연잎, 연자육, 연자방 에탄올 추출물의 항염증 활성

이은주(Eun-Joo Lee),서유미(Yu-Mi Seo),김용현(Yong-Hyun Kim),정정욱(Chungwook Chung),성화정(Hwa-Jung Sung),손호용(Ho-Yong Sohn),박종이(Jong-Yi Park),김종식(Jong-Sik Kim) 한국생명과학회 2019 생명과학회지 Vol.29 No.4

연은 아시아 국가에서 음식과 약재로 널리 사용되는 재료이다. 본 연구에서는 연의 잎(leaf, NL), 자육(seed, NS), 자방(seedpod, NSP)으로부터 에탄올 추출물을 제조하고 이들의 항염증 활성과 작용기전을 규명하였다. 이들의 항염증 활성을 연구하기 위하여 LPS로 자극된 RAW 264.7 세포에서 nitric oxide (NO) 생산을 측정하였다. NL, NS, NSP는 세포 생존율에 영향을 주지 않으면서, 농도의존적으로 NO의 생산을 현저하게 저해하였으며, iNOS 및 COX-2와 같은 pro-inflammatory 중재자들의 단백질 발현을 감소시켰다. 또한, NL, NS, NSP는 MAPKs 단백질의 인신화를 감소시키고 NF-κB p65의 핵으로의 이동을 저해함으로써, 세 추출물에 의한 항염증 활성은 MAPKs 경로와 NF-κB 경로를 조절함으로써 이루어짐을 제시한다. 게다가, ROS의 생성이 세 추출물에 의해서 모두 저해되었으며, HO-1의 발현과 HO-1의 전사조절인자인 Nrf2의 핵으로의 이동이 증가되었다. 결론적으로, 이러한 연구결과는 연의 다양한 부위의 추출물인 NL, NS 그리고 NSP는 항염증 활성을 가지고 있으며, MAPKs, NF-κB, Nrf2/HO-1 등 다양한 신호경로를 통해 조절할 수 있음을 제시한다. Nelumbo nucifera, also known as sacred lotus, has mainly been used as a food throughout the Asian countries. In the present study, we prepared ethanol extracts from leaf (NL), seed (NS), and seedpod (NSP) of Nelumbo nucifera and investigated their anti-inflammatory activities in mouse macrophage RAW 264.7 cells. To evaluate the anti-inflammatory activities of NL, NS, and NSP, nitric oxide (NO) production was measured in LPS-stimulated RAW 264.7 cells. NL, NS, and NSP significantly reduced NO production in a dose-dependent manner without affecting cell viabilities. NL, NS, and NSP dramatically decreased the protein expression of pro-inflammatory genes such as iNOS and COX-2. NL, NS, and NSP also suppressed phosphorylation of MAPKs and the nuclear translocation of NF-κB p65 indicating they have their anti-inflammatory activities via regulating mitogen-activated protein kinases (MAPKs) and nuclear factor kappa B (NF-κB) pathways. In addition, we analyzed the production of reactive oxygen species (ROS) by the treatment of NL, NS, and NSP. All extracts reduced ROS production in a dose-dependent manner. And also, they increased heme oxygenase-1 (HO-1) protein expression and the nuclear translocation of nuclear respiratory factor 2 (Nrf2). In conclusion, our results suggest that Nelumbo nucifera has its anti-inflammatory activity via regulating MAPKs, NF-κB, and Nrf2/HO-1 pathways.

건조 상추 에탄올 추출물의 항염증 활성

이은주(Eun-Joo Lee),서유미(Yu-Mi Seo),김용현(Yong-Hyun Kim),정정욱(Chungwook Chung),성화정(Hwa-Jung Sung),손호용(Ho-Yong Sohn),박종이(Jong-Yi Park),김종식(Jong-Sik Kim) 한국생명과학회 2019 생명과학회지 Vol.29 No.3

