinities to the $CB_1$ receptor (JWH-073, 081, and 210) and ${\Delta}^9$-tetrahydrocannabinol (${\Delta}^9$-THC) were evaluated for their potential for psychological dependence. The conditioned place preference test (unbiased method) and self-administration test (fixed ratio of 1) using rodents were conducted. $K_i$ values of the three synthetic cannabinoids were calculated as supplementary data using a receptor binding assay and overexpressed $CB_1$ protein membranes to compare dependence potential with $CB_1$ receptor binding affinity. All mice administered JWH-073, 081, or 210 showed significantly increased time spent at unpreferred space in a dose-dependence manner in the conditioned place preference test. In contrast, all tested substances except ${\Delta}^9$-THC showed aversion phenomenon at high doses in the conditioned place preference test. The order of affinity to the $CB_1$ receptor in the receptor binding assay was JWH-210 > JWH-081 >> JWH-073, which was in agreement with the results from the conditioned place preference test. However, no change in self-administration was observed. These findings suggest the possibility to predict dependence potential of synthetic CBs through a receptor binding assay at the screening level.

Characteristics of Kawasaki Disease Patients who are Unresponsive to High-dose Intravenous Immunoglobulin Therapy (가와사끼병에서 정맥용 면역글로불린 불응군의 특성)

  • Kook, Dong-Hyuk;Ko, Yong-Min;Lee, Keun-Young;Kim, Dong-Un;Lee, Kyung-Yil;Lee, Joon-Sung
    • Pediatric Infection and Vaccine
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    • v.15 no.2
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    • pp.180-187
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    • 2008
  • Purpose : We wanted to determine the characteristics of patients with Kawasaki disease (KD) who were unresponsive to intravenous immunoglobulin (IVIG). Methods : The patients with KD were divided into two groups: the IVIG responsive group (25 cases) and the IVIG unresponsive group (14 cases). We analyzed various parameters before and after the administration of IVIG, including the complete blood cell count with the differential count (%), the erythrocyte segmentation rate (ESR), the C-reactive protein (CRP) level and the protein and lipid profiles. Results : The IVIG unresponsive group had a prolonged duration of fever and a higher incidence of CAL compared to the IVIG responsive group (P<0.001, respectively). Before IVIG infusion, the neutrophil differential, the ESR and the CRP values were higher (P<0.001), and the total protein and albumin values were lower in the IVIG unresponsive group (P=0.01) compared to the IVIG responsive group. After IVIG infusion, there were no significant changes in the WBC count and CRP levels in the IVIG unresponsive group. The reduction of the HDL-cholesterol levels by IVIG was more significant in the unresponsive group (P=0.02). Conclusion : A more severe and prolonged inflammatory response occurred in the IVIG unresponsive group at an early stage, and this finding can be detected by such inflammatory parameters as the neutrophil count and the CRP and HDL-cholesterol levels after IVIG infusion.

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Effects of Herbal Complex on Blood Glucose in Streptozotocin-induced Diabetic Rats and in Mice Model of Metabolic Syndrome (생약복합제의 Streptozotocin 유발 당뇨 및 대사성증후군 모델 동물에서의 혈당에 미치는 효과)

  • Park, Han-Seok;Lee, Yeon-Sil;Choi, Se-Jin;Kim, Jin-Kyu;Lee, Yun-Lyul;Kim, Hyun-Gwen;Koo, Sam-Hoi;Ku, Dae-Hoy;Ki, Seung-Il;Lim, Soon-Sung
    • Korean Journal of Pharmacognosy
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    • v.40 no.3
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    • pp.196-204
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    • 2009
  • This study was carried out to investigate the in vivo and in vitro inhibitory effect of a traditional herbal complex (HC) extract prepared from a mixture of four oriental herbs (Dioscorea Rhizoma, Glycine soja Sieb. et Zucc, Bombycis corpus, Fermented Glycine soja) that have been widely used for the treatment and prevention of diabetes mellitus on hyperglycemia. The water extract of HC showed potent inhibitory effect on $\alpha$-glucosidase with $IC_{50}$ value of 1.24 mg/mL. Additionally, the ethanol extract of HC was also found to exhibit significant inhibitory effect against protein tyrosine phosphatase $1{\beta}$ ($PTP1{\beta}$), which is known as a major regulator of both insulin and leptin signaling. In the $PTP1{\beta}$ inhibitory assay, the most active n-hexane fraction obtained from the ethanol extract of HC, was identified as a mixture of fatty acid derivatives by gas chromatography-mass spectrometry (GC-MS). In high-fat diet-low dose streptozotocin (STZ)-induced diabetic rat, the water extract of HC improved the oral glucose intolerance as compared with rosiglitazone. HC also caused a marked decrease of body weight and fasting blood glucose and a significant improvement on glucose tolerance in metabolic syndrome mice model. These findings support that this traditional HC may be useful in the control of blood glucose in diabetes mellitus and metabolic syndrome.

