• 한국한의학연구원논문집
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• 제12권3호통권18호
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• pp.59-67
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• 2006

Aims: Acupuncture has been used for the treatment of essential hypertension, but the efficacy and the mechanism of acupuncture in prevention of hypertension are still unclear. We tested the hypothesis that electroacupuncture (EA) applied to Baekhoe (GV20) changes NO/NOS system during development of hypertension in spontaneously hypertensive rats (SHR), and thereby causes the delay of development of hypertension in SHR. Methods: The male SHR rats in the developmental stages of hypertension (7-8 weeks) were randomly divided into three groups (control group, GV20 acupuncture group, and tail acupuncture group). And the age matched Wistar Koyto Rats (WKY) were randomly divided into two groups (nagative control, GV20 acupuncture group). EA treatments (10Hz, 1mA, 0.1ms) were carried out for 25 min/day for five consecutive days. The systolic blood pressure (SBP) was determined in conscious rats by the tail-cuff method using automatic BP mornitoring system. We investigated the activations of inducible NO synthase (iNOS) in nuclei of solitary tract (NTS) and rostral ventrolateral medulla (RVLM) of SHR by the western blotting method. Results: The SBP after the termination of EA stimulation applied to the GV20 was stabilized at $169.14{\pm}3.67$ mmHg which is lower value than that of the control group. The SBP of control group was elevated to $178.14{\pm}3.49$ mmHg. In addition, we evaluated NOS activity as well as iNOS protein expression of NTS and RVLM in both of SHR and WKY. The iNOS activity in NTS was significantly higher in SHR than in WKY. Furthermore, the iNOS activity of NTS showed significant decreases in EA groups compare to that of non treated SHR group. Although iNOS expression of RVLM showed non significant changes between SHR and WKY, EA significantly enhanced the iNOS expression in SHR. Our data support the hypothesis that delayed development of hypertension and altered iNOS expression of NTS and RVLM by EA stimulations in SHR rats. Conclusions: The findings demonstrate that acupuncture can change NO/NOS system in NTS and RVLM, and exert beneficial role on development of hypertension.

• The Korean Journal of Physiology and Pharmacology
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• 제11권6호
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• pp.253-257
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• 2007

Among the arthritis symptoms, chronic pain is the most serious, and it can profoundly affect the quality of human life. Unfortunately, the mechanism of development in arthritis and arthritic pain has not yet been precisely elucidated. Accumulating evidence indicates that nitric oxide (NO) plays a pivotal role in nociceptive processing in the spinal cord. However, the modulation mechanism of NO in the peripheral site of arthritis and arthritic pain has not been clarified. Therefore, I determined in the present study which nitric oxide synthase (NOS) was involved in the induction of arthritis and arthritic pain. Monoarthritis was induced by intra-articular injection of carrageenan (2%, $50{\mu}l$) into rats, and resulted in the reduction of weight load on the injected leg, increase of knee joint diameter and inflammatory response. Pre-treatment of rats with L-N6-(1-iminoethyl)-lysine (L-NIL, $500{\mu}g$, in $50{\mu}l$), an inhibitor of inducible NOS (iNOS), partially prevented the induction of pain-related behavior and partially reduced inflammatory response in the synovial membrane in the knee joint. These results suggest that iNOS in the knee joint may play an important role in the induction of pain-related behavior and inflammation, and that NO produced by iNOS may be associated with nociceptive signaling in the peripheral site.

• 한국방사선학회논문지
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• 제13권1호
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• pp.133-140
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• 2019

