This study was performed to investigate the toxic effect of pyrrolizidine alkaloids from symphytum officinale i n rat. For this experiment, 120 male and female rats of Sprague-Dawley strain were used. The experimental groups were divided into five: Group CM and CF served as normal control with its gender. Group EM1 and EF1 were fed a 1% Symphytum officinal extract diet for 8 weeks. Group EM2 and EF2 fed a diet containing 2% extract diet. 4% extract diet into group EM3 and EF3 and 8% extract diet into group EM4 and EF4 were given. The results were as follows: 1. The major alkaloids of Symphytum officinale extract were symphytine, echmidine, and lasiocarpine. The amounts of total alkaloid were 168 $\mu\textrm{g}$ PAs/$m\ell$ extract. And contents of Pas in leaves were 0.05% wt.. 2. Total serum bilirubin concentrations increased significantly in group EM2, EM3, and EM4. Group EF1, EF2, EF3, and EF4 showed statistical significance for the group CF (p<0.05). 3. Aspartate transaminase activities were increased significantly in group EM3 and EM4 (p<0.05). Aspartate transaminase activities of EF1, EF2, EF3, and EF4 showed statistical significance for the group CF (p<0.05). 4. Alanine transaminase activities increased significantly in group EM3, EM4 (p<0.05). Alanine transaminase activities of EF1, EF2, EF3, and EF4 showed statistical significance for the group CF (p<0.05). 5. Alkaline phosphatase activities increased significantly in group EM2, EM3, and EM4 (p<0.05). Alkaline phosphatase activities of EF1, FE@, EF3, and EF4 showed statistical sigmificance for the group CF (p<0.05). 6. istopathological analysis of liver specimens from group EM3 and EM4 showed focal necrosis, periportal necrosis and apoptpsis. Hepatocytes obtained from group EM2 showed fatty change and hydropic degeneration in group EM3 and EM4. Chromatolysis and chromatin margination was shown in group EF2 and EF3. With the above results, it was demonstrated that the Symphytum officinal extract could induce functional change of liver, and histopathological change of liver in rats fed a diet containing extract. In conclusion, because of the risk of intoxication or adverse effect, the composition, dosage and mode of administration of herbal products should be monitored strictly. And this study serves as a reminder that herbal as well as orthodox medications may have serious side effects.
Functional characteristics of citrus products fermented with lactic acid bacterium and yeast were investigated. Flavonoid composition of fermented citrus extracts increased significantly compared to control, leading to increases of naringenin and hesperetin concentrations. All citrus extracts showed anti-apoptotic effects in HepG2 cells regardless of fermentation, with citrus-fermented products showing greater anti-apoptotic effect and intracellular Reactive Oxygen Species content reduction compared to native citrus extracts. Male Sprague-Dawley rats were orally dosed with native or fermented citrus extracts. Singnificantly higher body weight reductions were observed in higher fermented citrus-dosed (100 mg/kg body weight) group compared to the other groups. Plasma total cholesterol level was slightly, but not significantly, reduced. Fatty liver formation induced by high-fat diet was significantly suppressed in rats administered with fermented citrus extracts. Results suggest fermented citrus extracts have potent anti-apoptotic and anti-oxidative activities in vitro, and inhibitory activity against fatty liver formation by high-fat diet in vivo.
Objectives : The aim of this study was to experiment the antitumor activity of Agrimonia pilosa Ledebour (APL) in human stomach cancer (AGS) cell lines (in vitro) and male C57BL/6J mouse (in vivo). Methods : The effects of the ethanol extract from the plant on several transplantable rodent tumors were investigated in vitro by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxy phenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) assay. DNA content analysis and Western blot analysis. Agrimonia pilosa Ledebour (APL) was given to rats with Lewis Lung Carcinoma (LLC) cells. The experimental rats were divided into 3 groups in vivo. Saline was injected into the abdominal cavity in the first group, 50 mg/kg APL was injected into the abdominal cavity in the second group and 100 mg/kg was injected into the abdominal cavity in the third group. After that, we checked their tumor volume periodically. Results : At first, human gastric cancer (AGS) cell lines (in vitro) showed decreased cell viability, and increased $sub-G_1$ contents. When we experimented rat intestinal epithelial (RIE)l as same condition, this result didn't show. With this, compared to normal cells, Agrimonia pilosa Ledebour (APL) led selectively to the extinction of cells only in human gastric cancer. Moreover, we showed that the traditional herbal medicine APL induced caspase-dependent apoptosis in AGS cells. Next, APL inhibited the growth of LLC-bearing mouse tumor. However, we could not verify APL induced caspase-dependent apoptosis in LLC-bearing mouse tumor. Conclusions : The roots of Agrimonia pilosa Ledebour (APL) contain some antitumor constituents.
