• The Korean Journal of Physiology and Pharmacology
• /
• v.24 no.5
• /
• pp.395-402
• /
• 2020

This study has investigated the effect of a potent bioflavonoid, troxerutin, on diabetes-induced changes in pro-inflammatory mediators and expression of microRNA-146a and nuclear factor-kappa-B (NF-κB) signaling pathway in aortic tissue of type-I diabetic rats. Male Wistar rats were randomly divided into four groups (n = 6/each): healthy, healthy-troxerutin, diabetic, and diabetic-troxerutin. Diabetes was induced by streptozotocin injection (60 mg/kg; intraperitoneally) and lasted 10 weeks. Troxerutin (150 mg/kg/day) was administered orally for last month of experiment. Inflammatory cytokines IL-1β, IL-6, and TNF-α, as well as intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule (VCAM), cyclooxygenase-II (COX-II), and inducible-nitric oxide synthase (iNOS) were measured on aortic samples by enzyme-linked immunosorbent assay. Gene expressions for transcription factor NF-κB, interleukin-1 receptor-associated kinase-1 (IRAK-1), TNF receptor-associated factor-6 (TRAF-6), and microRNA-146a were determined using real-time polymerase chain reaction. Ten-week diabetes significantly increased mRNA levels of IRAK-1, TRAF-6, NF-κB, and protein levels of cytokines IL-1β, IL-6, TNF-α, adhesion molecules ICAM-1, VCAM, and iNOS, COX-II, and decreased expression of microRNA-146a as compared with healthy rats (p < 0.05 to p < 0.01). However, one month treatment of diabetic rats with troxerutin restored glucose and insulin levels, significantly decreased expression of inflammatory genes and pro-inflammatory mediators and increased microRNA level in comparison to diabetic group (p < 0.05 to p < 0.01). In healthy rats, troxerutin had significant reducing effect only on NF-κB, TNF-α and COX-II levels (p < 0.05). Beside slight improvement of hyperglycemia, troxerutin prevented the activation of NF-κB-dependent inflammatory signaling in the aorta of diabetic rats, and this response may be regulated by microRNA-146a.

• Korean Journal of Acupuncture
• /
• v.35 no.2
• /
• pp.91-97
• /
• 2018

Objectives : This study was performed to investigate immune regulatory effects of the pharmacopuncture with MOK on hyperthyroid rats. Methods : The experimental hyperthyroidism was prepared by the intraperitoneal injection of L-thyroxine(LT4, 0.5 mg/kg) once daily for 2 weeks in Sprague-Dawley(SD) rats. The pharmacopuncture with MOK extract(MOK pharmacopuncture) at doses of 0.3 or 3 mg/kg was injected on acupuncture points in the thyroid glands of hyperthyroid rats once a day for 2 weeks. Propylthiouracil(PTU, 10 mg/kg) as a reference group was subcutaneously injected into the dorsal neck. We measured the levels of $IFN-{\gamma}$ and IL-4 in the sera of rats using enzyme-linked immunosorbant assay(ELISA) and determined the expression of $IFN-{\gamma}$, IL-4, IL-10, and Foxp3 in spleen tissues by reverse transcriptase-polymerase chain reaction(RT-PCR). Results : The treatment of MOK pharmacopuncture in hyperthyroid rats significantly decreased the serum levels of Th1 cytokine, $IFN-{\gamma}$(p<0.01 for MOK 0.3 mg/kg, p<0.05 for MOK 3 mg/kg, and p<0.05 for PTU) and significantly increased the levels of Th2 cytokine, IL-4(p<0.05 for MOK 0.3 mg/kg, p<0.001 for MOK 3 mg/kg, and p<0.05 for PTU) compared to control group. Also, the MOK pharmacopuncture significantly increased IL-4 expression(p<0.05 for MOK 3 mg/kg, and p<0.05 for PTU), IL-10(p<0.05 for MOK 3 mg/kg, and p<0.01 for PTU), and Foxp3(p<0.01 for MOK 0.3 mg/kg, p<0.05 for MOK 3 mg/kg and p<0.01 for PTU) in spleen tissues of hyperthyroid rats compared to control group. Conclusions : Our results suggest that MOK pharmacopuncture can help to ameliorate the pathological progression of hyperthyroidism by regulation of the Th1/Th2 imbalance.