중성지방(Triglyceride, TG)는 죽상동맥경화증과 같은 혈관의 만성 염증성 병변을 유발하는 인자 중 하나이다. 종양괴사인자-알파 ($TNF-{\alpha}$), 인터루킨-1 베터 ($IL-1{\beta}$)와 같은 염증성 사이토카인은 염증 질환의 주요 요인으로 염증 부위에 T 림프구, 단핵구등의 면역 세포의 침윤을 유도하거나 세포 및 조직 괴사를 일으킴으로써 질병을 더욱 악화시킨다. 본 연구에서는 혈관 염증에 관여하는 Jurkat T 림프구와 U937 단핵구에 TG를 처리하였을 때 $TNF-{\alpha}$와 $IL-1{\beta}$의 발현에 미치는 영향을 조사하고자 했다. Jurkat T 세포에서 TG에 의해 $TNF-{\alpha}$의 mRNA 발현이 증가하였고, U937 단핵구에서는 TG에 의해 $TNF-{\alpha}$와 $IL-1{\beta}$ 모두 mRNA 발현이 증가하였다. 또한 유도성 산화질소합성효소(inducible nitric oxide synthase, iNOS)가 TG에 의한 $TNF-{\alpha}$와 $IL-1{\beta}$의 발현 증가에 관여하는지 확인하기 위해 iNOS 억제제인 W1400을 세포에 전처리하여 iNOS의 활성을 차단하였다. 그 결과, W1400을 전처리한 세포에서는 TG에 의한 $TNF-{\alpha}$ 및 $IL-1{\beta}$ mRNA 양이 대조군과 유사하게 낮은 수준으로 관찰되었다. 이는 혈관 내 TG의 증가가 T 림프구와 단핵구를 자극하여 iNOS 신호를 거쳐 염증성 사이토카인을 분비시키고 혈관염증질환을 발생하는데 관여하는 것을 확인시켜주었다. 결론적으로, 중성지방이 염증성 병변을 악화시키는데 있어 iNOS의 활성이 사이토카인 분비 등에 작용하며 병변을 더욱 악화시키는데 기여할 수 있다. 반면, iNOS 발현을 조절하여 고지혈증 환자의 치료에 유효한 표적 물질로 이용될 가능성이 있다고 사료된다.

• 동의생리병리학회지
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• 제26권3호
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• pp.293-300
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• 2012

Inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) are important inflammatory mediators implicated in pathogenesis of inflammation and certain types of human cancers. The present study was designed to determine whether Red Ginseng (RG) could modulate $I{\kappa}B$-kinase, iNOS and COX-2 gene expression and immune responses in RAW 264.7 macrophages stimulated with lipopolysaccharide (LPS). RG extract suppressed the expression of LPS-induced $I{\kappa}B$, iNOS, COX-2, and immune responses in a dose-dependent manner. It also showed an anti-inflammatory effect by inhibiting NF-${\kappa}B$ immune response induced by LPS treatment. Inhibitory effect of RG on LPS-induced inflammation was mediated by suppressed phosphorylation of ERK, JNK and p38 through the regulation of the mitogen-activated protein kinase (MAPK) pathway leading to a decreased production of NO, iNOS, COX-2 and NF-${\kappa}B$. The results implied the role of RG as an inflammation regulator and its possible application for curing inflammatory diseases.

• Tuberculosis and Respiratory Diseases
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• 제42권4호
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• pp.447-454
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• 1995

Cytokine release from alveolar macrophages and subsequent interaction of these cytokines with the bronchial epithelium can induce epithelial cells to release inflammatory mediators. Nitric oxide(NO), a highly reactive gas formed from arginine by nitric oxide synthase(NOS), is known to be involved in inflammation and edema formation, and the inducible form of NOS(iNOS) can be increased by cytokines. In this context, we hypothesized that lung epithelial cells could be stimulated by cytokines released by alveolar macrophages to express iNOS. To test this hypothesis, the murine lung epithelial cell line, LA-4, or the human lung epithelial cell line, A549, were stimulated with culture supernatant fluids from alveolar macrophages. NO production was assessed by evaluating the culture supernatant fluids for nitrite and nitrate, the stable end products of NO. Both murine and human cell culture supernatant fluids demonstrated an increase in nitrite and nitrate which were time- and dose-dependent and attenuated by $TNF{\alpha}$ and IL-$1{\beta}$ antibodies(p<0.05, all comparisons). Consistent with these observations, cytomix a combination of $TNF{\alpha}$, IL-$1{\beta}$, and $\gamma$-interferon, stimulated the lung epithelial cell lines as well as primary cultures of human bronchial epithelial cells to increase their NO production as evidenced by an increase in nitrite and nitrate in their culture supernatant fluids, an increase in the iNOS staining by immunocytochemistry, and an increase in iNOS mRNA by Northern blottin(p<0.05, all comparisons). The cytokine effects on iNOS were all attenuated by dexamethasone. To determine if these in vitro observations are reflected in vivo, exhaled NO was measured and found to be increased in asthmatics not receiving corticosteroids. These data demonstrate that alveolar macrophage derived cytokines increase iNOS expression in lung epithelial cells and that these in vitro observations are mirrored by increased exhaled NO levels in asthmatics. Increased NO in the lung may contribute to edema formation and airway narrowing.