Lee Han Chang;Yeam Mi Jung;Kim Gun Ho;Choi Kang Duk;Lee Seoung Hee;Shim Insop;Lee Hye Jung;Hahm Dae Hyun
Journal of Physiology & Pathology in Korean Medicine
/
v.17
no.6
/
pp.1393-1403
/
2003
The genetic effects of restraint stress challenge on HPA axis and the therapeutic effect of Boshimgeonbi-Tang on the stress were studied with cDNA microarray analyses on hypothalamus using an immobilization-stress mouse as stress model. Male CD-1 mice were restrained in a tightly fitted and ventilated vinyl holder for 2hours once a day, and this challenge was repeated for seven consecutive days. The body weights of the immobilization-stress mice were diminished about 25 percent degree as compared to normal ones. Seven days later, total RNA was extracted from the organs of the mouse, body-labeled with CyDye/sup TM/ fluorescence dyes (Amersham Bioscience Co., NJ), and then hybridized to cDNA microarray chip. Scanning and analyzing the array slides were carried out using GenePix 4000 series scanner and GenePix Pro/sup TM/ analyzing program, respectively. The expression profiles of 109 genes out of 6000 genes on the chip were significantly modulated in hypothalamus by the immobilization stress. Energy metabolism-, lipid metabolism-, apoptosis- and signal transduction-related genes were transcriptionally activated whereas DNA repair-, protein biosynthesis-, and structure integrity-related genes were down-regulated in hypothalamus. The 58 genes were up-regulated by the mRNA expression folds of 1.5 to 7.9. and the 51 genes were down-regulated by 1.5 - 3.5 fold. The 20 genes among them were selected to confirm the expression profiles by RT-PCR. The mRNA expression levels of Tnfrsf1a (apoptosis), Calm2 (cell cycle), Bag3 (apoptosis), Hspe1 (protein folding), Aatk (apoptosis), Dffa (apoptosis), Itgb1 (cell adhesion), Vcam1 (cell adhesion), Fkbp5 (protein folding), BDNF (neuron survival) were restored to the normal one by the treatment of Boshimgeonbi-Tang.
Kim, SeungMo;Lee, Chang Hyeong;Park, Soo Jin;Kang, Su Jin;Song, Chang Hyun;Han, Chang Hyun;Ku, Sae Kwang;Lee, Young Joon
Journal of Society of Preventive Korean Medicine
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v.18
no.2
/
pp.89-100
/
2014
Objective : The co-administration effects of Gongjindan (GJD) on the pharmacokinetics (PK) of sorafenib were observed as a process of the comprehensive and integrative medicine. Methods : After sorafenib treatment, GJD was administered within 5 min. The plasma were collected at 30min before administration, 30min, 1, 2, 3, 4, 6, 8 and 24hrs after end of GJD treatment, and plasma concentrations of sorafenib were analyzed using LC-MS/MS methods. PK parameters of sorafenib ($T_{max}$, $C_{max}$, AUC, $t_{1/2}$ and $MRT_{inf}$) were analysis as compared with sorafenib single administered rats. Results : The absorption of sorafenib were significantly increased at 30min, 1, 6 and 6hrs after co-administration with GJD as compared with sorafenib single treated rats. Accordingly, the $AUC_{0-t}$ (47.20%) of sorafenib was significantly increased but $t_{1/2}$ (-30.63%) and $MRT_{inf}$ (-34.11%) in co-administered rats were non-significantly decreased. These findings are considered as direct evidences that GJD increased the oral bioavailability of sorafenib through increase of the absorption, when they co-administered within 5min. Conclusion : Based on the results, co-administration of GJD increased the oral bioavailability of sorafenib through increase of the gastrointestinal absorption. It is considered that the more detail pharmacokinetic studies should be tested to conclude the effects of GJD on the pharmacokinetics of sorafenib, when they were co-administered, like the effects after co-administration with reasonable intervals considering the $T_{max}$ of sorafenib (about 3.5hr-intervals) and after repeated co-administrations.Hence, concomitant uses of GJD with sorafenib may require close monitoring for potential drug interactions.
