• Journal of Acupuncture Research
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• v.40 no.2
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• pp.135-142
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• 2023

Background: This study aimed to investigate hyperuricemia, renal inflammation, and xanthine oxidase (XO) activity improvement in a rat model treated with Scutellaria baicalensis extract (SBE). Methods: The rats were divided into 4 groups (n = 5 each), including sham, potassium oxonate (PO) injected hyperuricemia (control group), PO + 10 mg/kg allopurinol administrated (allopurinol group), and a PO + 50 mg/kg SBE administrated (SBE group), to investigate the effectiveness and molecular mechanisms of SBE. The effects of SBE on PO-induced hyperuricemia rats, renal inflammation, and XO activity were measured. Body weight and organ index of the kidney and liver were measured in PO-induced hyperuricemia rats, and serum uric acid level was extracted from whole blood and was measured. Renal inflammation was observed under a microscope after sections. XO activity was measured by liver tissue and serum XO levels. Results: Organ indexes of the kidney and liver in rats were significantly decreased in the allopurinol group than in the control group and with no significant difference in the SBE group. A PO injection for 5 days significantly increased serum uric acid levels in the control group compared to the sham group. Meanwhile, the SBE and allopurinol groups have significantly decreased serum uric acid levels compared to the control group. The SBE group revealed effectively improved renal histopathological changes compared to the control group. The XO inhibitor, allopurinol, significantly decreased XO activity. Additionally, SBE significantly lowered XO activity in rats. Conclusion: SBE can be used as an effective treatment for gout in the future.

• Korean Journal of Animal Reproduction
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• v.17 no.2
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• pp.165-171
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• 1993

While ornithine decarboxylase (ODC) is considered a key enzyme in the biosynthesis of polyamines, difluoromethylornithine(DFMO) acts as an inhibitor of polyamine synthesis. Cycling crossbred gilts were randomly assigned to one of two (treatment and control) groups (6/group). An indwelling silicone catheter was surgically implanted in the jugular vein of each animal. DFMO was dissolved in saline(200 mg/ml) and adminstered by i. m. injection at a dose of 80 mg/kg/day. The control group received an equivalent volume saline injection. DFMO was injected 3 times daily(08:00. 16:00. 24:00h) from day 16 of estrous cycle to 21 or until estrus. Once daily blood samples (10ml) were taken from day 14 until two days after the last DFMO treatment. Window blood samples were collected every 15 min for 8 h (from 08:00 to 16:00h) starting on day 16 and continuing until day 21 from one gilt per day. Serum progesterone (P$_4$), estradiol (E$_2$), LH and FSH were measured. Typical concentration profiles for P$_4$ and E$_2$ were seen during the follicular phase regardless of DFMO treatment. Injection of DFMO suppressed the preovulatory LH concentration in the serum(p<0.01) while having no effect on FSH profile. The present results indicate that DFMO had an inhibitory effect on LH secretion in the pig, but did not affect PI, E2 or FSH release.

• BMB Reports
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• v.35 no.2
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• pp.172-177
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• 2002

We previously reported that cholesteryl ester transfer protein (CETP) inhibitory peptides (designated $P_{28}$ and $P_{10})$ have anti-atherogenic effects in hypercholesterolemic rabbits (Biochim. Biophys. Acta (1998) 1391, 133-144). To further investigate those effects, we studied rabbit plasma that was collected after 30 h of a $P_{28}$ or $P_{10}$ injection. We found that there is a strong correlation between the in vivo CETP inhibition effects and alterations of lipoprotein particle size distribution in rabbit plasma, as determined on an agarose gel electrophoresis and gel filtration column chromatography. In vivo effects of the peptide were observed again in C57BL/6 mice that expressed simian CETP. The $P_{28}$ or $P_{10}$ peptide ($7\;{\mu}g/g$ of body weight) that was dissolved in saline was injected subcutaneously into the mice. The $P_{28}$ injection caused the partial inhibition of plasma CETP activity up to 50%, decreasing the total plasma cholesterol concentration by 30%, and increasing the ratio of HD/total-cholesterol concentration by 150% in the CETP-transgenic (tg) mice. The CETP inhibition by the $P_{28}$ or $P_{10}$ made alterations that modulated the size re-distribution of the lipoproteins in the blood stream. Particle size of the very low (VLDL) and low density lipoproteins (LDL) from the peptide-injected group was highly decreased compared to the saline-injected group (determined on the gel filtration column chromatography). In contrast, The HDL particle size of the $P_{28}$-injected group increased compared to the control group (saline-injected). The expression level of the CETP mRNA of the $P_{28}$-injected CETP-tg mouse appeared lower than the saline-injected CETP-tg mouse. These results suggest that the injection of the CETP inhibitory peptide could affect the CETP expression level in the liver by influencing lipoprotein metabolism.

