• Toxicological Research
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• 제12권2호
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• pp.195-201
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• 1996

Endotoxic shock causes death in humans and animals via extreme hypoperfusion of peripheral organs. A massive production of nitric oxide (NO) both from the endothelical cells and smooth muscle cells has been proposed as a possible mechanism in this process. Since NO attenuated the contractility to vasoconstricting agents such as norepinephrine (NE) by directly acting on the smooth muscle cells, this mechanism was considered mainly as a postsynaptic mechanism. In this research it was investigated whether NO, thus released, also participates in the presynaptic events for the regulation of vascular tone in endotoxic shock. The role of NO was studied by adding NO donors or NO synthase inhibitor $N^\omega $methyl-L-arginine (NMA) in stimulated sympathetic nerves of the mesenteric vascular bed and the Langendorff heart of rats. Sodium nitroprusside (SNP), an NO donor, reduced the pressor responses of isolated mesenteric artery either to electrical stimulation or exogenously administered phenylephrine (PE). In this mesentery, although neither agent influenced NE release, in the presence of the adrenergic $\alpha_2$-receptor antagonist yohimbine, elecrical stimulation-evoked NE release was augumented by SNP. In the heart SNP facilitated the NE release induced by electrical stimulation, while NMA had no effect. From these results it is proposed that there exists a local reflex phenomenon in the junction between the sympathetic nerve terminals and the smooth muscle of resistance blood vessels; by which sympathetic responses are reduced by NO at the postjunctional level while NO facilitates NE release contributing to augumentation of sympathetic tone. All these facts suggest that NO produced during endotoxic shock has dual effects: whereas NO blunts the vasoconstrictive activity of NE at the postsynaptic level, NO presynaptically facilitates the release of NE from sympathetic nerve terminals.

• Journal of Applied Biological Chemistry
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• 제62권3호
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• pp.305-313
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• 2019

남성의 클라이맥스 증후군, 남성갱년기, 또는 테스토스테론 결핍 증후군은 고령화시대 남성노인들의 건강에 새로운 문제 중 하나이다. 이 현상은 나이가 들수록 남성에게서 나타나는 자연현상으로 혈중 테스토스테론 수치의 감소와 신체적 및 정신적 활동의 현저한 감소를 특징으로 한다. 이 연구의 목적은 해면체내 일산화질소(NO)와 혈액 내 남성호르몬의 수준을 비교하여 포공영(Taraxacum coreanum) 열수 추출물의 효과를 조사하였다. 포공영 추출물은 생체외 및 생체내에서 NO 생산량을 용량 의존적으로 증가시켰다. 포고영 추출물을 4 주간 섭취 한 나이든 쥐(22주)에서 다이하이드로 테스토스테론과 17-하이드록시 스테로이드 탈수소효소의 수준과 신경 인산화 질소 합성효소와 cGMP의 양은 유의하게 증가했다. 그러나 프로스타글란딘$E_2$, 테스토스테론 및 성 호르몬 결합 글로불린 수치는 모든 군에서 차이가 없었다. 또한, 총 정자 수 및 운동성 정자 수 또한 유의한 차이가 없었다. 전반적으로, 이러한 결과는 NO, cGMP 및 유리 테스토스테론을 향상시키기 위한 안전하고 효과적인 천연물질로서 Taraxacum coreanum 추출물의 가능성을 시사한다.

• The Korean Journal of Physiology and Pharmacology
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• 제25권5호
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• pp.449-457
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• 2021