Purpose: The purpose of this study is to delineate the optimal time of venous revascularization for preventing the flap necrosis due to venous occlusion, and to clarify the usefulness of tissue oxygen pressure ($TcpO_2$) in the determination of the point of time for venous revascularization. Methods: Thirty-six, $3{\times}3\;cm$ sized epigastric island flap was elevated in left abdomen of male Sprague-Dawley rat weighing 250 gram. Flaps were randomly assigned to six groups of six flaps according to the duration of venous occlusion with microvascular clamp; 10 minutes in the group I as the control, 60 minutes in the group II, 2 hours in the group III, 3 hours in the group IV, 4 hours in the group V, and 6 hours in the group VI, respectively. Just before removal of clamp after flap was reposed in situ, the ratio of $TcpO_2$ (tissue oxygen pressure) of the island flap to that of right abdomen was calculated in each group, and tissue specimen was harvested from the distal area of the flap for histological evaluation of vascular change. Five days later, survival area of the flap was estimated, and evaluated the correlation between the tissue oxygen pressure and the rate of flap survival. Results: The $TcpO_2$ and the survival rate of flap were decreased proportionally with the duration of venous occlusion. The ratio of the $TcpO_2$ of the flap is decreased abruptly to below sixty percentile compared to the $TcpO_2$ of normal tissue, and the survived area of the flap is decreased to nine-tenth of the designed size after three hours of total venous occlusion. Histologically, the number of congested vessels was increased according to venous occluded time, and proportionally increased after 3-hours of occlusion significantly. Conclusion: There is a close correlation between the $TcpO_2$ and the survival rate of flaps according to the duration of venous occlusion. Therefore, the $TcpO_2$ represents the hemodynamic changes within the flap, and thought to be an alternative effective tool in the flap monitoring for venous revascularization.
This study was performed to investigate the growth rate, hematological and serological changes of the rats when they were fed with the high(at diets supplemented with or without chitosan for five weeks. Twenty-four Sprague-Dawley male rats($235.7{\pm}10.7g$ of body weight) were randomly divided into three groups control group(C) and two treatment groups. Rats in the control group were fed with the high-fat diet containing 10% lard, 1% cholesterol and 0.5% sodium cholate(w/w) which was modified from the formula of the American Institute of Nutrition-76(AIN-76) diet. Rats in treatment groups were red with above diet supplemented with 2.5% of chitosan(CS-2.5) or 5.0% chitosan(CS-5) on the weight to weight basis, respectively. The supplementation of chitosan did not induce any significant difference on the final body weight, gain of body weight and amount of feed intake of rats in between control and treatment groups but the feed efficiency of rats in CS-5 was lower than that of rats in C(p<0.05). The hemoglobin concentrations and hematocrit values showed no significant differences among groups. In addition the values of glucose concentration, total protein, albumin, globulin and albumin/globulin(A/G) ratio showed no significant differences among groups. The values of total cholesterol and low density lipoprotein-cholesterol(LDL-C) in sera of rats in CS-5 were lower than those in both C and CS-2.5(p<0.01). The values of high density lipoprotein-cholesterol (HDL-C) in sera of rats in CS-5 were higher than in both in C and CS-2.5(p<0.05). The values of atherogenic index(AI) of rats in CS-5 were the lowest among groups(p<0.01). AI of CS-2.5 were lower than that or C(p<0.05). The values of triglyceride in sera of rats showed no significant differences among groups. The values of AST in sera of rats in CS-2.5 were lower than those in both C and CS-5(p<0.05). However ALT values showed no significant differences among groups. Therefore the supplementation of chitosan to high fat diet reduced effectively the serum lipid levels such as total cholesterol, LDL-C and triglycerides which were regarded as to cause the cardiovascular diseases moreover it elevated effectively HDL-C value which was regarded protect cardiovascular diseases.
This study was designed to observe the effect of hot water soluble polysaccharides extract(PS) from Lentinus edodes on the enzyme activities related with hepatic function and peroxidation in the rats fed better yellow. The four groups of male SD rats were fed with the diets contained 15% casein(basal diet; NO group), added butter yellow(BO group) or /and PS(NP, BP group) for 6 weeks. The activities of ${\gamma}$-GTP and GPT in BP were significantly lower compared with BO. The activities of glutathione peroxidase, catalase and lactate dehydrogenase were not significantly different between NP and NO, while those activities were significantly lower value in BP than BO. The activities of glutathione S-transferase of the microsomal and cytosol fractions were significantly lower in BP than in BO. The contents of glutathione and malondialdehyde in the liver were considerably low value in BP. In a view of these results the PS of Lentinus edodes prevents the lipid peroxidation and diminishes the liver toxicity caused with better yellow. The superoxide dismutase activity in cytosolic fraction of liver was not found any effect in all groups. But hepatic function enzyme activities such as catalase and glutathione peroxidase, LDH activities were remarkably decreased in the groups 2(basal diet + PS) and the ${\gamma}$-GTP, GOT and GPT activities, too. In liver, the contents of glutathione decreased by PS supplementation but HDL-cholesterol and total cholesterol ratio in plasma decreased at the groups 3, 4. The ${\gamma}$-GTP, GOT and GPT in plasma were remarkably higher in the rats fed the p-DAB than the control group, too. But above enzyme activities significantly decreased in the groups fed PS.
