• Nutrition Research and Practice
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• v.14 no.5
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• pp.425-437
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• 2020

BACKGROUND/OBJECTIVES: Different fatty acids exert different health benefits. This study investigated the potential protective effects of perilla, olive, and safflower oils on high-fat diet-induced obesity and colon inflammation. MATERIALS/METHODS: Five-week old, C57BL/6J mice were assigned to 5 groups: low-fat diet (LFD), high-fat diet (HFD) and high-fat diet supplemented with-perilla oil (HPO), olive oil (HOO), and safflower oil (HSO). After 16 weeks of the experimental period, the mice were sacrificed, and blood and tissues were collected. The serum was analyzed for obesity- and inflammation-related biomarkers. Gene expression of the biomarkers in the liver, adipose tissue, and colon tissue was analyzed. Micro-computed tomography (CT) analysis was performed one week before sacrifice. RESULTS: Treatment with all the three oils significantly improved obesity-induced increases in body weight, liver weight, and epididymal fat weight as well as serum triglyceride and leptin levels. Treatment with perilla oil (PO) and safflower oil (SO) increased adiponectin levels. The micro-CT analysis revealed that PO and SO reduced abdominal fat volume considerably. The mRNA expression of lipogenic genes was reduced in all the three oilsupplemented groups and PO upregulated lipid oxidation in the liver. Supplementation of oils improved macroscopic score, increased colon length, and decreased serum endotoxin and proinflammatory cytokine levels in the colon. The abundance of Bifidobacteria was increased and that of Enterobacteriaceae was reduced in the PO-supplemented group. All three oils reduced proinflammatory cytokine levels, as indicated by the mRNA expression. In addition, PO increased the expression of tight junction proteins. CONCLUSIONS: Taken together, our data indicate that the three oils exert similar anti-obesity effects. Interestingly, compared with olive oil and SO, PO provides better protection against high-fat diet-induced colon inflammation, suggesting that PO consumption helps manage inflammation-related diseases and provides omega-3 fatty acids needed by the body.

• The Journal of Internal Korean Medicine
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• v.29 no.1
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• pp.177-188
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• 2008

Objectives : This study was performed to investigate the anti-fibrogenic effect of Artemisiae Capillaris Herba on cultured rat hepatic stellate cells. Materials and Methods : Hepatic stellate cells(HSC-T6) were treated with various concentrations of Artemisiae Capillaris Herba extract for 24 hours. The extraction was done either with distilled water or 50% EtOH. After the treatment, cell viability, proliferation, procollagen levels and the mRNA of the collagen type 1a2 and ASMA were measured by using MTT assay, BrdU assay, RT-PCR, and Procollagen Type I C-peptide EIA Kit. Results : The viability and proliferation of the hepatic stellate cells were decreased as the concentration increased. The mRNA expression decreased consistently with the volume of the secreted procollagen with the extraction made with distilled water, which indicates the herb has inhibitory effect on fibrogenesis of the liver by regulating one of the fibrosis associated genes in transcription. However, it increased in 50% EtOH extraction, which shows that a more stable reaction is expected of the extraction made with distilled water than the extraction made with 50% EtOH. The production of procollagen was decreased by a low-concentration treatment with Artemisiae Capillaris Herba, but increased by a high concentration. It seemed that the cells were responding to Artemisiae Capillaris Herba in low- concentrations, thus producing small amounts of collagen. When the drug was administered at high enough concentration to give direct toxicity to cells, the ability of cells to produce collagen was activated, and the overproduction of collagen was observed as an undesirable results. Conclusion : These results suggest that Artemisiae Capillaris Herba is beneficial in the treatment of cirrhotic patients as well as for the patients with chronic hepatitis when extracted with water in the proper concentrations.

• The Journal of Korean Medicine
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• v.31 no.3
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• pp.1-7
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• 2010

Objectives: To introduce to TKM scientific dose conversion methods of human to animal or animal to human for new drug investigations. Methods: We searched guidelines of the FDA and KFDA, and compared them with references for drug-dose conversion from various databases such as PubMed and Google. Then, we analyzed the potential issues and problems related to dose conversion in safety documentation of new herbal drugs based on our experiences during Investigational New Drug (IND) applications of TKM. Results: Dose conversion from human to animal or animal to human must be appropriately translated during new drug development. From time to time, investigators have some difficulty in determining the appropriate dose, because of misunderstandings of dose conversion, especially when they estimate starting dose in clinical or animal studies to investigate efficacy, toxicology and mechanisms. Therefore, education of appropriate dose calculation is crucial for investigators. The animal dose should not be extrapolated to humans by a simple conversion method based only on body weight, because many studies suggest the normalization method is based mainly on body surface area (BSA). In general, the body surface area seems to have good correlation among species with several parameters including oxygen utilization, caloric expenditure, basal metabolism, blood volume and circulating plasma protein. Likewise, a safety factor should be taken into consideration when deciding high dose in animal toxicology study. Conclusion: Herein, we explain the significance of dose conversion based on body surface area and starting dose estimation for clinical trials with safety factor.