The sleep-wake cycle is regulated by the alternating activity of sleep- and wake-promoting neurons. The dorsal raphe nucleus (DRN) secretes 5-hydroxytryptamine (5-HT, serotonin), promoting wakefulness. Melatonin secreted from the pineal gland also promotes wakefulness in rats. Our laboratory recently demonstrated that daily changes in nitric oxide (NO) production regulates a signaling pathway involving with-no-lysine kinase (WNK), Ste20-related proline alanine rich kinase (SPAK)/oxidative stress response kinase 1 (OSR1), and cation-chloride co-transporters (CCC) in rat DRN serotonergic neurons. This study was designed to investigate the effect of melatonin on NO-regulated WNK-SPAK/OSR1-CCC signaling in wake-inducing DRN neurons to elucidate the mechanism underlying melatonin's wake-promoting actions in rats. Ex vivo treatment of DRN slices with melatonin suppressed neuronal nitric oxide synthase (nNOS) expression and increased WNK4 expression without altering WNK1, 2, or 3. Melatonin increased phosphorylation of OSR1 and the expression of sodium-potassium-chloride co-transporter 1 (NKCC1), while potassium-chloride co-transporter 2 (KCC2) remained unchanged. Melatonin increased the expression of tryptophan hydroxylase 2 (TPH2, serotonin-synthesizing enzyme). The present study suggests that melatonin may promote its wakefulness by modulating NO-regulated WNK-SPAK/OSR1-KNCC1 signaling in rat DRN serotonergic neurons.

• 대한화장품학회:학술대회논문집
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• 대한화장품학회 2003년도 IFSCC Conference Proceeding Book I
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• pp.601-610
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• 2003

Biotin is a water-soluble vitamin used as a skin conditioning agent and promotes the formation of intercellular lipid layers through increased lipid synthesis, which improves the skin's natural barrier function. The anti-inflammatory effects of biotin have been investigated using in vitro assay models, such as MTT assay, measurements of concentrations of nitric oxide(NO), prostaglandin E2(PGE$_2$), and inhibition rate of 5-lipoxygenase(5-LOX). In comparison with biotin, other plant extracts were tested at the same time which were kudzu vine extract, sage extract, paeonia extract, and dipotassium glycyrrhetinate. Nitric oxide is a signal molecule with functions such as neurotransmission, local vascular relaxation, and anti-inflammation in many physiological and pathological processes. NO can cause apoptosis and necrosis of target cells such as keratinocytes and is generated from L-arginine by nitric oxide synthase (NOS). Prostanoids, including prostaglandins and thromboxanes, are generated by the phospholipase $A_2$/cyclooxygenase(COX) pathway, and leukotrienes are generated by the 5-lipoxygenase pathway from arachidonic acid. Prostaglandin E2 recently have been shown to be beneficial in the resolution of tissue injury and inflammation, also has been implicated as an immunosuppressive agent and plasma levels of PGE$_2$ are elevated in patients sustaining thermal injury. Lipoxygenase metabolites from arachidonic acid have been implicated in inflammation, anti-inflammatory activity of the raw materials was evaluated in vitro by the offered inhibition of lipoxygenase.

• 대한한방내과학회지
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• 제26권3호
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• pp.605-614
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• 2005

Objectives : Ojawhan was formulated to contain various natural products known to cure erectile dysfunction. This study was aimed to investigate the effects of Ojawhan on the nitric oxide synthase(NOS) activity, nitrite level, antioxidation and erectile responses in rat's corpus cavernosum penis. Methods : Ojawhan was washed, dried in the shade and crushed. The crushed Ojawhan ,was extracted 3 times, each time with 3 volumes of methyl alcohol at $60^{\circ}C$ for 24 h. The extract was filtered and evaporated under a reduced pressure using a rotary evaporator to yield 62g. Ojawhan extract oral-administered 100 mg per 1 kg of body weight for 30 days. First, samples were treated with Ojawhan, then ethanol-treated rats and L-N-Nitroarginine methyl ester(L-NAME) treated rats were put with the samples. Result : The level of urethral lipid peroxide in the ethanol-Ojawhan double administered rats was decreased as low as in the normal group, while the one in the ethanol-treated group was increased. The urethral NOS activity, the level of urethral nitrite, the level of testosterone and the erectile response to cavernous nerve stimulation in the ethanol-Ojawhan double administered rats were increased as high as in the normal group while the one in the ethanol-treated group was decreased. The electile response to cavernous nerve stimulation and the level of nitrite in L-NAME ($10^{-4}$)-treated rats was restored by the administration of Ojawhan as high as in the normal group. Conclusions : Ojawhan was effective in restoring the ethanol-induced or L-NAME-induced erectile dysfunction in rats.