Guidelines and Optimum Treatment for Agriculture Reuse of Reclaimed Water (농업적 용수재이용 수질기준을 고려한 적정 하수재처리에 관한 연구)

  • Jung, Kwang-Wook;Jeon, Ji-Hong;Ham, Jong-Hwa;Yoon, Chun-Gyeong
    • Korean Journal of Ecology and Environment
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    • v.36 no.3 s.104
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    • pp.356-368
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    • 2003
  • Water quality of effluent from wastewater treatment plants (WWTPS) was reviewed to examine the feasibility of agricultural reuse using USEPA and WHO guidelines. It might meet the guidelines for BOD and SS, however, the most critical microbiological concentration was too high and further treatment is required. The pilot study of three treatments were performed to reduce microbiological concentrations. The UV irradiation was proved to be very effective in disinfection of secondary level effluent, and about 30 mW ${\cdot}$ s/$cm^2$ of dose was suggested to meet the even most stringent USEPA guidelines. Slow sand filter demonstrated effective removal of bacteria, and effluent concentration of total coliform (TC), fecal coliform (FC), and E. coli. dropped from about 10,000/100 mL to 300, 200, and 150 MPN/100 mL, respectively, showing over 95% removal. These level of bacterial concentration sufficiently meet the WHO guidelines ($10^3\;{\sim}\;10^5$ FC/100 mL), and could meet the more stringent USEPA guidelines (200 FC/100 mL) if properly applied. Slow sand filter also provided about 50% removal of SS, turbidity, and BOD in addition to bacterial removal. The removal efficiency of pond system was relatively poor, but still showed over 85% removal and effluent concentration of TC, FC, and E. coli was all below 10,000/100 mL. The pond system alone could meet the WHO guidelines, but hardly meet the USEPA guidelines and further treatment might be necessary. Overall, three methods evaluated in the study treat the effluent to meet the WHO microbiological guidelines for agricultural reuse. The UV disinfection and slow sand filter might also could the USEPA guidelines, while the pond system can hardly meet the USEPA guidelines if applied alone. The WHO and USEPA guidelines were made based on data from upland field agricultural system and may not be directly applicable to the paddy field agricultural system. Therefore, national standards for agricultural reuse of reclaimed water should be made considering domestic agricultural systems as well as international guidelines. Also, further investigation is recommended to develop optimum and feasible treatment measures for agricultural reuse of effluent from WWTPs.

Expression of CsRCI2s by NaCl stress reduces water and sodium ion permeation through CsPIP2;1 in Camelina sativa L.