• The Korean Journal of Nuclear Medicine
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• v.5 no.2
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• pp.41-56
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• 1971

The pathogenetic mechanisms of anemia in patients with chronic liver disease were observed. Seventeen patients with moderate to advanced hepatic diseass were studied by various methods. Only patients without previous blood loss were included: 14 had cirrhosis, 2 had active chronic hepatitis, and one had inferior vena cava obstruction with associated liver cirrhosis. The followings were the results: 1. The anemia based on red blood cell count, Hb., and Ht. was found in 76.5-78.6% of the patients. 2. Red cell indices indicated that normo-macrocytic and normochromic anemia was present is the majority of the patients. 3. No evidence of megaloblastic anemia was found on the basis of the morphological examinations. 4. Serum iron, TIBC, % saturation and iron content in the bone marrow indicated that iron deficiency anemia was present in about half of the patients. 5. In the view of the erythrocyte dynamics, primary increase in the red cell destruction was ascribed to the cause of the anemia. 6. Decrease in the red cell survival time was not correlated with MCV, % saturation and S.L. ratio. Also, hemoglobin level was not correlated with MCV, % saturation and $T_{50}Cr$. Therefore, multiple causes may be involved in the pathogenesis of the anemia. 7. Anemia as determined by the red cell volume was found in only 60% of the patients. It may be possible that hemodilutional anemia is present.

• Toxicological Research
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• v.35 no.2
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• pp.181-190
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• 2019

Lentinus squarrosulus (Mont.) is an edible wild mushroom with tough fruiting body that belongs to the family Polyporaceae. It is used in ethnomedicine for the treatment of ulcer, anaemia, cough and fever. Recent studies have demonstrated its anticancer, anti-diabetic and antioxidant properties. However, little or no information is available regarding the bioactive components and toxicological study of wild dried L. squarrosulus. Therefore, this study investigated the bioactive components of aqueous extract of boiled wild dried L. squarrosulus and its toxicological effects in rats. The extract of L. squarrosulus was subjected to GC-MS analysis. The acute toxicity test was performed by oral administration of a single dose of up to 5,000 mg/kg extract of L. squarrosulus. In subacute study, the rats were orally administered extract of L. squarrosulus at the doses of 500, 1,000 and 1,500 mg/kg body weight daily for 14 days. The haematological, lipid profile, liver and kidney function parameters were determined and the histopathology of the liver and kidney were examined. The GC-MS analysis revealed the presence of bioactive compounds; 1-tetradecene, fumaric acid, monochloride, 6-ethyloct-3-yl ester, 9-eicosene, phytol, octahydropyrrolo[1,2-a]pyrazine and 3-trifluoroacetoxypentadecane. In acute toxicity study, neither death nor toxicity sign was recorded. In the sub-acute toxicity study, significant differences (p < 0.05) were observed on creatinine, aspartate aminotransferase, alanine aminotransferase, total cholesterol, triglycerides and high-density lipoprotein cholesterol. Whilst no significant differences (p > 0.05) were observed on packed cell volume, heamoglobin, red blood cell, white blood cell and alkaline phosphatase, in all the tested doses. No histopathological alterations were recorded. Our findings revealed that aqueous extract of L. squarrosulus may have antimicrobial, antinocieptive and antioxidant properties based on the result of GC-MS analysis. Results of the toxicity test showed no deleterious effect at the tested doses, suggesting that L. squarrosulus is safe for consumption at the tested doses.

