Heme oxygenase-1 (HO-1)/carbon monoxide (CO) axis suppresses RANKL-induced osteoclastic differentiation by inhibiting redox-sensitive NF-κB activation

( Sun-uk Bak ),( Suji Kim ),( Hae-jun Hwang ),( Jung-a Yun ),( Wan-sung Kim ),( Moo-ho Won ),( Ji-yoon Kim ),( Kwon-soo Ha ),( Young-guen Kwon ),( Young-myeong Kim ) 생화학분자생물학회 2017 BMB Reports Vol.50 No.2

Heme oxygenase (HO-1) catalyzes heme to carbon monoxide (CO), biliverdin/bilirubin, and iron and is known to prevent the pathogenesis of several human diseases. We assessed the beneficial effect of heme degradation products on osteoclastogenesis induced by receptor activator of NF-κB ligand (RANKL). Treatment of RAW264.7 cells with CORM-2 (a CO donor) and bilirubin, but not with iron, decreased RANKLinduced osteoclastogenesis, with CORM-2 having a more potent anti-osteogenic effect. CORM-2 also inhibited RANKLinduced osteoclastogenesis and osteoclastic resorption activity in marrow-derived macrophages. Treatment with hemin, a HO-1 inducer, strongly inhibited RANKL-induced osteoclastogenesis in wild-type macrophages, but was ineffective in HO-1^+/-cells. CORM-2 reduced RANKL-induced NFATc1 expression by inhibiting IKK-dependent NF-κB activation and reactive oxygen species production. These results suggest that CO potently inhibits RANKL-induced osteoclastogenesis by inhibiting redox-sensitive NF-κB-mediated NFATc1 expression. Our findings indicate that HO-1/CO can act as an antiresorption agent and reduce bone loss by blocking osteoclast differentiation. [BMB Reports 2017; 50(2): 103-108]

Antioxidant and hepatoprotective effects of Korean ginseng extract GS-KG9 in a D-galactosamine-induced liver damage animal model

Yun Ho Jo,Hwan Lee,Myeong Hwan Oh,Gyeong Hee Lee,You Jin Lee,Ji Sun Lee,Min Jung Kim,Won Yong Kim,Jin Seong Kim,Dae Seok Yoo,Sang Won Cho,Seon Woo Cha,Mi Kyung Pyo 한국영양학회 2020 Nutrition Research and Practice Vol.14 No.4

BACKGROUND/OBJECTIVES: This study was designed to investigate the improvement effect of white ginseng extract (GS-KG9) on D-galactosamine (Ga1N)-induced oxidative stress and liver injury. SUBJECTS/METHODS: Sixty Sprague-Dawley rats were divided into 6 groups. Rats were orally administrated with GS-KG9 (300, 500, or 700 mg/kg) or silymarin (25 mg/kg) for 2 weeks. The rats of the GS-KG9- and silymarin-treated groups and a control group were then intraperitoneally injected Ga1N at a concentration of 650 mg/kg for 4 days. To investigate the protective effect of GS-KG9 against GalN-induced liver injury, blood liver function indicators, anti-oxidative stress indicators, and histopathological features were analyzed. RESULTS: Serum biochemical analysis indicated that GS-KG9 ameliorated the elevation of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) in GalN-treated rats. The hepatoprotective effects of GS-KG9 involved enhancing components of the hepatic antioxidant defense system, including glutathione, glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT). In addition, GS-KG9 treatment inhibited reactive oxygen species (ROS) production induced by GalN treatment in hepatocytes and significantly increased the expression levels of nuclear factor erythroid-2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) proteins, which are antioxidant proteins. In particular, by histological analyses bases on hematoxylin and eosin, Masson"s trichrome, α-smooth muscle actin, and transforming growth factor-β1 staining, we determined that the administration of 500 mg/kg GS-KG9 inhibited hepatic inflammation and fibrosis due to the excessive accumulation of collagen. CONCLUSIONS: These findings demonstrate that GS-KG9 improves GalN-induced liver inflammation, necrosis, and fibrosis by attenuating oxidative stress. Therefore, GS-KG9 may be considered a useful candidate in the development of a natural preventive agent against liver injury.

