• Journal of Pharmacopuncture
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• v.20 no.1
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• pp.10-17
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• 2017

Objectives: Boswellic acid (BA), a compound isolated from the gum-resin of Boswellia carterii, is a pentacyclic terpenoid that is active against many inflammatory diseases, including cancer, arthritis, chronic colitis, ulcerative colitis, Crohn's disease, and memory impairment, but the mechanism is poorly understood. This study investigated the effects of boswellic acid on spatial learning and memory impairment induced by trimethyltin (TMT) in Wistar rats. Methods: Forty male Wistar rats were randomly divided into 5 groups: Normal group, TMT-administrated rats (8.0 mg/kg, Intraperitoneally, i.p.) and TMT + BA (40, 80 and 160 mg/kg, i.p.)-administrated rats. BA was used daily for 21 days. To evaluate the cognitive improving of BA, we performed the Morris water maze test. Moreover, to investigate the neuroprotective effect of BA, we determined the acetylcholinesterase (AchE) activity, the malondialdehyde (MDA) level as a marker of lipid peroxidation, and the glutathione (GSH) content in the cerebral cortex. Results: Treatment with TMT impaired learning and memory, and treatment with BA at a dose of 160 mg/kg produced a significant improvement in learning and memory abilities in the water maze tasks. Consistent with behavioral data, the activity of AChE was significantly increased in the TMT-injected rats compared to the control group (P < 0.01) whereas all groups treated with BA presented a more significant inhibitory effect against AChE than the TMT-injected animals. In addition, TMT reduced the GSH content and increased the MDA level in the cerebral cortex as compared to the control group) P < 0.01). On the other hand, treatment with BA at 160 mg/kg slightly increased the GSH content and reduced the MDA level in comparison to the TMT-administered group (P < 0.01). Conclusion: The above results suggest that the effect of BA in improving the cognitive function may be mediated through its antioxidant activity.

• CELLMED
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• v.6 no.2
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• pp.11.1-11.7
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• 2016

The aimed of the presence study was to determine the antiulcer potential of virgin coconut oil (VCO), either extracted by wet process (VCO_A) or fermentation process (VCO_B), and to compare their effectiveness against the copra oil (CO) using the HCl/ethanol-induced gastric ulcer model. Earlier, the oils underwent chemical analysis to determine the free fatty acids composition, physicochemical properties and anti-oxidant capability. In the antiulcer study, rats (n=6) were pre-treated orally for 7 consecutive days with distilled water (vehicle), 100 mg/kg ranitidine (positive group) or the respective oils (10, 50, and 100% concentration). One hour after the last test solutions administration on Day 7^th, the animals were subjected to the gastric ulcer assay. Macroscopic and microscopic analyses were performed on the collected rat's stomachs. From the results obtained, the chemical analysis revealed i) the presence of high content of lauric acid followed by myristic acid and palmitic acid in all oils and; ii) the significant (^*p< 0.05) different in anisidine- and peroxide-value, percentage of free fatty acid, total phenolic content and total antioxidant activity among the oils. The animal study demonstrated that all oil possess significant (^*p< 0.05) antiulcer activity with VCO_B being the most effective oil followed by VCO_A and CO. The macroscopic observations were supported by the microscopic findings. Interestingly, all oils were more effective than 100 mg/kg ranitidine (reference drug). In conclusion, coconut oils exert remarkable antiulcer activity depending on their methods of extraction, possibly via the modulation of its antioxidant and anti-inflammatory activity.

• Korean Journal of Veterinary Pathology
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• v.5 no.1
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• pp.23-28
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• 2001

This study was conducted to assess the chemopreventive effects of sodium selenite in the rat medium-term multi-organ bioassay using a DMBDD model (DEN+MNU+BBN+DMH+DHPN). Seventy five,6-week-old, male SD rats were divided into 3 groups. The animals in group 1 received DEN(diethylnitrosamine,100 mg/kg bw, single i.p., in saline), MNU (N-methyl-nitrosourea,20 mg/kg bw, i.p.,4 times for 2 weeks), BBN (N-butyl-N-(4-hydroxybutyl) nitrosamine, 0.2% in drinking water for 2 weeks), DMH (1,2-dimethylhydrazine, 40 mg/kg bw, s.c., in saline.4 times (or 2 weeds), and DHPN (N-bis(2-hydroxy-pro-pal)nitrosamine,0.1% in drinking water for 2 weeks), then were placed on sodium selenite (4 ppm in drinking water) for 22 weeks from weeks 4 to 26. The animals in group 2 were given DMBDD alone. The animals in group 3 were given sodium selenite alone. Animals were sacrificed at week 12 for ACF quantitative analysis and at week 26 for tumor induction. The body weights in the group 1 were significantly decreased compared with those of group 2. The tumor multiplicities of large intestine in the group 1 were significantly decreased compared with those of group 2 (P<0.05). These results indicate that sodium selenite may have a potential as chemopreventive agents of colon carcinogenesis.