• Food Science and Biotechnology
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• 제16권5호
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• pp.728-733
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• 2007

Bamboo grass, Sasa quelpaertensis, is a native plant to Jeju Island, Korea. The leaves of Sasa plants are widely used in traditional Korean medicine to treat inflammation-related diseases. We investigated the effect of hot water extract from Sasa quelpaertensis leaves (HWE-SQ) on nitric oxide (NO) production and nuclear $factor-{\kappa}B\;(NF-{\kappa}B)$ activation in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. HWE-SQ inhibited LPS-induced NO production and inducible NO synthase (iNOS) protein expression in a dose-dependent manner. Reporter gene assays indicated that HWE-SQ decreases LPS-induced $NF-{\kappa}B$ transcriptional activation. However, HWE-SQ did not affect the phosphorylation and degradation of inhibitory ${\kappa}B{\alpha}\;(1{\kappa}B{\alpha})$. HWE-SQ also directly inhibited iNOS enzyme activity in a dose-dependent manner. These results suggest that HWE-SQ suppresses NO synthesis in macrophages by attenuating $NF-{\kappa}B-mediated$ iNOS protein expression and inhibiting iNOS enzymatic activity, thereby implicating a mechanism by which HWE-SQ is able to ameliorate inflammation-related diseases by limiting excessive or prolonged NO production in pathological events.

• 동의생리병리학회지
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• 제23권2호
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• pp.416-425
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• 2009

Angiogenesis is important for promoting cardiovascular disease, wound healing, and tissue regeneration. We here investigated the pharmacological effects of Korea red ginseng water extract (KRGE) on angiogenesis and its underlying signal mechanism. This study showed that KRGE increased in vitro proliferation, migration, and tube formation of human umbilical endothelial cells, as well as stimulated in vivo angiogenesis. KRGE-induced angiogenesis was accompanied by phosphorylation of ERK1/2, Akt, and endothelial nitric oxide synthase (eNOS) as well as an increase in NO production. Inhibition of PI3K activity by wortmannin completely inhibited KRGE-induced angiogenesis and phosphorylation of Akt, ERK1/2, and eNOS, indicating that PI3K/Akt activation is an upstream event of KRGE-mediated angiogenic pathway. The MEK inhibitor PD98059 completely blocked KRGE-induced angiogenesis and ERK phosphorylation without affecting Akt and eNOS activation. However, the eNOS inhibitor NMA effectively inhibited tube formation, but partially blocked proliferation and migration as well as ERK phosphorylation without altering Akt and eNOS activation, revealing that eNOS/NO pathway is in part involved in ERK1/2 activation. This study first demonstrated the critical involvement of both ERK1/2 and eNOS activation in KRGE-induced angiogenesis, which lie on downstream of PI3K/Akt. Thus, these results indicate that KRGE requires activation of both the PI3K/Akt-dependent ERK1/2 and eNOS signal pathways and their cross-talk for its full angiogenic activity.

• 동의생리병리학회지
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• 제25권2호
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• pp.234-241
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• 2011

Mantidis Vagina Ovorum was formulated to contain various natural products known to cure erectile dysfunction. This study was aimed to investigate the effects of Mantidis Vagina Ovorum on the nitric oxide synthase (NOS) activity, nitrite level, antioxidation and erectile responses in rat's corpus cavernosum penis. The crushed Mantidis Vagina Ovorum was extracted 3 times, each time with 3 volumes of methyl alcohol at $60^{\circ}C$ for 24 h. The extract was filtered and evaporated under a reduced pressure using a rotary evaporator to yield 16.6 g. Mantidis Vagina Ovorum extract oral-administered 75 mg per 1 kg of body weight for 30 days. First, samples were treated with Mantidis Vagina Ovorum, and then cimetidine-treated rats and L-N-Nitroarginine methyl ester (L-NAME) treated rats were put with the samples. The level of urethral lipid peroxide in the cimetidine-Mantidis Vagina Ovorum double administered rats was decreased as low as in the normal group, while the one in the cimetidine-treated group was increased. The urethral NOS activity, the level of urethral nitrite, the level of testosterone and the electile response to cavernous nerve stimulation in the cimetidine-Mantidis Vagina Ovorum double administered rats were increased as high as in the normal group while the one in the cimetidine-treated group was decreased. The electile response to cavernous nerve stimulation and the level of nitrite in L-NAME ($10^{-4}$)-treated rats was restored by the administration of Mantidis Vagina Ovorum as high as in the normal group. Mantidis Vagina Ovorum was effective in restoring the cimetidine-induced or L-NAME-induced erectile dysfunction in rats.