• Journal of Nutrition and Health
• /
• v.23 no.6
• /
• pp.418-426
• /
• 1990

This study examines the effects of choline deficiency and 2-acetylaminofluorene(2-AAF) on the lipid peroxide values, glucose 6-phosphatase(G6Pase) and glutathione S-transferase (GST) activities in rats fed different dietary fats. Weanling Sprague Dawley male rats fed the diets containing 15% beef tallow or 15% corn oil with vitamin fortification mixture or choline free vitamin mixture for 10 weeks. At 3th and 5th week, 2-AAF was injected twice each week intraperitoneally. Total 2-AAF injection was four times. 2-AAF and choline deficiency increased lipid peroxidation in corn oil groups, so the role of 2-AAF and choline deficiency in lipid peroxidation was more important in corn oil groups than beef tallow groups. G6Pase activities tended to be decreased by 2-AAF in choline deficient groups, and in corn oil groups, the enzyme activities were decreased significantly in all subgroups compaired to beef tallow groups. GST activities were increased by 2-AAF in beef tallow groups and choline deficiency in corn oil groups, and might defence against carcinogen metabolism and lipid peroxidation.

• Nutrition Research and Practice
• /
• v.13 no.6
• /
• pp.473-479
• /
• 2019

BACKGROUND/OBJECTIVES: Anti-inflammatory and antioxidative activities of luteolin and luteolin-7-O-glucoside were compared in galactosamine (GalN)/lipopolysaccharide (LPS)-induced hepatitic ICR mice. MATERIALS/METHODS: Male ICR mice (6 weeks old) were divided into 4 groups: normal control, GalN/LPS, luteolin, and luteolin-7-O-glucoside groups. The latter two groups were administered luteolin or luteolin-7-O-glucoside (50 mg/kg BW) daily by gavage for 3 weeks after which hepatitis was induced by intraperitoneal injection of GalN and LPS (1 g/kg BW and $10{\mu}g/kg\;BW$, respectively). RESULTS: GalN/LPS produced acute hepatic injury by a sharp increase in serum AST, ALT, and $TNF-{\alpha}$ levels, increases that were ameliorated in the experimental groups. In addition, markedly increased expressions of cyclooxygenase (COX)-2 and its transcription factors, nuclear factor $(NF)-{\kappa}B$ and activator protein (AP)-1, were also significantly attenuated in the experimental groups. Compared to luteolin-7-O-glucoside, luteolin more potently ameliorated the levels of inflammatory mediators. Phase II enzymes levels and NF-E2 p45-related factor (Nrf)-2 activation that were decreased by GalN/LPS were increased by luteolin and luteolin-7-O-glucoside administration. In addition, compared to luteolin, luteolin-7-O-glucoside acted as a more potent inducer of changes in phase II enzymes. Liver histopathology results were consistent with the mediator and enzyme results. CONCLUSION: Luteolin and luteolin-7-O-glucoside protect against GalN/LPS-induced hepatotoxicity through the regulation of inflammatory mediators and phase II enzymes.