• Molecules and Cells
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• v.24 no.2
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• pp.255-260
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• 2007

Bone marrow (BM) derived mesenchymal stem cells (MSC) are pluripotent cells which can differentiate into osteogenic, adipogenic and other lineages. In spite of the broad interest, the information about the changes in BM cell composition, in particularly about the variation of MSC number and their properties in relation to the age of the donor is still controversial. The aim of this study was to investigate the age associated changes in variations of BM cell composition, phenotype and differentiation capacities of MSC using a rat model. Cell populations were characterized by flow cytometry using light scattering parameters, DNA content and a set of monoclonal antibodies. Single cell analysis was performed by conventional fluorescent microscopy. In vitro culture of MSC was established and their phenotype and capability for in vitro differentiation into osteogenic and adipogenic cells was shown. Age related changes in tibiae and femurs, amount of BM tissue, BM cell composition, proportions of separated MSC and yield of MSC in 2 weeks of in vitro culture were found. At the same time, neither change in phenotype no in differentiation capacities of MSC was registered. Age-related changes of the number of MSC should be taken into account whenever MSC are intended to be used for investigations.

• YAKHAK HOEJI
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• v.42 no.2
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• pp.220-228
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• 1998

The effects of herbal medicine on travecular bone area were studied using ovariectomized rat as an animal model of Type I osteoporosis and SAM P6 as that of Type II. We counted red blood cells(RBC), hemoglobin(Hb), and hematocrit(Hct) using Couter`sR method. Each traditional boiling water extract of Achyrathis Radix, Psoraleae Fructus, Rehmanniae Radix Preparat, and Cornii Fructus and a systemic water extract of Astragali Ractiex was given 5g/kg/day, p.o., for 30 days in a group of 4-5 ovariectormized rats. One ml of blood was taken by tail vein at day 0, 7, 14, 21, and 30 days after administration of the extract. The traditional hot water extract of Cervi parvumn Corni (Cervi) was given the same dose as described above for 14 days in a group of 10 SAM P6 mice and systemic water extract of Astragali Radix was administered as the same dose as above for 30 days in 10 SAM P6 mice. Travecular bone area was measured 5 mcm decalcified and stained thin bone slice by image analysis using a digitalizer. In Type I, ovariectomized rats, administration of Astragali Radix, Rhemanniae Radix Preparat, and Corni Fructus decreased in RBC, Hb and Hct. In Type II, administration of Cervi increased in RBC and Hct and that of Astragali Radix was also elevated RBC. In Type I, any administration of herbal medicine used in this study did not elevate travecular bone area significantly except Corni Fructus showed a trend of increase in travecular bone area. However, Type II, Cervi and Astragali Radix increased in both mean and total travecular bone area. Thus, there are significant difference in response of herbal medicine in different types of osteoporosis.

• Korean Journal of Clinical Pharmacy
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• v.3 no.1
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• pp.31-43
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• 1993

The influence of phenobarbital(PB) pretreatment(75mg/kg/day, Lp. for 4 days) on the hepatic clearance of indocyanine green(ICG) as a model compound of organic anionic drugs was investigated in rats in order to elucidate the relative contributions of change in the hepatic blood flow versus increase in the hepatic intrinsic activity to remove ICG due to PB pretreatment. ICG(1mg/kg) was injected single bolus via femoral or portal vein to the control and the PB-pretreated rats. The initial hepatic uptake clearance$(V_{d.c.}K_{12})$ obtained from plasma concentration-time data was increased by $38.4\% in the PB-pretreated rats, which may be due to the increased hepatic blood flow by PB pretreatment. Using a pharmacokinetic approach, hepatic blood flows were estimated of 67.5ml/min/kg in control rats and 91.9ml/min/kg in PB-pretreated rats. They were in good agreement with other's blood flow estimates observed experimentally. It may be concluded that the $38\%$ increased initial hepatic uptake clearance of ICG was due to the $36\%$ increased hepatic blood flow with phenobarbital, and that the increased hepatic blood flow and the activated hepatic intrinsic clearance with phenobarbital contributed to $49\%\;and\;51\%$ of the increased systemic clearance of ICG, respectively.

• International Journal of Oral Biology
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• v.40 no.2
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• pp.71-77
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• 2015

The activation of glial cells in the spinal cord has been contribute to the initiation and maintenance of pain facilitation induced by peripheral inflammation and nerve injury. The present study investigated effects of botulinum toxin type A (BoNT-A), injected subcutaneously or intracisternally, on the expression of microglia and astrocytes in rats. Complete Freund's Adjuvant (CFA)-induced inflammation was employed as an orofacial chronic inflammatory pain model. A subcutaneous injection of $40{\mu}L$ CFA into the vibrissa pad was performed under 3% isoflurane anesthesia in SD rats. Immunohistochemical analysis for changes in Iba1 (a microglia marker) and GFAP (an astrocyte marker), were performed 5 days after CFA injection. Subcutaneous injection of CFA produced increases in Iba1 and GFAP expression, in the ipsilateral superficial lamia I and II in the medullary dorsal horn of rats. Subcutaneous treatment with BoNT-A attenuated the up-regulation of Iba1 and GFAP expressions induced by CFA injection. Moreover, intracisternal injection of BoNT-A also attenuated the up-regulated Iba1 and GFAP expressions. These results suggest that the anti-nociceptive action of BoNT-A is mediated by modulation activation of glial cells, including microglia and astrocyte.