• Journal of Nutrition and Health
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• v.51 no.1
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• pp.14-22
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• 2018

Purpose: Colorectal cancer, which is one of the most commonly diagnosed cancers in developing and developed countries, is highly associated with obesity. The association is largely attributed to changes to western style diets in those countries containing high-fat and high-energy. Luteolin (LUT) is a known potent inhibitor of inflammation, obesity, and cancer. In this study, we investigated the effects of LUT on chemical-induced colon carcinogenesis in high fat diet (HFD)-fed obese mice. Methods: Five-week-old male C57BL/6 mice received a single intraperitoneal injection of azoxymethane (AOM) at a dose of 12.5 mg/kg body weight. Mice were then divided into four groups (n = 10) that received one of the following diets for 11 weeks after the AOM injection: normal diet (ND); HFD; HFD with 0.0025% LUT (HFD LL); HFD with 0.005% LUT (HFD HL). One week after AOM injection, animals received 1~2% dextran sodium sulfate in their drinking water over three cycles consisting of five consecutive days each that were separated by 16 days. Results: Body weight, ratio of colon weight/length, and tumor multiplicity increased significantly in the HFD group compared to the ND group. Luteolin supplementation of the HFD significantly reduced the ratio of colon weight/length and colon tumors, but not body weight. The levels of plasma $TNF-{\alpha}$ and colonic expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 protein increased in response to HFD, but were suppressed by LUT supplementation. Immunohistochemistry analysis also showed that iNOS expression was decreased by LUT. Conclusion: Consumption of LUT may reduce the risk of obesity-associated colorectal cancer by suppression of colonic inflammation.

• Proceedings of the KSAR Conference
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• 2001.03a
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• pp.51-51
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• 2001

Cocaine and amphetamine-regulated transcript (CART) is a satiety factor that is regulated by leptin. It was reported that the mice intracerebroventricularly injected with CART showed behavioral changes resembled with the typical behavioral alterations found in the mice carrying disorders in the brain serotonergic (5-HT) system. Hence, this study was conducted to find out the relationships between CART and 5-HT. We first examined the mRNA levels of CART after the injections of para-chlorophenylalanine (pCPA, 300 mg/kg i.p., single injection or daily for three consecutive days) in the rat brains by in situ hybridization using the mouse CART cDNA probe cloned in our laboratory. Systemic administrations of pCPA, a potent inhibitor of tryptophan hydroxylase, the rate limiting enzyme of 5-HT biosynthesis, acutely depletes the brain 5-HT transporter (5-HTT) in the dorsal raphe nucleus (DRN), which reuptakes terminal 5-HT. Results indicated that the mRNA level of CART significantly decreased in the arcuate nucleus, paraventricular nucleus, and lateral hypothalamic nucleus by three days of daily injection with pCPA with no noticeable change detected 24 hrs after the single injection. The message levels of 5-HTT in DRN decreased in both single and three days of injections. Secondly, to investigate whether CART affect to 5-HT, mouse genomic CART gene, which is consist of 3 exons and 2 introns and mouse neurofilament light (NF-L) chain promoter were cloned. Then, we constructed neuron specific expression vector, which was transfected into HeLa cell using lipid-mediated transfection system. Expression of GFP and CART linked to NF-L-chain promoter in the transfected HeLa cell were detected by using fluorescent microscope and RT-PCR. These results confirmed normal expression of DNA constructs in vitro. Then, to increase brain specific expression of CART in vivo transgenic mice carrying CART gene controlled the deleted NF-L-chain promoter were generated by the DNA microinjection into pronuclei of fertilized embryos. Transgenic mice were detected by Southern blot. Further study is necessary to examine CART expression and 5-HTT in these transgenic mice. Therefore, these results suggest that there maybe a positive molecular correlation between CART and 5-HT in responding to the stimuli.

• Journal of the Korea Academia-Industrial cooperation Society
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• v.12 no.1
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• pp.529-536
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• 2011

In this study, we confirmed that the SWRO(Sea Water Reverse Osmosis) production water has more hard corrosiveness than the tap water by fundamental experiment. According to the result, the target of this study was aimed at developing maintenance and anti-corrosion method. In the early stages of the research, batch tests using mild steel coupons and electrochemical experiments were applied to compare the corrosiveness between SWRO production water and the tap water. After then, two corrosion control methods for SWRO production water were applied. Liquid lime($Ca(OH)_2$) and Carbon Dioxide($CO_2$) were inserted and compared with the combination of liquid lime with phosphate corrosion inhibitor and carbon dioxide. The water qualities were evaluated through LSI(Langelier Saturation Index) and proper injection ratio was deduced by the result. Since then, simulated loop system test were performed to evaluate anti-corrosion effect depending on corrosion inhibitors. Subsequently, carbon steel pipes equipped at the loop system were detached for SEM, EDX and XRD analysis to acquire quantitative and qualitative data of the major corrosion products inside the pipes. In conclusion, the controled groups with anti-corrosion techniques applied were effective by appearing 97.4% and 90.9% of improvements in both case of liquid lime and the liquid lime with a phosphate corrosion Inhibitor. furthermore, major components of scale were iron oxides, on the other hand, protective effect of film formation by calcium carbonate($CaCO_3$) could be confirmed.