  • Kim, Hyun-Sung;Lim, Hyun-Gyu;Ahn, Sung-Ju
    • Proceedings of the Korean Society of Crop Science Conference
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    • 2017.06a
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    • pp.194-194
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    • 2017
  • Camelina (Camelina sativa L.) is a potential bio-energy crop that has short life cycle about 90 days and contains high amount of unsaturated fatty acid which is adequate to bio-diesel production. Enhancing environmental stress tolerance is a main issue to increase not only crop productivity but also big mass production. CsRCI2s (Rare Cold Inducible 2) are cold and salt stress related protein that localized at plasma membrane (PM) and assume to be membrane potential regulation factor. These proteins can be divide into C-terminal tail (CsRCI2D/E/F/G) or no-tail group (CsRCI2A/B/C/H). However, function of CsRCI2s are less understood. In this study, physiological responses and functional characterization of CsRCI2s of Camelina under salt stress were analyzed. Full-length CsRCI2s (A/B/E/F) and CsPIP2;1 sequences were confirmed from Camelina genome browser. Physiological investigations were carried out using one- or four-week-old Camelina under NaCl stress with dose and time dependent manner. Transcriptional changes of CsRCI2A/B/E/F and CsPIP2;1 were determined using qRT-PCR in one-week-old Camelina seedlings treated with NaCl. Translational changes of CsRCI2E and CsPIP2;1 were confirmed with western-blot using the antibodies. Water transport activity and membrane potential measurement were observed by cRNA injected Xenopus laevis oocyte. As results, root growth rate and physiological parameters such as stomatal conductance, chlorophyll fluorescence, and electrolyte leakage showed significant inhibition in 100 and 150 mM NaCl. Transcriptional level of CsPIP2;1 did not changed but CsRCI2s were significantly increased by NaCl concentration, however, no-tail type CsRCI2A and CsRCI2B increased earlier than tail type CsRCI2E and CsRCI2F. Translational changes of CsPIP2;1 was constitutively maintained under NaCl stress. But, accumulation of CsRCI2E significantly increased by NaCl stress. CsPIP2;1 and CsRCI2A/B/E/F co-expressed Xenopus laevis oocyte showed decreased water transport activity as 61.84, 60.30, 62.91 and 76.51 % at CsRCI2A, CsRCI2B, CsRCI2E and CsRCI2F co-expression when compare with single expression of CsPIP2;1, respectively. Moreover, oocyte membrane potential was significantly hyperpolarized by co-expression of CsRCI2s. However, higher hyperpolarized level was observed in tail-type CsRCI2E and CsRCI2F than others, especially, CsRCI2E showed highest level. It means transport of $Na^+$ ion into cell is negatively regulated by expression of CsRCI2s, and, function of C-terminal tail is might be related with $Na^+$ ion influx. In conclusion, accumulation of NaCl-induced CsRCI2 proteins are related with $Na^+$ ion exclusion and prevent water loss by CsPIP2;1 under NaCl stress.

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The Fabricating and Utilizing of the Transmission Scan Tool for I-131 Whole Body Scan (I-131 전신 스캔을 위한 Transmission Scan Tool 제작과 활용)

  • Shin, Chae-Ho;Pyo, Sung-Jai;Kim, Bong-Su;Cho, Yong-Gyi;Jo, Jin-Woo;Kim, Chang-Ho
    • The Korean Journal of Nuclear Medicine Technology
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    • v.13 no.1
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    • pp.40-46
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    • 2009
  • Purpose: A whole body scan using a radioactive iodine (I-131) for the patients with differentiated thyroid cancer is generally an useful method to detect the remnant thyroid tissue, recurred lesion or metastasis lesion after a surgery. The high dose treatment using the radioactive iodine recently tends to increase, and a hospitalization wait for the treatment has been delayed for several months. In this hospital, the treatable patients per week were increased in number through expanding a water-purifier tank and the examination time also increased as the I-131 whole body scan patients increased. Improvement for this problem, this research reduce the existing examination time and classifying the lesion's exact position intended to by fabricating and utilizing the transmission scan tool and an excellent resolution for whole body imaging. Materials and Methods: After conducting the whole body scan for patients who visited the department from February to July 2008 and received the I-131 whole body scan using the ORBITER Gamma Camera. A rail was installed in the examination table for the transmission scan for show a contour of surface area and then the transmission image was obtained and fused to the whole body scan through fabricating the tool to put a flood phantom of diluted 2 mCi $^{99m}Tc$-pertechnetate. Results: Fused image of I-131 whole body scan and the transmission scan had the excellent resolution to discriminate an oral cavity or salivary gland region, neck region's lesion, and metastasis region's position through a simple marking, and could reduce the examination time of 8~28 minutes because without the additional local image. Conclusions: In I-131 whole body scan, the transmission scan can accurately show a contour of surface area through the attenuation of radioactivity, and is useful to indicate the remnant thyroid tissue or metastasis lesion's position by improving the resolution through the fusion image with alreadyexecuted I-131 whole body scan. Also, because the additional local image is not necessary, it can reduce the time required for the examination. It will extensively apply to other clinical examinations to be helpful for identifying an anatomical position because it shows the contour of surface area.