• Korean Journal of Acupuncture
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• 제30권4호
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• pp.264-271
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• 2013

Objectives : To observe the changes in the expression of neurotransmitters NO and enzymes that create NO, such as nNOS, iNOS and eNOS, upon the needle insertion on river point, one of the five transport points of three yang meridians on the forefoot. Methods : Based on rats, needle was inserted on both sides of LI5, SI5 and TE6, which are river points of three yang meridians on the forefoot, and were retained for five minutes. After the retention, blood was drawn via cardiac puncture and tissues from each point around meridian vessels were extracted to be examined on the changes of the expression of NO, as well as of nNOS, iNOS and eNOS. Results : In terms of the effect on NO creation in tissues, none of the experimental groups showed any significant change compared to the Normal group. In terms of the effect on expression of nNOS within tissues, LI5 and SI5 showed significant increase based on the results of immunohistochemistry. In iNOS within tissues, LI5 and SI5 showed significant increase based on the results of immunohistochemistry. In eNOS within tissues, SI5 showed significant increase based on the results of immunohistochemistry. Conclusions : The effect on the function of NO, nNOS, iNOS and eNOS of needle insertion on the river points of three yang meridians on the forefoot could be observed, and based on this study, it is considered that the effect of needle stimulation on the changes of nervous system could be found out through additional research.

• Korean Journal of Acupuncture
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• 제30권1호
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• pp.37-46
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• 2013

Objectives : The Meridians and acupuncture points are the fundamental theories for acupuncture therapy. They have been associated with nervous system, but It is not well defined. We investigated that the effects of acupuncture at the river points(LU8, HT4, PC5, SP5, KI7, LR4) on the changes in the expression of nNOS, iNOS, eNOS, and NE in rats. Methods : The Male Sprague-Dawley rats were divided into 6 groups each non-acupuncture and acupuncture group. We inserted needle and retained for 5 minutes on both left and right sides of LU8, HT4, PC5, SP5, KI7, LR4 which were the river points of five transport points for 6 yin meridian vessels. After that, blood was drawn via cardiac puncture, and tissues for each point near meridian vessels were extracted to examine the changes in the changes of nNOS, eNOS, iNOS and NE. Results : The LU8 and HT4 group showed a significant decrease on nNOS. In terms of eNOS and iNOS, the LU8 group decreased significantly while the KI7 group increased significantly. However, the experimental groups didn't show any significant changes on the plasma and tissue norepinephrine without plama NE in SP5 group. Conclusions : The effect on the nNOS, iNOS, eNOS of acupuncture at LU8 and KI7 could be observed, and it is considered that the effect of acupuncture related with on nervous system could be studied by additional researches based on this one.