크론병에 대한 CoPPLX의 방어효과에 대한 연구

이호학,김유림,문창기,이재일,양병윤,김종수,이정민,정재혁,안석진,박상준,김윤권,김소연,김영중,조민구,최영자,장성조 圓光大學校 醫科學硏究所 2005 圓光醫科學 Vol.20 No.1

U-City 적용 기술의 경제성 분석 방법에 관한 연구

김호기(Kim, Ho-Kee),김지현(Kim, Ji-Hyun),곽윤철(Kwak, Yun-Chul),정창무(Jung, Chang-Mu) 대한국토·도시계획학회 2012 國土計劃 Vol.47 No.2

This research is follow-up study of Kim Ji-Hyun?Kim Ho-Kee?Jung Chang-Mu(2010) and Kim Ji-Hyun?Kim Ho-Kee(2010). The fields of technology for applying to U-City are extensive and each type of technology within the sector is diverse. Such being the case, the purpose of this research is to suggest a process(or method) for analyzing economic efficiency of U-City technologies. The process is composed of few works that technology classification, deduction of assessment items, making questionnaire, survey and analysis. By using conjoint analysis, we can calculate few results like values of each technology, marginal rate of substitution between assessment items. Those values are very useful to analysis economic efficiency of U-City technologies. This research has its meaning as attempt to suggest methodology for creating a standard of judgement that can be used to choose more efficient technologies.

Vascular Protective Role of Samul-Tang in HUVECs: Involvement of Nrf2/HO-1 and NO

Choi, Eun Sik,Lee, Yun Jung,Seo, Chang Seob,Yoon, Jung Joo,Han, Byung Hyuk,Park, Min Cheol,Kang, Dae Gill,Lee, Ho Sub Hindawi Publishing Corporation 2016 Evidence-based Complementary and Alternative Medic Vol.2016 No.-

<P>Samul-Tang (Si-Wu-Tang, SMT), composed of four medicinal herbs, is a well-known herbal formula treating hematological disorder or gynecologic disease. However, vascular protective effects of SMT and its molecular mechanisms on the vascular endothelium, known as the central spot of vascular inflammatory process, are not reported. The aim of this study was to investigate vascular protective effects of SMT water extract in human umbilical vein endothelial cells (HUVECs). Water extract of SMT was prepared and identified by HPLC-PDA analysis. Expression of cell adhesion molecules (CAMs) and heme oxygenase-1 (HO-1) and translocation of nuclear factor-kappa B (NF-<I>κ</I>B) and nuclear factor-erythroid 2-related factor 2 (Nrf2) were determined by western blot. Nuclear localization of NF-<I>κ</I>B and Nrf2 was visualized by immunofluorescence and DNA binding activity of NF-<I>κ</I>B was measured. ROS production, HL-60 monocyte adhesion, and intracellular nitric oxide (NO) were also measured using a fluorescent indicator. SMT suppressed NF-<I>κ</I>B translocation and activation as well as expression of CAMs, monocyte adhesion, and ROS production induced by TNF-<I>α</I> in HUVECs. SMT treated HUVECs showed upregulation of HO-1 and NO which are responsible for vascular protective action. Our study suggests that SMT, a traditionally used herbal formula, protects the vascular endothelium from inflammation and might be used as a promising vascular protective drug.</P>

<i>Prunella vulgaris</i> Suppresses HG-Induced Vascular Inflammation via Nrf2/HO-1/eNOS Activation

Hwang, Sun Mi,Lee, Yun Jung,Yoon, Jung Joo,Lee, So Min,Kim, Jin Sook,Kang, Dae Gill,Lee, Ho Sub Molecular Diversity Preservation International (MD 2012 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol.13 No.1

<P>Vascular inflammation is an important factor which can promote diabetic complications. In this study, the inhibitory effects of aqueous extract from <I>Prunella vulgaris</I> (APV) on high glucose (HG)-induced expression of cell adhesion molecules in human umbilical vein endothelial cells (HUVEC) are reported. APV decreased HG-induced expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin. APV also dose-dependently inhibited HG-induced adhesion of HL-60 monocytic cells. APV suppressed p65 NF-κB activation in HG-treated cells. APV significantly inhibited the formation of intracellular reactive oxygen species (ROS). HG-stimulated HUVEC secreted gelatinases, however, APV inhibited it. APV induced Akt phosphorylation as well as activation of heme oxygenase-1 (HO-1), eNOS, and nuclear factor E2-related factor 2 (Nrf2), which may protect vascular inflammation caused by HG. In conclusion, APV exerts anti-inflammatory effect via inhibition of ROS/NF-κB pathway by inducing HO-1 and eNOS expression mediated by Nrf2, thereby suggesting that <I>Prunella vulgaris</I> may be a possible therapeutic approach to the inhibition of diabetic vascular diseases.</P>