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Performance Evaluation of Breast Specific Gamma Imaging (Breast Specific Gamma Imaging 장비의 성능평가)

  • Cha, Eun-Sun;Kwak, In-Suk;Noh, Ik-Sang;Yeon, Joon-Ho;Kim, Ki;Choi, Choon-Ki;Seok, Jae-Dong
    • The Korean Journal of Nuclear Medicine Technology
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    • v.14 no.1
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    • pp.24-27
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    • 2010
  • Purpose: Early diagnosis of breast is of the utmost importance to improve prognosis. We have a limitation for mammography and sonography detecting small cancer. Clinical importance of Breast Specific Gamma Imaging (BSGI) has improved for that reason. So We studied performance evaluation test of count rate and resolution with high sensitivity to the low dose of BSGI. Materials and Methods: BSGI of Dilon 6800, point source of $^{99m}Tc$ from 1.85~148 MBq (0.05~4 mCi) at the intervals of 1.85~37 MBq (0.05~1 mCi) was used for the test. Performance evaluation method was performed for measuring deadtime for choosing at the 5 different point in the useful field of view (UFOV), acquired image for 60 seconds. Compared with reference of clinical uptake distribution of breast, activity increased according to the distance change 10, 20, 30, 40, 50 mm in the useful field of view. Results: Counting curve increased according to the activity from 1.85 MBq (0.05 mCi) to the 74 MBq (2 mCi), and it change flat shape over 74 MBq (2 mCi). The variation of the full width of half maximum (FWHM) to the distance is 4.05, 4.73, 5.77, 6.90, 8.00, 9.32 mm in 1.85 MBq (0.05 mCi), 4.30, 4.80, 5.90, 7.00, 8.10, 9.07 mm in 3.7 MBq (0.1 mCi), 4.90, 5.60, 6.20, 7.20, 8.20, 9.10 mm in 5.55 MBq (0.15 mCi), 5.30, 6.10, 6.60, 7.00, 7.90, 8.70 mm in 7.40 MBq (0.2 mCi). Conclusion: Distortions of image would be acquired because of the deadtime in BSGI. We found out the fact that specification of $^{99m}Tc$ reaction under 74 MBq (2 mCi) for BSGI. Second, FWHM distribution change from varied distance from the detector, clearly distinguished the location of the lesion.

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Study of Failure Mode and Effect Analysis in Brachytherapy (근접방사선치료에 관한 사고유형과 영향분석 연구)

  • Lee, Soon Sung;Park, Dong Wook;Shin, Dong Oh;Kim, Dong Wook;Kim, Kum Bae;Oh, Yoon-Jin;Kim, Juhye;Kwon, Na Hye;Kim, Kyeong Min;Choi, Sang Hyoun
    • Journal of the Korean Society of Radiology
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    • v.11 no.7
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    • pp.627-635
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    • 2017
  • Brachytherapy is generally performed in conjunction with external radiation therapy, and the treatment course is very complicated, which can lead to radiation accidents. In order to solve this problem, we designed the process map by applying the failure mode and effects analysis (FMEA) method to the Brachytherapy and scored the risk priority number (RPN) for each treatment course based on this process map. The process map consisted of five steps, Patient consulting", "Brachytherapy simulation", "CT simulation", "Brachytherapy treatment planning" and "Treatment". In order to calculate the RPN, doctor, medical physicist, dose planners, therapist, and nurse participated in the study and evaluated occurrence, severity, and lack of detectability at each detail step. Overall, the process map is preceded by a patient identification procedure at each treatment stage, which can be mistaken for another patient, and a different treatment plan may be established to cause a radiation accident. As a result of evaluating the RPN for the detailed steps based on the process map, overall "Patient consulting" and "Brachytherapy treatment planning" step were evaluated as high risk. The nurses showed a tendency to be different from each other, and the nurses had a risk of 55 points or more for all the procedures except "Treatment", and the "Brachytherapy simulation" step was the highest with 88.8 points. Since the treatment stage differs somewhat for each medical institution performing radiotherapy, it is thought that the risk management should be performed intensively by preparing the process map for each institution and calculating the risk RPN.