• Korean Journal of Acupuncture
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• 제30권2호
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• pp.97-103
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• 2013

Objectives : To observe the changes in the expression of nNOS, iNOS, eNOS and NO by the needle insertion on river points, one of the five transport points of three yang meridians of the foot. Methods : Based on rats, needle was inserted on both left and right sides of ST41, BL60 and GB38 and retained for five minutes. After the retention, blood was drawn via cardiac puncture and tissues from each point around meridian vessels were extracted to observe the changes in the expression of nNOS, iNOS, eNOS and NO. Results : In terms of the effect on expression of nNOS within tissues, ST41 showed significant decrease based on the results of immunohistochemistry. In terms of the effect on expression of iNOS within tissues, none of the experimental groups showed any significant change compared to the Normal group. Regarding expression of eNOS within tissues, GB38 showed significant increase based on the results of immunohistochemistry. In terms of the effect on NO creation in tissues, none of the experimental groups showed any significant change compared to the Normal group. Conclusions : The effect of needle insertion on the river points of three yang meridians of the foot on the function of nNOS, iNOS, eNOS and NO could be observed, and based on this study, it is considered that the effect of needle stimulation on the changes of nervous system could be found out through additional research.

• 한국과학교육학회지
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• 제28권7호
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• pp.749-758
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• 2008

Even though the importance of the nature of science (NOS) and scientific inquiry in science learning have been emphasized by many science educators and science curriculums, the link between the NOS and scientific inquiry has not been discussed sufficiently. In this article, I discussed that various aspects of NOS are already embedded in defining and characterizing the authentic scientific inquiry and that we need to have special concern about how the NOS should be treated and interpreted when introducing it into scientific inquiry. And I summarized two approaches to teach the NOS and scientific inquiry; teaching the NOS through scientific inquiry and teaching scientific inquiry through the NOS. Finally, some next studies based on this article are introduced.

• Natural Product Sciences
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• 제5권3호
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• pp.113-120
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• 1999

Nitric oxide (NO) is a free radical synthesized from L-arginine by nitric oxide synthase (NOS). It is believed that NO is an important mediator in numerous physiological and inflammatory responses. Particularly, a large amount of NO released from the inducible nitric oxide synthase (iNOS) is mostly associated with inflammatory processes. Overproduction of NO in these processes including sepsis and autoimmune diseases can have deleterious consequences and pathophysiologic relevance. Therefore, for the discovery of new inhibitory agents against iNOS activity, we have evaluated about 100 kinds of natural products after partition into three layers (n-hexane, ethyl acetate and aqueous) from 100% methanol extracts to study inhibitory effects on iNOS activity induced by lipopolysaccharide (LPS) in RAW264.7 cells culture system. As a positive control, curcumin, which is known as an anti-tumor promoter, anti-inflammatory agent as an iNOS inhibitor, was used and showed the dose-dependent inhibitory effect $(IC_{50},\;2.5\;{\mu}g/ml)$. Among tested fractions, the n-hexane fraction of Cimicifuga heracleifolia $(IC_{50}:\;9.65\;{\mu}g/ml)$, Forsythiae fructus $(IC_{50}:\;6.36\;{\mu}g/ml)$, Saposhnikovia divaricata $(IC_{50}:\;5.92\;{\mu}g/ml)$, and the ethyl acetate fraction of Chrysanthemum sibiricum $(IC_{50}:\;2.56\;{\mu}g/ml)$, Gastrodia elata $(IC_{50}:\;3.46\;{\mu}g/ml)$, and the aqueous fraction of Dianthus chinensis $(IC_{50}:\;6.73\;{\mu}g/ml)$, Euonymus alatus $(IC_{50}:\;6.78\;{\mu}g/ml)$, Mechania urticifoloria $(IC_{50}:\;8.01\;{\mu}g/ml)$ showed strong inhibitory activity against LPS-stimulated iNOS. Especially, the ethyl acetate fraction of Chrysanthemum sibiricum $(IC_{50}:\;2.56\;{\mu}g/ml)$, which exhibited the strongest inhibition against iNOS, was fractionated with silica-gel column chromatography. These subfractions exhibited dose-dependent inhibition against iNOS activity in the range of $2.59-5.6\;{\mu}g/ml$ except for fraction No. 3, 4, 5, 6, 8, 9, and 16. Our study shows that Chrysanthemum sibiricum has the strongest inhibitory effect against iNOS activity and has similar effect to curcumin. Therefore, further studies for the identification of active principles from Chrysanthemum sibiricum and investigation for the mechanism of the inhibition of iNOS by active principles will be performed.