폐주불사를 혼입한 콘크리트의 내구성에 관한 연구

김태경,박정호,이정호,이주형,박제선,김연경,윤경구 강원대학교 석재복합신소재제품연구센터 1998 석재연 논문집 Vol.3 No.-

콘크리트 구조물은 자연적인 혹은 인위적인 온도의 상승, 강하로 인하여 동결-융해 작용을 받게 되어 구조물의 성능저하를 야기시킨다. 현대에 들어서면서 콘크리트의 내구특성을 파악하기 위한 연구적 요구가 증가되고 있다. 따라서 폐주물사 콘크리트를 실제 구조물에 적용하기 위해서는 내구특성에 대한 연구가 반드시 이루어져야 한다. 폐주물사를 혼입한 콘크리트의 내구특성을 파악하기 위한 동결-융해 실험은 폐주물사의 잔골재 치환율, 물-시멘트비, AE제 사용 여부를 주요 변수로 하여 실시하였다. 원형공시체를 제작하여, 동결-융해 시험기에 넣어 -18∼4℃로 급속 동결-융해를 진행시키면서 매 23싸이클마다 동탄성계수를 측정하였다. 실험결과 AE제를 첨가했을 때 물-시멘트비가 적을수록, 폐주물사의 치환율이 클수록 전반적으로 강도가 증가하는 것으로 나타났으며, 물-시멘트비가 증가함에 따라, AE제를 사용한 콘크리트가 동결-융해 저항성이 증가하는 것으로 나타났다. 특히 폐주물사 치환율이 50%일 때가 동결-융해 저항성이 가장 좋은 것으로 나타났으며 그 다음으로 25, 0% 순으로 저항성이 좋은 것으로 나타났다. 따라서 폐주물사 콘크리트가 내구성이 우수한 것으로 나타나 폐주물사를 콘크리트에 재활용 할 수 있는 것으로 나타났다. Concrete structures has been deteriorated by the freezing and thawing due to temperature gap. This study was conducted to evaluate durability of concrete which are increasingly demanded recently. Therefore the research of durability must be executed for application of waste foundry sand concrete real structures. Concrete durability properties incorporating waste foundry sand was performed with the variable of W/C ratio, Sand/Waste foundry sand ratio and Air entrainment-Non air entrainment. Cylinder specimens were made and subjected to freezing and thawing cycle at -18℃ and 4℃. Dynamic modulus of elasticity were evaluated as F/T cycle increase. The results show that strength of concrete is increased the W/C ratio decrease, the Sand/Waste foundry sand ratio increase when the concrete contains AE agent and decreasing W/C ratio and AE concrete makes improved resistance of freezing and thawing improved. Especially, resistance of freezing and thawing is improved by Fine aggregate/Waste foundry sand ratio which is 50%, 25%, 0% in a row. Therefore it is turn out the waste foundry sand could be applied to concrete from the experiment.

Anti-Proliferative Effect of an Aqueous Extract of <i>Prunella vulgaris</i> in Vascular Smooth Muscle Cells

Hwang, Sun Mi,Lee, Yun Jung,Lee, Yong Pyo,Yoon, Jung Joo,Lee, So Min,Cha, Jeong Dan,Choi, Kyung Min,Kang, Dae Gill,Lee, Ho Sub Hindawi Publishing Corporation 2013 Evidence-based Complementary and Alternative Medic Vol.2013 No.-

<P>The abnormal proliferation of vascular smooth muscle cells (VSMCs) in arterial walls is an important pathogenic factor of vascular disorders such as diabetic atherosclerosis. We have reported the anti-inflammatory effect of an aqueous extract from <I>Prunella vulgaris</I> (APV) in vascular endothelial cell. In the present study, APV exhibited inhibitory effects on high glucose-stimulated VSMC proliferation, migration, and invasion activities, inducing G<SUB>1</SUB> cell cycle arrest with downregulation of cyclins and CDKs and upregulation of the CKIs, p21<SUP>waf1/cip1</SUP> and p27<SUP>kip1</SUP>. Furthermore, APV dose dependently suppressed the high glucose-induced matrix metalloproteinase activity. High glucose-induced phosphorylation of ERK, p38 MAPK, was decreased by the pretreatment of APV. NF-<I><I>κ</I></I>B activation by high glucose was attenuated by APV, as an antioxidant. APV attenuated the high glucose-induced decrease of nuclear factor E2-related factor-2 (Nrf2) translocation and heme oxygenase-1 (HO-1) expression. Intracellular cGMP level was also increased by APV treatment. These results demonstrate that APV may inhibit VSMC proliferation via downregulating ROS/NF-<I><I>κ</I></I>B /ERK/p38 MAPK pathways. In addition, APV has a beneficial effect by the interaction of Nrf2-mediated NO/cGMP with HO-1, suggesting that <I>Prunella vulgaris</I> may be useful in preventing diabetic atherosclerosis.</P>