• Journal of radiological science and technology
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• v.38 no.2
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• pp.107-114
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• 2015

The purpose is reducing radiation dose while maintaining of image quality in liver dynamic CT(LDCT) scan, by protocols generally used and the tube voltage set at a low level protocol compared to the radiation dose and image quality. The target is body mass index, 18.5~24 patients out of 40 patients who underwent the ACT(abdominal CT). Group A(tube voltage : 120kVp, SAFIRE strength 1) of 20 people among 40 people, to apply the general abdominal CT scan protocol, group B(tube voltage : 100kVp, apply SAFIRE strength 0~5) was 20 people, set a lower tube voltage. Image quality evaluation was setting a region of interest(ROI) in the liver parenchyma, aorta, superior mesenteric artery (SMA), celiac trunk, visceral fat of arterial phase. In the ROI were compared by measuring the noise, signal to noise ratio(SNR), contrast to noise ratio(CNR), CT number. In addition, qualitative assessments to evaluate two people in the rich professional experience in Radiology by 0-3 points. We compared the total radiation dose, dose length product(DLP) and effective dose, volume computed tomography dose index(CTDIvol). The higher SAFIRE in the tube voltage 100 kVp, noise is reduced, CT number was increased. Thus, SNR and CNR was increased higher the SAFIRE step. Compared with the tube voltage 120kVp, noise, SNR, CNR was most similar in SAFIRE strength 2 and 3. Qualitative assessment SAFIRE strength 2 is the most common SAFIRE strength 2 the most common qualitative assessment, if the tube voltage of 100kVp when the quality of the images better evaluated was SAFIRE strength 1. Dose was reduced from 21.69%, in 100kVp than 120kVp. In the case of a relatively high BMI is not LDCT scan, When it is shipped from the factory tube voltage is set higher, unnecessary radiation exposure when considering the reality that is concerned, when according to the results of this study, set a lower tube voltage and adjust the SAFIRE strength to 1 or 2, the radiation without compromising image quality amount also is thought to be able to be reduced.

• Journal of Korean Medicine Rehabilitation
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• v.24 no.2
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• pp.65-81
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• 2014

Objectives This study was carried out to find out the anti-osteoarthritic effects of Mahwangbujaseshin- tang (Mahuangfuzixixintang ) on the monosodium iodoacetate (MIA)-induced osteoarthritis rats. Methods Osteoarthritis was induced by injecting MIA ($50{\mu}l$) into the knee joint of rats. Rats were divided into a 3 groups (n=7). The injection did not fit the normal group. A week later, after the injection of MIA, while control group took normal saline 2 ml, the extract of Mahwangbujaseshin-tang (Mahuangfuzixixintang ) (MBST) (200 mg/kg) was injected to treated group. After that, we examined hind paw weight bearing ability, functions of liver and kidney, serum TNF-$\alpha$, IL-$1{\beta}$, IL-6, $PGE_2$, $LTB_4$, TIMP-1, MMP-9 and hematology. Volume of cartilage was measured by micro CT arthrography. Injury of synovial tissue was measured by H & E, Safranin-O immunofluorescence. Results 1) DPPH and ABTS free radical scavenging activity of MBST was increased according to concentration of MBST and total phenolic contents were in high level. 2) In RAW 264.7 cells, ROS production was significantly decreased in MBST (at 10, $100{\mu}g/ml$) and NO was also decreased but meaningless in MBST (at $100{\mu}g/ml$). 3) In RAW 264.7 cells, IL-6 production was significantly decreased in MBST (at $100{\mu}g/ml$) and TNF-$\alpha$ and IL-$1{\beta}$ production were also decreased but meaningless in MBST (at $100{\mu}g/ml$). 4) In hind legs weight-bearing measurement, level of weight-bearing was increased. 5) Functions of liver and kidney were not affected. 6) TNF-$\alpha$, IL-$1{\beta}$, IL-6, $PGE_2$, $LTB_4$, MMP-9 and TIMP-1 production were significantly decreased. 7) In hematology, the levels of neutrophils, monocytes were significantly decreased and the levels of white blood cells, lymphocytes were also decreased but meaningless. 8) In micro CT-arthrography, cartilage volume was significantly increased. 9) Histopathologically, injury on cartilage and synovial membrane of MBST group was decreased. Conclusions Based on all results mentioned above, Mahwangbujaseshin-tang (Mahuangfuzixixintang) is believed to be meaningful for suppressing the progress of osteoarthritis. And it is related to inhibiting the activity of inflammatory cytokine and injury of volume in cartilage.