상추는 가장 선호하는 녹색 채소 중 하나이다. 상추는 폴리페놀성 화합물을 비롯한 다양한 성분을 함유하고 있으며, 항균, 항산화, 항염증 등의 생리활성을 가지고 있는 것으로 알려져 있다. 본 연구에서는 건조상추의 에탄올 추출물(DLE)을 제조하고 이들의 항염증 활성을 연구하였다. DLE의 항염증 활성을 측정하기 위하여 LPS로 활성화된 마우스 대식세포 RAW 264.7 세포주에서 nitric oxide (NO) 생성을 측정하였다. DLE는 세포주의 생존에는 영향을 미치지 않으면서 NO 생산을 현저하게 저해하였다. DLE에 의해 염증 유전자인 iNOS와 COX-2의 유전자와 단백질의 발현이 모두 감소하였으며, 6개의 염증관련 cytokine 유전자(IL-1α, IL-1β, IL-1F6, TNF-α, CSF2, 그리고 CXCL10)의 발현이 모두 감소하였다. 또한, DLE의 처리는 MAPKs 경로의 인산화를 모두 저해하였으며, NF-κB p65의 핵으로의 이동을 저해하였다. 이러한 결과는 DLE의 항염증 활성은 MAPKs 경로와 NF-κB 경로를 조절함으로써 이루어짐을 시사한다. 또한, DLE는 농도의존적으로 reactive oxygen species (ROS)의 생산을 저해하였으며, hemeoxygenase-1 (HO-1) 단백질의 발현을 증가시켰으며, HO-1의 전사조절인자인 Nrf2의 핵으로의 이동을 증가시켰다. 결론적으로, 이러한 연구결과는 DLE가 염증관련 유전자의 발현을 감소시키며, MAPKs, NF-κB, 그리고 Nrf2/HO-1 등 다양한 경로를 조절함으로써 항염증 활성을 가지는 것을 제시한다. Lettuce (Lactuca sativa L.) is one of the most popular green leafy vegetables, and it contains various beneficial components including polyphenolic compounds and has been known to possess various biological functions such as anti-microbial, anti-oxidative, and anti-inflammatory activities. In the present study, we prepared ethanol extract of dried lettuce (DLE) and investigated its anti-inflammatory activity. To evaluate the anti-inflammatory activity of DLE, nitric oxide (NO) production was measured in LPS-activated mouse macrophage RAW 264.7 cells. DLE significantly suppressed NO production in these cells without affecting cell viabilities while resveratrol was used as a positive control. DLE dramatically decreased the expression of pro-inflammatory genes such as iNOS and COX-2 at the mRNA and protein levels and reduced the expression of several cytokines including IL-1α, IL-1β, IL-1F6, TNF-α, CSF2 and CXCL10. In addition, DLE suppressed phosphorylation of MAPKs and the nuclear translocation of NF-κB p65 indicating DLE shows its anti-inflammatory activity via regulating MAPKs pathway and NF-κB pathways. And also, DLE reduced the production of reactive oxygen species in a dose-dependent manner. DLE increased HO-1 protein expression, and also increased the nuclear translocation of Nrf2. Overall, our results suggest that lettuce down-regulate various pro-inflammatory genes and have its anti-inflammatory activity via regulating MAPKs, NF-κB, and Nrf2/HO-1 pathways.

에탄올이 백서의 해마에서 Neuropeptide Y 발현에 미치는 영향

정홍경,이기철,이정호,이희제,정주호,이주영 대한생물치료정신의학회 2002 생물치료정신의학 Vol.8 No.1

<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>

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.

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>

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>

Neuroprotective mechanisms of dieckol against glutamate toxicity through reactive oxygen species scavenging and nuclear factor-like 2/heme oxygenase-1 pathway

Cui, Yanji,Amarsanaa, Khulan,Lee, Ji Hyung,Rhim, Jong-Kook,Kwon, Jung Mi,Kim, Seong-Ho,Park, Joo Min,Jung, Sung-Cherl,Eun, Su-Yong The Korean Society of Pharmacology 2019 The Korean Journal of Physiology & Pharmacology Vol.23 No.2