• Molecules and Cells
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• v.37 no.4
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• pp.322-329
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• 2014

N-acetylglucosamine kinase (GlcNAc kinase or NAGK; EC 2.7.1.59) is highly expressed and plays a critical role in the development of dendrites in brain neurons. In this study, the authors conducted structure-function analysis to verify the previously proposed 3D model structure of GlcNAc/ATP-bound NAGK. Three point NAGK mutants with different substrate binding capacities and reaction velocities were produced. Wild-type (WT) NAGK showed strong substrate preference for GlcNAc. Conversion of Cys143, which does not make direct hydrogen bonds with GlcNAc, to Ser (i.e., C143S) had the least affect on the enzymatic activity of NAGK. Conversion of Asn36, which plays a role in domain closure by making a hydrogen bond with GlcNAc, to Ala (i.e., N36A) mildly reduced NAGK enzyme activity. Conversion of Asp107, which makes hydrogen bonds with GlcNAc and would act as a proton acceptor during nucleophilic attack on the ${\gamma}$-phosphate of ATP, to Ala (i.e., D107A), caused a total loss in enzyme activity. The overexpression of EGFP-tagged WT or any of the mutant NAGKs in rat hippocampal neurons (DIV 5-9) increased dendritic architectural complexity. Finally, the overexpression of the small, but not of the large, domain of NAGK resulted in dendrite degeneration. Our data show the effect of structure on the functional aspects of NAGK, and in particular, that the small domain of NAGK, and not its NAGK kinase activity, plays a critical role in the upregulation of dendritogenesis.

• Molecules and Cells
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• v.41 no.2
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• pp.93-102
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• 2018

Discoidin domain receptor 1 (DDR1) is involved in tumorigenesis and angiogenesis. However, its role in lymphangiogenesis has been unknown. Here, we tested whether downregulation of DDR1 expression by miR-199a/b can suppress lymphangiogenesis. We also aimed to identify miRNA target site(s) in the 3' untranslated region (UTR) of DDR1. Transfection with miR-199a/b-5p mimics reduced expression of DDR1 and tube formation in primary human dermal lymphatic endothelial cells, whereas miR-199a/b-5p inhibitors showed the opposite effects. Critically, injection of miR-199a/b-5p mimics suppressed DDR1 expression and lymphangiogenesis in a corneal alkali-burn rat model. The three well-conserved seed matched sites for miR-199a/b-5p in the DDR1 3'-UTR were targeted, and miRNA binding to at least two sites was required for DDR1 inhibition. Our data suggest that DDR1 promotes enhanced lymphangiogenesis during eye injury, and miR-199a/b-5p suppresses this activity by inhibiting DDR1 expression. Thus, this miRNA may be useful for the treatment of lymphangiogenesis-related eye diseases.

• Biomolecules & Therapeutics
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• v.3 no.4
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• pp.279-287
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• 1995

This study examined the anti-cancer effects of diallyl sulfide(DAS) and/or diallyl disulfide(DDS), major components of garlic oil, with the DEN-PH model in rats, by the numbers and areas per cm$^2$ of induced glutathion S-transferase placental form(GST-P) positive foci and silver-stained nucleolar organizer regions(Ag-NORs) counts per nuclei in liver as indicator. Sprague-Dawley(SD) rats were given the diethylnitrosamine(DEN, 200 mg/kg, i.p.) as initiator and 2 weeks later, in experiment 1, rats were treated with DAS(200 mg/kg, i.g.) and/or DDS(50 mg/kg, i.g.) for 6 weeks, respectively and concomitantly and also were given the same dose of DAS and/or DDS prior to DEN treatment for 2 weeks, and in experiment II, rats were treated with potential cancer promoter, 2-acetylaminofluorene (2-AAF, 20 mg/kg, i.g.). The DAS and/or DDS were treated prior to 2-AAF for 8 weeks, respectively and concomitantly. Then the anti-promoting effects of DAS and/or DDS were assessed. All rats were subjected to the two-thirds partial hepatectomy(PH) at week 3 and sacrificed at week 8. In experiment I, DAS and/or DDS treatment only prior to DEN showed inhibition of the development of GST-P positive foci. In experiment II, DAS and/or DDS treatment prior to 2-AAF promotion showed obvious inhibition of the development of GST-P positive foci in numbers and areas and AgNORs counts. In conclusion, We found DAS and/or DDS had the preventive effects on the hepatocarcinogenesis in rats and the concomitant treatment had some additive effects compared with the each treatment and AgNORs counts correlated well with the preneoplastic hepatic lesion.