• Korean Journal of Exercise Nutrition
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• v.13 no.1
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• pp.1-7
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• 2009

It has been shown that both caloric restriction and exercise, enhances glucose uptake through translocation of GLUT-4 protein. It remains unclear how exercise and caloric restriction affect the changes in VAMP (vesicle-associated membrane protein) in skeletal muscle and GLUT-2 in liver. This study investigated the effects of exercise training and caloric restriction on the expressions of glucose transport relating proteins in muscle and liver tissues in diabetic rats. Forty male Sprague-Dawley rats (250±10 g; 8 week in age) were assigned equally to four different groups; control (C), exercise only (E), dietary restriction only (D) and dietary restriction and exercise (DE). Daily food consumption was monitored to establish baseline intake. Both C and E groups consumed baseline food intake while D and DE groups were provided with only 60% of baseline total food intake. Forty-eight hours after intraperitoneal injection of STZ (50 mg/kg), diabetes was confirmed (8-hr fasting blood glucose levels ≥300 mg/dl). Rats in the E and DE groups exercised on a motorized treadmill for 30 min/d, 5 days/week for 4 weeks (5 min running at 3 m/min, 0% grade; 8 m/min for the next 5min, and then 15 m/min for 20 min). Rats were sacrificed 48 hrs after the last bout of exercise. Soleus muscle and liver were extracted to analyze for GLUT-4, VAMP-2, and GLUT-2, respectively. All variables were analyzed using the Western Blotting technique. All values were expressed as optical volume measured by optical density. A Two-way ANOVA was used to examine the difference between groups and applied Duncan's test for post-hoc. No significant differences in GLUT-2 expression were found among groups. However, E (280133±13228 arbitrary units{AU}) and DE (268833±14424 AU) groups showed significantly higher (p<.001) levels of GLUT-4 as compared with C (34461±2099 AU) and D groups (27847±703 AU). VAMP-2 protein expression increased (p<.001) in E (184137±7803 AU) and DE (189800±10856 AU) groups as compared to C (74201±8296AU) and D (72967±863 AU) groups. These results suggest that either exercise with or without caloric restriction increases the up-regulation of GLUT-4 and VAMP-2 in skeletal muscle of diabetic rats. However, GLUT-2 protein in liver was not affected by either exercise or exercise with caloric restriction.

• Journal of the Korean Society of Radiology
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• v.82 no.4
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• pp.876-888
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• 2021

Purpose The aim of this study was to compare the diameter and volume of liver metastases on CT images in relation to overall survival and tumor response in patients with gastric cancer liver metastases (GCLM) treated with chemotherapy. Materials and Methods We recruited 43 patients with GCLM who underwent chemotherapy as a first-line treatment. We performed a three-dimensional quantification of the metastases for each patient. An independent survival analysis using the Response Evaluation Criteria in Solid Tumors (RECIST) was performed and compared to volumetric measurements. Overall survival was evaluated using Kaplan-Meier analysis and compared using Cox proportional hazard ratios following univariate analyses. Results When patients were classified as responders or non-responders based on volumetric criteria, the median overall survival was 23.6 months [95% confidence interval (CI), 8.63-38.57] and 7.6 months (95% CI, 3.78-11.42), respectively (p = 0.039). The volumetric analysis and RECIST of the non-progressing and progressing groups showed similar results based on the Kaplan-Meier method (p = 0.006) and the Cox proportional hazard model (p = 0.008). Conclusion Volumetric assessment of liver metastases could be an alternative predictor of overall survival for patients with GCLM treated with chemotherapy.

• Archives of Pharmacal Research
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• v.20 no.4
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• pp.318-323
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• 1997

The experimental hepatic cirrhosis was induced either by bile duct ligation (BDL) or by pretreatment with dimethyinitrosamine (DMNA). The pharmacokinetics of theophylline were studied after a single intravenous or a single oral administration. Using the ultrafiltration method, protein-drug binding experiments were also carried out. The bilirubin level was several-fold increased by BDL, but not by DMNA treatment. The albumin content was decreased in both cirrhotic groups. The total clearance (Clt, ml/kg/hr) of theophylline in both hepatic cirrhosis groups significantly decreased and the terminal half-life $(t_{1/2})$ in the cirrhotic rats was increased about two-fold after intravenous and oral administration. The volume of distribution at steady state (Vdss, ml/kg) was increased slightly in the cirrhotic groups. Protein binding in BDL $(8.67{\pm}4.85%)$ decreased about four-folds, but in DMNA $(73.00{\pm}9.85%)$ similar result war observed as compared with the control. Increased free fraction of theophylline did not increase the volume of distribution in BDL. Therefore decreased total body clearance of theophylline was mainly due to decreased intrinsic clearance of theophylline in the liver. The absolute bioavailability of theophylline in these experiments was between 63.8 and 72.8%(66.1% in BDL, 63.8% in Sham operated and Control, 72.8% in DMNA). These results suggest that in the experimental hepatic cirrhosis model, administration route does not affect the disposition of theophylline.