Kim, Soung-Min;Lee, Jong-Ho;Jo, Joung-Ae;Lee, Seung-Cheol;Lee, Suk-Keun
Journal of the Korean Association of Oral and Maxillofacial Surgeons
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v.31
no.5
/
pp.440-453
/
2005
Objectives : To develop a bioactive membrane for guided bone regeneration (GBR), the biocompatibility and bone regenerating capacity of the cellulose membrane obtained from the Ascidians squirt skin were evaluated. Materials and methods : After processing the pure cellulose membrane from the squirt skin, the morphological study, amino acid analysis and the immunoreactivity of the cellulose membrane were tested. Total eighteen male Spraque-Dawley rats (12 weeks, weighing 250 to 300g) were divided into two control (n=8) and another two experimental groups (n=10). In the first experimental group (n=5), the cellulose membrane was applicated to the 8.0 mm sized calvarial bone defect and the same sized defect was left without cellulose membrane in the first control group (n=4). In the another experimental group (n=5), the cellulose membrane was applicated to the same sized calvarial bone defect after femoral bone graft and the same sized defect with bone graft was left without cellulose membrane in the another control group (n=4). Each group was sacrificed after 6 weeks, the histological study with H&E and Masson trichrome stain was done, and immunohistochemical stainings of angiogenin and VEGF were also carried out. Results : The squirt skin cellulose showed the bio-inductive effect on the bone and mesenchymal tissues in the periosteum of rat calvarial bone. This phenomenon was found only in the inner surface of the cellulose membrane after 6 weeks contrast to the outer surface. Bone defect covered with the bioactive cellulose membrane showed significantly greater bone formation compared with control groups. Mesenchymal cells beneath the inner surface of the bioactive cellulose membrane were positive to the angiogenin and VEGF antibodies. Conclusion : We suppose that there still remains extremely little amount of peptide fragment derived from the basement membrane matrix proteins of squirt skin, which is a kind of anchoring protein composed of glycocalyx. This composition could prevent the adverse immunological hypersensitivity and also induce bioactive properties of cellulose membrane. These properties induced the effective angiogenesis with rapid osteogenesis beneath the inner surface of cellulose membrane, and so the possibilities of clinical application in dental field as a GBR material will be able to be suggested.
The study was designed to observe the effect of blend fat calculated from the foods consumed in Korean with those of perilla oil, beef tallow and corn oil on colonic mucosal phospholipid fatty acid composition and the levels of TXB2 and diacylglycerol (DAG) which were known as biomarkers for cancer. Male Sprague Dawley rats, at 7 weeks of age, were divided into control and 1, 2-dimethylhydrazine (DMH)-treated group, and each group was subdivided into four groups. The experimental diets contained one of four dietary fats, blend fat (BF), perilla oil(PO), beef tallow (BT) or corn oil (CO), at 15% (w/w) level. At the same time, each rat was injected with saline for control group or DMH twice a week for 6 weeks to give total dose of 180mg/kg body weight. DMH injection, regardless of the type of dietary fats, significantly increased the levels of PGE2 and TXB2 in colonic mucosal layer compared to control (p<0.01). However, the level of eicosanoids was influenced by the types of dietary fats in both control and DMH group. In control groups, colonic mucosal level of TXB2 was higher in beef tallow group, but lower in perilla oil group compared to that of blend fat (p<0.01). In DMH groups, the level of TXB2 was higher in beef tallow and corn oil groups(p<0.05). The level of PGE2 showed the same trends with TXB2 and beef tallow most significantly increased the level of PGE2. DMH treatment did not influence on tissue fatty acid profile, which was directly reflected by dietary fatty acid composition. Proportions of C18 : 2 in colonic mucosal phospholipid well reflected dietary level of C18 : 2 showing the order CO>BF>PO>BT. The precentage of arachidonic acid(AA) in mucosal phospholipid was the highest by CO adn BT groups and the lowest by PO group. The incorporation of $\alpha$-linolenic acid in colonic mucosal phospholipid in perilla oil group was negatively correlated to the content of AA. Dietary level of C18 : 2 might not be the only controlling factor for the production of eicosanoids in colonic mucosa layer and might function with $\omega$3 fatty acids. The level of DAG was significanlty lower in PO group than that of BT group. Therefore, $\omega$3 $\alpha$-linolenic acid rich perilla oil could be very important dietary sourec in controlling eicosanoid production DAG level in cloln and recommenced to use more often in meal preparation to reduce the risk factor against colon cancer.
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