Glutamate toxicity-mediated mitochondrial dysfunction and neuronal cell death are involved in the pathogenesis of several neurodegenerative diseases as well as acute brain ischemia/stroke. In this study, we investigated the neuroprotective mechanism of dieckol (DEK), one of the phlorotannins isolated from the marine brown alga Ecklonia cava, against glutamate toxicity. Primary cortical neurons ($100{\mu}M$, 24 h) and HT22 neurons (5 mM, 12 h) were stimulated with glutamate to induce glutamate toxic condition. The results demonstrated that DEK treatment significantly increased cell viability in a dose-dependent manner ($1-50{\mu}M$) and recovered morphological deterioration in glutamate-stimulated neurons. In addition, DEK strongly attenuated intracellular reactive oxygen species (ROS) levels, mitochondrial overload of $Ca^{2+}$ and ROS, mitochondrial membrane potential (${\Delta}{\Psi}_m$) disruption, adenine triphosphate depletion. DEK showed free radical scavenging activity in the cell-free system. Furthermore, DEK enhanced protein expression of heme oxygenase-1 (HO-1), an important anti-oxidant enzyme, via the nuclear translocation of nuclear factor-like 2 (Nrf2). Taken together, we conclude that DEK exerts neuroprotective activities against glutamate toxicity through its direct free radical scavenging property and the Nrf-2/HO-1 pathway activation.

한국인 직무 스트레스 측정도구의 개발 및 표준화

장세진,고상백,강동묵,김성아,강명근,이철갑,정진주,조정진,손미아,채창호,김정원,김정일,김형수,노상철,박재범,우종민,김수영,김정연,하미나,박정선,이경용,김형렬,공정옥,김인아,김정수,박준호,현숙정,손동국 大韓産業醫學會 2005 대한직업환경의학회지 Vol.17 No.4

Background and Purposes: Over the past three decades, numerous studies performed in Korea have reported that job stress is a determinant risk factor for chronic diseases and work disability. Every society has its own culture and occupational climate particular to their organizations, and hence experiences different occupational stress. An occupational stress measurement tool therefore needs to be developed to estimate it objectively. The purpose of this study is to develop and standardize the Korean Occupational Stress Scale (KOSS) which is considered to be unique and specific occupational stressors in Korean employees. Subjects and Methods: Data were obtained from the National Study for Development and Standardization of Occupational Stress (NSDSOS Project: 2002-2004). A total of 12,631 employees from a nationwide sample proportional to the Korean Standard Industrial Classification and the Korean Standard Occupational Classification were administered. The KOSS was developed for 2 years (2002-2004). In the first year, we collected 255 items from the most popular job stress measurement tools such as JCQ, ERI, NIOSH and OSI, and 44 items derived from the a qualitative study (depth interview). Forty-three items of KOSS, in the second year, were retained for use in the final version of the KOSS by using Delphi and factor analysis. Items were scored using conventional 1-2-3-4 Likert scores for the response categories. Results: We developed eight subscales by using factor analysis and validation process: physical environment (3 items), job demand (8 items), insufficient job control (5 items), interpersonal conflict (4 items), job insecurity (6 items), organizational system (7 items), lack of reward (6 items), and occupational climate (4 items). Together they explained 50.0% of total variance. Internal consistency alpha scores were ranged from 0.51 to 0.82. Twenty-four items of the short form of the KOSS (KOSS-SF) were also developed to estimate job stress in the work setting. Because the levels of the subscales of occupational stress were gender dependent, gender-specific standard norms for both the 43-item full version and the 24-item short form using a quartile for the subscales of KOSS were presented. Conclusion: The results of this study suggest that KOSS might be an appropriate measurement scale to estimate occupational stress of Korean employees. Further and more detailed study needs to be conducted to improve the validity of this scale.

서울의 PPNG 발생 빈도(1991-1992)

김재홍,윤기범,박평원,김영진,전경민,김영태,김중환,곽호,구상완,송민석,유옥,지혜구,김동원,문상은,박영립,정승호,성범진,성순제,엄주용,황정열,이기홍,이주협,전태진 대한화학요법학회 1994 대한화학요법학회지 Vol.12 No.1

The prevalence of PPNG among pretreated gonorrhea cases isolated at the STD clinic of Choong-Ku Public Health Center in Seoul has been studied and reported annually since 1981. In 1991, 123 strains of N.gonorrhoeae were isolated, among which 58(47.1%) were PPNG. In 1992, 98 starains of N.gonorrhoeae were isolated, among which 51(52.0%) were PPNG. In all, 109(49.3%) strains were found to be PPNG among 221 strains isolated between 1991-1992. The prevalence of PPNG in Seoul showed increased tendency till 1989, thereafter, it has been stationary or slightly decreasing.