TNF-α로 유도된 혈관내피세포의 혈관염증에 미치는 오적산(五積散)의 억제 효과

한병혁 ( Byung Hyuk Han ),윤정주 ( Jung Joo Yoon ),김혜윰 ( Hye Yoom Kim ),안유미 ( You Mee Ahn ),홍미현 ( Mi Hyeon Hong ),손찬옥 ( Chan Ok Son ),나세원 ( Se Won Na ),이윤정 ( Yun Jung Lee ),강대길 ( Ho Sub Lee ),이호섭 대한본초학회 2018 大韓本草學會誌 Vol.33 No.4

Objectives : Ojeoksan, originally recorded in an ancient Korean medicinal book named “Donguibogam” and has been used for the treatment of circulation disorder of blood which was called blood accumulation (血積) in Korean medicine. Therefore, this study was carried out to investigate the beneficial effect of OJS on vascular inflammation in HUVECs. Methods : We evaluated the effect of OJS on the expression of cell adhesion molecules and protective role in HUVEC stimulated by TNF-α by using Western blot. Results : Pretreatment with OJS decreased the adhesion of HL-60 cells to TNF-α-induced HUVEC. OJS suppressed TNF-α-induced expression level of cell adhesion molecules such as intracellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1(VCAM-1), and endothelial cell selectin (E-selectin). Moreover, OJS significantly decreased TNF-α-induced production of intracellular reactive oxygen species (ROS); and inhibited the phosphorylation of IκB-α in the cytoplasm compared to the experimental group. Pretreatment with OJS inhibited the trans-location of NF-κB p65 to the nucleus. OJS also inhibited phosphorylation of MAPKs compared to the experimental group. OJS significantly increased the protein expression of Nrf2 and HO-1. Conclusions : Ojeoksan has a protective effect on vascular inflammation, and might be a potential therapeutic agent for early atherosclerosis.

만성두통환자에 대한 아로마침의 임상적 연구

정인태,김수영,김건식,이두익,이재동,이윤호,최도영 WHO COLLABORATING CENTRE FOR TRADITIONAL MEDICINE 2004 東西醫學硏究所 論文集 Vol.2004 No.-

Objective : Because the cause and etiology of chronic headache is not yet fully explained, the treatment of this symptom is not simple. This study compares the effects of aroma acupuncture and normal acupuncture applied an chronic headache patients, in order to establish a primary data for further studier of new treatments and developments of new practical acupunctures. Methods : 38 clinical experiment participants were gathered and through a questionnaire patients who experienced headache for more than 4 hours a day and more than 15 days per month were qualified as Chronic Headache patients. The qualified patients were classified in to two groups, aroma acupuncture group(Aroma AT group, n=23) and normal acupuncture group(AT group, n=15). Treatment was applied 2 times a weeks for 8 weeks. The acupoints, GV20, HN23, ST8, HN46, TE17, GB20, LI20, LI11, LI14, ST36, and LR3 were stimulated for 20 minutes in both the groups. The effects of both groups were analyzed using VAS scores and BPI(Brief Pain Inventory). Results : The VAS pain scores improved significantly in both groups. The decrease rate was larger in the Aroma AT group(p<0.05). The BPI scores for the both groups also decrease. The improvement in the Aroma AT group was larger(p<0.05). Conclusion : Aroma acupuncture applied on chronic headache patients showed effects of relieving pain, improving general activities, changing the mood, and improving sleeping behaviors. These effects were analyzed using VAS scores and BPI. The Aroma AT group showed significant changes of VAS and BPI compared to the AT group, suggesting that this new practical acupuncture is very effective when treating chronic headaches. Further researches are needed to evaluate the distinct functional mechanism of aroma acupuncture, but this study is meaningful in the sense that it will act as a fundamental study to build on.