Results of Stereotactic Radiosurgerv with Linear Accelerator for Intracranial Arteriovenous Malformation (두개강내 동정맥기형에서 선형가속기를 이용한 방사선수술의 결과)

  • Lee Kang Kyoo;Park Kyung Ran;Lee Jong Young;Lee Yong Ha
    • Radiation Oncology Journal
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    • v.15 no.3
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    • pp.215-224
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    • 1997
  • Purpose : Stereotactic radiosurgery with external beam irradiation successfully obliterates carefully selected intracranial arteriovenous malformation (AVM) . We Present clinical and radiological long term results after treatment with a single high dose irradiation using a linear accelerator. Materials and Methods : Rrom January 1991 to June 1994, fifteen patients with intracranial AVM were treated in our hospital with the stereotactic radiosurgery using a linear accelerator. The radiation was delivered using a 6 MV linear accelerator. The prescribed doses at the isocenter varied from 1800 to 2500cGy (median : 2000cGy) and were given as a sin91e fraction. The radiation doses at the periphery of the lesion typically corresponded to the 80-90% isodose line. In 14 patients, complete clinical and/or radiological follow-up examination were available. Results : Angiography was available in 13 patients with a follow-up Period from 18 months to 27 months. Of 13 patients, the overall complete obliteration rate was 92.3% (12 patients). This incidence did not correlate with lesion size. Seizure, headache and progressive neurologic deficit were complete recovered. One Patient experienced hemorrhage at 2 months after treatment. One patient developed radiation induced brain edema in the white matter surrounding nidus at 16 months after treatment and showed complete resolution of the edema in MR image obtained at 27 months after treatment. After a follow-up period of up to 6 years, no radiation induced severe late complications occurred. Conclusion : We conclude that stereotactic radiosurgery using a linear accelerator is an effective and safe therapy for symptomatic and surgically inaccessible intracranial AVMs and the results compare favorably to the more expensive and elaborate systems that are currently available for stereotactic radiosurgery.

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Hypoglycemic and Hypolipidemic Effects of Orostachys japonicus with Medicinal Herbs in Streptozotocin-Induced Diabetic Rats (생약재와 와송 추출물의 복합조성물이 Streptozotocin 유발 당뇨성 흰쥐의 혈당강하 및 혈중 지질성분에 미치는 영향)

  • Lee, Soo-Jung;Shin, Jung-Hye;Ju, Jong-Chan;Kang, Shin-Kwon;Sung, Nak-Ju
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.42 no.4
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    • pp.587-594
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    • 2013
  • The hypoglycemic and hypolipidemic effects from Wa-song (Orostachys japonicus) extracts with mixtures of medicinal herbs (such as Baekbokyung, Changchul and Sa-in) were evaluated in the streptozotocin (STZ)-induced diabetic rats. Thirty-five Sprague-Dawley rats were assigned to five groups; normal, diabetic control (D-control), a group fed a medicinal herbs mixture (D-MH), and a group fed composites of O. japonicus with mixtures of medicinal herbs (1:1, D-MHOA and 3:1, D-MHOB). All were fed on their diet for 4 weeks. After 4 weeks, the body weight of all experimental groups increased compared to the diabetic control group, with the D-MHOB group having a significantly higher increase. Fasting glucose levels in all experimental groups (compared to the D-control group) significantly decreased after 2 weeks, but between 2~3 weeks, the levels in the D-MH group were similar to the D-MHOA group. After 4 weeks, the fasting glucose level of the D-MHOB group was the lowest compared to the other groups. In a test of oral glucose tolerance, blood glucose levels were highest 60 minutes after feeding glucose; however this level improved significantly in the groups fed an experimental diet compared to the D-control group. Glycosylated hemoglobin levels were 1.9 times higher in the D-control group than the normal (3.9%), but levels in the experimental groups were significantly decreased in D-MHOA and D-MHOB groups compared to the D-MH group. In the high amounts of O. japonicus to medicinal herbs mixture, total lipids and cholesterol significantly decreased in the serum, while HDL-C levels increased. GPT activity was significantly lower in the D-MHOB group compared to the other groups. Lipid peroxide levels decreased in the D-MHOA and D-MHOB groups compared to the D-MH group. Antioxidant activity was higher depending on the dose of O. japonicus. Overall, O. japonicus exhibited effective hypoglycemic and hypolipidemic actions enhanced by a combination of medicinal herbs.