• Archives of Pharmacal Research
• /
• v.24 no.6
• /
• pp.557-563
• /
• 2001

Oral tolerance is thought to play a role in preventing allergic responses and immune-mediated diseases. An improved mouse model of the oral tolerance to Japanese cedar pollen (JCP) as antigen was developed in order to detect induction of the tolerance, and the immunological characteristics of this model were also elucidated. Oral tolerance was induced by C3H/ HeN mice given an oral administration of 10 mg JCP 7 days before immunization with an i.p. injection of 0.1 mg JCP in complete Freunds adjuvant (CFA). The effects of oral JCP on systemic immunity were assessed by enzyme-linked immunosorbent assay (ELISA) of immunoglobulin (Ig) levels in serum collected on day 7 or 14 after immunization. Oral tolerance to JCP was adequately induced on day 7 after immunization and was more effective in C3H/HeN mice than in BALB/c mice. The tolerance was primarily concerned with the decreased serum levels of antigen-specific IgG. In these mice, oral administration of JCP also suppressed various immune responses to the antigen including delayed-type hypersensitivity (DTH), total Igl level and anti-JCP IgGl level. The suppression of these immune responses by the oral antigen was associated with a significant reduction in interleukin-4 (IL-4) production. These findings therefore indicate that this C3H/HeN mice model has potential use in detecting the induction of oral tolerance by JCP and suggest that this tolerance model may be effective in the treatment and prevention of allergic responses caused by the antigen.

• Clinical and Experimental Reproductive Medicine
• /
• v.48 no.3
• /
• pp.245-254
• /
• 2021

Objective: In humans, polycystic ovary syndrome (PCOS) is an androgen-dependent ovarian disorder. Aberrant gene expression in folliculogenesis can arrest the transition of preantral to antral follicles, leading to PCOS. We explored the possible role of altered gene expression in preantral follicles of estradiol valerate (EV) induced polycystic ovaries (PCO) in a mouse model. Methods: Twenty female balb/c mice (8 weeks, 20.0±1.5 g) were grouped into control and PCO groups. PCO was induced by intramuscular EV injection. After 8 weeks, the animals were killed by cervical dislocation. Blood serum (for hormonal assessments using the enzyme-linked immunosorbent assay technique) was aspirated, and ovaries (the right ovary for histological examinations and the left for quantitative real-time polymerase) were dissected. Results: Compared to the control group, the PCO group showed significantly lower values for the mean body weight, number of preantral and antral follicles, serum levels of estradiol, luteinizing hormone, testosterone, and follicle-stimulating hormone, and gene expression of TGFB1, GDF9 and BMPR2 (p<0.05). Serum progesterone levels were significantly higher in the PCO animals than in the control group (p<0.05). No significant between-group differences (p>0.05) were found in BMP6 or BMP15 expression. Conclusion: In animals with EV-induced PCO, the preantral follicles did not develop into antral follicles. In this mouse model, the gene expression of TGFB1, GDF9, and BMPR2 was lower in preantral follicles, which is probably related to the pathologic conditions of PCO. Hypoandrogenism was also detected in this EV-induced murine PCO model.

• Journal of Veterinary Science
• /
• v.22 no.1
• /
• pp.8.1-8.11
• /
• 2021

Background: Porcine circovirus type 2 (PCV2) is an important infectious pathogen implicated in porcine circovirus-associated diseases (PCVAD), which has caused significant economic losses in the pig industry worldwide. Objectives: A suitable viral vector-mediated gene transfer platform for the expression of the capsid protein (Cap) is an attractive strategy. Methods: In the present study, a recombinant adeno-associated virus 8 (rAAV8) vector was constructed to encode Cap (Cap-rAAV) in vitro and in vivo after gene transfer. Results: The obtained results showed that Cap could be expressed in HEK293T cells and BABL/c mice. The results of lymphocytes proliferative, as well as immunoglobulin G (IgG) 2a and interferon-γ showed strong cellular immune responses induced by Cap-rAAV. The enzyme-linked immunosorbent assay titers obtained and the IgG1 and interleukin-4 levels showed that humoral immune responses were also induced by Cap-rAAV. Altogether, these results demonstrated that the rAAV8 vaccine Cap-rAAV can induce strong cellular and humoral immune responses, indicating a potential rAAV8 vaccine against PCV2. Conclusions: The injection of rAAV8 encoding PCV2 Cap genes into muscle tissue can ensure long-term, continuous, and systemic expression.