• IMMUNE NETWORK
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• v.3 no.3
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• pp.201-210
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• 2003

Objective: The role of prostaglandin $E_2$ (PGE2) in the etiopathogenesis of immune and inflammatory diseases has become the subject of recent debate. To determine the role of PGE2 in rheumatoid arthritis (RA), we tested the effect of exogenous PGE2 on the production of cyclooxygenase-2 (COX-2) by rheumatoid synoviocytes. Methods: Fibroblast-like synoviocytes (FLS) were prepared from the synovial tissues of RA patients, and cultured in the presence of PGE2. The COX-2 mRNA and protein expression levels were determined by RT-PCR and Western blot analysis, respectively. The PGE2 receptor subtypes in the FLS were analyzed by RT-PCR. Electrophoretic mobility shift assay (EMSA) was used to measure the NF-${\kappa}B$ binding activity for COX-2 transcription. The in vivoeffect of PGE2 on the development of arthritis was also tested in collagen induced arthritis (CIA) animals. Results: PGE2 ($10^{-11}$ to $10^{-5}M$) dose-dependently inhibited the expression of COX-2 mRNA and the COX-2 protein stimulated with IL-$1{\beta}$, but not COX-1 mRNA. NS-398, a selective COX-2 inhibitor, displayed an additive effect on PGE2-induced COX-2 downregulation. The FLS predominantly expressed the PGE2 receptor (EP) 2 and EP4, which mediated the COX-2 suppression by PGE2. Treatment with anti-IL-10 monoclonal antibodies partially reversed the PGE2-induced suppression of COX-2 mRNA, suggesting that IL-10 may be involved in modulating COX-2 by PGE2. Experiments using an inducer and an inhibitor of cyclic AMP (cAMP) suggest that cAMP is the major intracellular signal that mediates the regulatory effect of PGE2 on COX-2 expression. EMSA revealed that PGE2 inhibited the binding of NF-${\kappa}B$ in the COX-2 promoter via a cAMP dependent pathway. In addition, a subcutaneous injection of PGE2 twice daily for 2 weeks significantly reduced the incidence and severity of CIA as well as the production of IgG antibodies to type II collagen. Conclusion: Our data suggest that overproduced PGE2 in the RA joints may function as an autocrine regulator of its own synthesis by inhibiting COX-2 production and may, in part, play an anti-inflammatory role in the arthritic joints.

• The Journal of Korean Medicine
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• v.34 no.3
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• pp.69-85
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• 2013

Objectives: This study investigated the anti-osteoarthritic effects of Kyejiinsam-tang (hereinafter referred to KIT) on the monosodium iodoacetate (MIA)-induced osteoarthritis rats. Methods: Anti-oxidative effects of KIT were measured by scavenging activities of DPPH, reactive oxygen species (ROS) and nitric oxide (NO). Scavenging activities of anti-oxidation in lipopolysaccharide (LPS)-treated RAW 264.7 cells were also measured for inhibitory effects against the production of inflammatory mediators (tumor necrosis factor-${\alpha}$, interleukin-$1{\beta}$, interleukin-6). Osteoarthritis was induced in rats by injecting MIA in the knee joint. Rats were divided into a total of 4 groups (n=6). The normal group were not treated at all without inducing osteoarthritis whereas the control group were induced for osteoarthritis by MIA and oral medicated physiological saline per day. The positive comparison group was injected with MIA and after 7 days, 2 mg/kg of Indomethacin. The experimental group was injected with MIA and after 7 days was medicated with 34 mg/kg of KIT. Indomethacin and KIT were orally-medicated for each substance a total of 4 weeks, once per day. Weight-bearing on hind legs was measured every week after MIA injection. At the end of the experiment (5 weeks after MIA injection), micro CT (computed tomography)-arthrography and histopathological examinations on the articular structures of knee joint were performed. The effect on inflammatory cytokines and immunological cells in synovial fluid was measured. Volume of cartilage was measured by micro CT-arthrography. Injury to synovial tissue was measured by H & E (hematoxylin and eosin), Safranin-O immunofluorescence. Results: 1. Cytotoxicity against hFCs was insignificant. 2. KIT showed the potent full term for DPPH. 1. NO was significantly reduced by KIT (at 100, $200{\mu}g/m{\ell}$) and ROS was also reduced, but not significantly, by KIT (at $200{\mu}g/m{\ell}$). 2. IL-6 and IL-$1{\beta}$ were significantly reduced by KIT (at 100, $200{\mu}g/m{\ell}$) and TNF-${\alpha}$ was also reduced, but not significantly, by KIT (at $200{\mu}g/m{\ell}$). 1. In hind legs weight-bearing measurement, level of weight increased. 2. Functions of liver and kidney were not affected. 3. IL-$1{\beta}$ was significantly reduced and TNF-${\alpha}$, IL-6 were also reduced but not significantly. 4. PGE2 (prostaglandin E2), LTB4 (leukotriene B4) were significantly reduced in the KIT group. 5. MMP-9 (matrix metalloproteinase-9), TIMP-1 (tissue inhibitor of metalloproteinases-1) and Osteocalcin were significantly reduced in the KIT group. 6. Destruction of cartilage on micro CT arthrography was reduced but had no significant differences. 7. Histopathologically, injury to synovial membrane of the KIT group was decreased and proteoglycan content of KIT group was increased. Conclusions: According to this study, Kyejiinsam-tang has inhibiting effect on the progression of arthritis in MIA-induced osteoarthritis rat. Kyejiinsam-tang has anti-oxidants and anti-inflammation effects, and is related to inhibiting the activity of inflammatory cytokine and injury of volume in cartilage.