• 한국축산식품학회지
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• 제38권6호
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• pp.1226-1236
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• 2018

Ovotransferrin (OTF) is a well-known protein of the transferrin family with strong iron chelating activity, resulting in its antimicrobial activity. Furthermore, OTF is known to have antioxidant, anticancer, and antihypertensive activities. However, there have been few studies about the immune-enhancing activity of OTF. In current study, we investigated the immune-enhancing activity of OTF using the murine macrophage cells in vitro. The effect of OTF on production of pro-inflammatory mediators and cytokines were determined using Griess assay and quantitative real-time PCR. Using Neutral Red uptake assay, we confirmed the effect of OTF on phagocytic activity of macrophages. Ovotransferrin significantly increased the production of nitric oxide (NO) and secretion of inducible nitric oxide synthase (iNOS) mRNA with no cytotoxic activity. Ovotransferrin (2 mg/mL) stimulated NO production up to $31.9{\pm}3.5{\mu}M$. Ovotransferrin significantly increased the mRNA expression levels of pro-inflammatory cytokines which are tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), Interleukin-$1{\beta}$ (IL-$1{\beta}$), and IL-6: OTF (2 mg/mL) treatment increased the secretion of mRNA for TNF-${\alpha}$, IL-$1{\beta}$, and IL-6 by 22.20-, 37.91-, and 6.17-fold of the negative control, respectively. The phagocytic activity of macrophages was also increased by OTF treatment significantly compared with negative control. Also, OTF treatment increased phosphorylation level of MAPK signaling pathways. These results indicated that OTF has immune-enhancing activity by activating RAW 264.7 macrophages via MAPK pathways.

• Journal of Korean Neurosurgical Society
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• 제38권4호
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• pp.287-292
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• 2005

Objective : Kainic acid[KA] enhances the expression of nitric oxide synthase, increases nitric oxide[NO], and thus evokes epileptic convulsion, which results in neuronal damage in the rat brain. NO may stimulate cyclooxygenase type-2 [COX-2] activity, thus producing seizure and neuronal injury, but it has also been reported that KA-induced seizure and neurodegeneration are aggravated on decreasing the COX-2 level. This study was undertaken to investigate whether the suppression of NO using the NOS inhibitor, N-nitro-L-arginine methyl ester[L-NAME], suppresses or enhances the activity of COX-2. Methods : Silver impregnation and COX-2 immunohistochemical staining were used to localize related pathophysiological processes in the rat forebrain following KA-induced epileptic convulsion and L-NAME pretreatment. Post-injection survival of the rat was 1, 2, 3days and 2months, respectively. Results : After the systemic administration of KA in rats, neurodegeneration increased with time in the cornu ammonis [CA] 3, CA 1 and amygdala, as confirmed by silver impregnation. On pretreating L-NAME, KA-induced neuronal degeneration decreased. COX-2 enzyme activities increased after KA injection in the dentate gyrus, CA 3, CA 1, amygdala and pyriform cortex, as determined by COX-2 staining. L-NAME pretreatment prior to KA-injection, caused COX-2 activities to increase compared with KA- injection only group by 1day and 2days survival time point. Conclusion : These results suggest that L-NAME has a neuroprotective effect on KA-induced neuronal damage, especially during the early stage of neurodegeneration.