• Journal of the Korean Society of Radiology
• /
• v.13 no.3
• /
• pp.439-444
• /
• 2019

In this study, the radiation protection effects of selenium, known as a powerful antioxidant, were studied. After 14 days of oral injection of selenium into the rat, a full body irradiation of 10 Gy was carried out. And after 1 day, 3.5 day, 7 day and 21 day, we observed blood cell components and superoxide dismutase(SOD) and small intestine changes. Compared to irradiation groups, there was a significant protection effect of reducing the hematopoietic immune system damage in the irradiated group after selenium administration(p<0.05). Then, selenium is a valid ingredient that increases the activity of the superoxide Dismutase(SOD), and it is confirmed that it has an effect of inhibiting apoptosis expression of small intestinal cells by irradiation. Based on these results, selenium is considered to be an essential ingredient for protecting living things from radiation.

• Journal of Ginseng Research
• /
• v.43 no.4
• /
• pp.618-624
• /
• 2019

Background: Ginsenoside Re (Re) is one of the major components of Panax ginseng Meyer. Ginsenoside $Rk_3$ ($Rk_3$) is a secondary metabolite of Re. The aim of this study was to investigate and compare the effects and underlying mechanisms of Re and $Rk_3$ on cyclophosphamide-induced myelosuppression. Methods: The mice myelosuppression model was established by intraperitoneal (i.p.) injection of cyclophosphamide. Peripheral blood cells, bone marrow nucleated cells, and colony yield of hematopoietic progenitor cells in vitro were counted. The levels of erythropoietin, thrombopoietin, and granulocyte macrophage colony-stimulating factor in plasma were measured by enzyme-linked immunosorbent assay. Bone marrow cell cycle was performed by flow cytometry. The expression of apoptotic protein bcl-2, bax, and caspase-3 was detected by Western blotting. Results: Both Re and $Rk_3$ could improve peripheral blood cells, bone marrow nucleated cell counts, thymus index, and spleen index. Furthermore, they could enhance the yield of colonies cultured in vitro and make the levels of granulocyte macrophage colony-stimulating factor, erythropoietin, and thrombopoietin normal, reduce the ratio of $G_0/G_1$ phase cells, and increase the proliferation index. Finally, Re and $Rk_3$ could upregulate the expression of bcl-2, whereas they could downregulate the expression of bax and caspase-3. Conclusion: Re and $Rk_3$ could improve the hematopoietic function of myelosuppressed mice. The effect of $Rk_3$ was superior to that of Re at any dose. Regulating the levels of cytokines, promoting cells enter the normal cell cycle, regulating the balance of bcl-2/bax, and inhibiting the expression of caspase-3 may be the effects of Re and $Rk_3$ on myelosuppression.

• Clinical and Experimental Reproductive Medicine
• /
• v.48 no.2
• /
• pp.105-110
• /
• 2021

Objective: Uropathogenic Escherichia coli is known to cause urinary tract infections, and the endotoxin (lipopolysaccharide [LPS]) of this bacterium may cause deficiencies of sperm quality and morphology. In the present study, the effects of LPS on mouse sperm were studied, and the levels of interleukin (IL)-17A and possible changes in testis tissue were evaluated. Methods: LPS of uropathogenic E. coli was extracted using the methanol-chloroform method, followed confirmation using sodium dodecyl sulfate-polyacrylamide electrophoresis. Purified LPS (100 ㎍/kg) or phosphate-buffered saline was injected intraperitoneally into BALB/c mice for 7 days consecutively in the test and control groups, mice were sacrificed on days 3, 7, and 42 after the first injection. Blood was tested for levels of IL-17A using the enzyme-linked immunosorbent assay method. Testis tissue and sperm were collected from each mouse and were studied according to standard protocols. Results: The mean sperm count and motility significantly decreased (p=0.03) at 3, 7, and 42 days after the injections. The level of IL-17A in the test groups increased, but not significantly (p=0.8, p=0.11, and p=0.15, respectively). Microscopic studies showed no obvious changes in the morphology of the testis tissue; however, significant changes were observed in the cellular parenchyma on day 42. Conclusion: LPS can stimulate the immune system to produce proinflammatory cytokines, resulting in an immune response in the testis and ultimately leading to deficiency in sperm parameters and testis tissue damage. In addition, the presence of LPS could significantly impair sperm parameters, as shown by the finding of decreased motility.