• Korean journal of applied entomology
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• v.40 no.1
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• pp.51-58
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• 2001

Entomopathogenic fungus, Paecilomyces japonicus, has been commercially used as medicinal purpose . The silkworm, Bombyx mori, as an optimal host for the fungi, has been selected and used for the production of the fungal fruit bodies. In current method, newly molted fifth instal larvae should be exposed to the adverse stress environment of high temperature (3$0^{\circ}C$), high relative humidity ( 90%), and starvation for 24h for better fungal inoculation to the host insects. In this study, an alternative method using chemical agent, dexamethasone (DEX: an eicosanoid biosynthesis inhibitor), was tried to get the immunodepressive effect on the larvae to elevate the inoculation rate of the fungi to the silkworm without any harsh rearing environment. DEX (100$\mu\textrm{g}$) showed significantly synergistic effect on the hemocyte lethality of the fungus, and was effective to decrease cellular immune responses measured by the number of hemocyte microaggregation and phenoloxidase activity of the fifth instar larvae in response to the fungal injection. A detergent of 0.05% Triton-X was effective to increase the in- oculation rate of the fungi to the larvae and used in all fungal spraying solutions. Without any environ- mental stress treatment, only DEX (100$\mu\textrm{g}$) injection to the fifth instar larvae followed by the fungal spray was effective to get the inoculation rate equivalent to the current fungal spray method requiring harsh rearing environment. These results suggest that the inoculation of P. japonicus can be elevated by the help of DEX and that the silkworms use eicosanoids to elicit cellular immune response against fungal pathogen.

• The Korean Journal of Pain
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• v.13 no.2
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• pp.164-174
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• 2000

Background: After an injury to tissue such as the skin, hyperalgesia develops. Hyperalgesia is characterized by an increase in the magnitude of pain evoked by noxious stimuli. It has been postulated that in the mechanism of hyperalgesia (especially secondary hyperalgesia) and allodynia, a sensitization of central nervous system such as spinal dorsal horn may contribute to development of hyperalgesia. However, the precise mechanism is still unclear. In the present study, we investigated the roles of N-methyl-D-aspartate (NMDA) receptor and nitric oxide (NO) system in the mechanism of hyperalgesia, and their relations with c-fos expression Methods: Inflammation was induced by injection of complete Freund adjuvant (CFA) into unilateral hindpaw of Sprague-Dawley rat. Behavioral studies measuring paw withdrawal responses by von Frey filaments and paw withdrawal latencies by radiant heat stimuli and stainings of nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase and c-fos immunoreactivity were performed. The effects of MK-801, an NMDA receptor blocker and $N^\omega$-nitro-L-arginine (L-NNA), a nitric oxide synthase (NOS) inhibitor were evaluated. Results: 1) Injection of CFA induced mechanical allodynia, mechanical hyperalgesia and thermal hyperalgesia. And it increased the number of NADPH-diaphorase positive neurons and c-fos expression neurons. 2) MK-801 inhibited mechanical hyperalgesia and thermal hyperalgesia induced by CFA and reduced the number of NADPH-diaphorase positive neurons and c-fos expression neurons. 3) L-NNA inhibited the thermal hyperalgesia and reduced the number of NADPH-diaphorase positive neurons, but did not affect the number of c-fos expression neurons. Conclusions: These results suggest that in the mechanism of mechanical hyperalgesia, NMDA receptor but not NO-system is involved and in the case of thermal hyperalgesia both NMDA receptor and NO system are involved. NO system did not affect the expression of c-fos, but c-fos expression and NOS activity were dependent on the activity of NMDA receptor.