Synthetic Wogonin Derivatives Suppress Lipopolysaccharide-Induced Nitric Oxide Production and Hydrogen Peroxide-Induced Cytotoxicity

Chun Wanjoo,Lee Hee Jae,Kong Pil-Jae,Lee Gun Hee,Cheong Il-Young,Park Haeil,Kim Sung-Soo The Pharmaceutical Society of Korea 2005 Archives of Pharmacal Research Vol.28 No.2

Wogonin (5,7-dihydroxy-8-methoxyflavone) has been reported to exhibit a variety of biological properties including anti-inflammatory and neuroprotective functions. In this study, biological activities of diverse synthetic wogonin derivatives have been evaluated in two experimental cell culture models. Inhibitory activities of wogonin derivatives on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in BV2 microglial cells and on hydrogen peroxide ($H_{2}O_2$)-induced neuronal cell death in SH-SY5Y human neuroblastoma were examined. Wogonin derivatives such as WS2 and WS3 showed more potent suppressive activities on LPS-induced NO production and $H_{2}O_2$-induced cytotoxicity than wogonin itself. In addition, thiol substitution played a minor role in enhancing the activities of the derivatives. These findings may contribute to the development of novel anti-inflammatory and neuroprotective agents derived from wogonin.

Therapeutic Intervention of Aggregate Formation in Huntington's Disease : A Potential Role of Tissue Transglutaminase (tTG)

Wanjoo Chun 大韓藥學會 2003 大韓藥學會 總會 및 學術大會 Vol.2003 No.1

Synthetic Wogonin Derivatives Suppress Lipopolysaccharide-Induced Nitric Oxide Production and Hydrogen Peroxide-Induced Cytotoxicity

Wanjoo Chun,Hee Jae Lee,Pil-Jae Kong,Gun Hee Lee,Il-Young Cheong,Haeil Park,Sung-Soo Kim 대한약학회 2005 Archives of Pharmacal Research Vol.28 No.2

Wogonin (5,7-dihydroxy-8-methoxyflavone) has been reported to exhibit a variety of biological properties including anti-inflammatory and neuroprotective functions. In this study, biological activities of diverse synthetic wogonin derivatives have been evaluated in two experimental cell culture models. Inhibitory activities of wogonin derivatives on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in BV2 microglial cells and on hydrogen peroxide (H2O2)-induced neuronal cell death in SH-SY5Y human neuroblastoma were examined. Wogonin derivatives such as WS2 and WS3 showed more potent suppressive activities on LPS-induced NO production and H2O2-induced cytotoxicity than wogonin itself. In addition, thiol substitution played a minor role in enhancing the activities of the derivatives. These findings may contribute to the development of novel anti-inflammatory and neuroprotective agents derived from wogonin.

3,4,5-Trihydroxycinnamic acid attenuates lipopolysaccharide (LPS)-induced acute lung injury <i>via</i> downregulating inflammatory molecules and upregulating HO-1/AMPK activation

Lee, Jae-Won,Chun, Wanjoo,Kwon, Ok-Kyoung,Park, Hyun Ah,Lim, Yourim,Lee, Jae-Hyeon,Kim, Doo-Young,Kim, Jung Hee,Lee, Hyeong-Kyu,Ryu, Hyung Won,Oh, Sei-Ryang,Ahn, Kyung-Seop Elsevier 2018 INTERNATIONAL IMMUNOPHARMACOLOGY Vol.64 No.-

<P><B>Abstract</B></P> <P>The increase in inflammatory cytokines and chemokines is a common denominator in the pathogenesis of acute lung injury (ALI) which are involved in the influx of inflammatory cells and lung damage. The aim of the present study was to evaluate the protective effect of 3,4,5-trihydroxycinnamic acid (THC) in lipopolysaccharide (LPS)-induced ALI. THC efficiently decreased the mRNA expression of interleukin-8 (IL-8) in LPS-stimulated A549 airway epithelial cells. THC induced heme oxygenase-1 (HO-1) expression in A549 cells. THC also increased the activation of AMP-activated protein kinase (AMPK) in A549 cells and RAW264.7 macrophages. In LPS-induced ALI in mice, THC significantly suppressed neutrophil influx and monocyte chemoattractant protein-1 (MCP-1) production in the bronchoalveolar lavage fluid (BALF). THC also attenuated the levels of neutrophil elastase (NE), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the BALF and serum. In addition, THC inhibited the expressions of inducible nitric oxide synthase (iNOS) and the activation of nuclear factor-kappa B (NF-κB) in the lung. These protective effects of THC were accompanied with HO-1 induction and AMPK activation. Taken together, the present study clearly demonstrates that THC significantly attenuates the LPS-induced ALI, suggesting that THC might be a valuable therapeutic adjuvant in airway inflammatory disorders.</P> <P><B>Highlights</B></P> <P> <UL> <LI> THC reduces the mRNA expression of IL-8 in LPS-stimulated A549 airway epithelial cells. </LI> <LI> THC inhibits the influx of neutrophils and macrophages in the BALF of ALI mice. </LI> <LI> THC decreases the levels of NE, TNF-α and IL-6 in the BALF and serum. </LI> <LI> THC attenuates the recruitment of inflammatory cells and the production of MCP-1 in the lung. </LI> <LI> THC downregulates the activation of NF-κB and upregulates the activation of HO-1 and AMPK in the lung. </LI> </UL> </P>

Curcumin Attenuates Glial Cell Activation But Cannot Suppress Hippocampal CA3 Neuronal Cell Death in i.c.v. Kanic Acid Injection Model

Jaeyoung Cho,Pil-Jae Kong,Wanjoo Chun,Yeo-Ok Moon,Yee-Tae Park,So-Young Lim,Sung-Soo Kim 대한생리학회-대한약리학회 2003 The Korean Journal of Physiology & Pharmacology Vol.13 No.4

Kainic acid (KA) is a structural analogue of glutamate that interacts with specific presynaptic and postsynaptic receptors to potentiate the release and excitatory actions of glutamate. Systemic or intracerebroventricular (i.c.v.) administration of KA to experimental animals elicits multifocal seizures with a predominantly limbic localization, and results in neuronal death of cornu ammonia 1 (CA1), reactive gliosis and biochemical changes in the hippocampus and other limbic structures. Several lines of evidence suggest that reactive oxygen species (ROS) play a pivotal role in the pathogenesis of excitotoxic death by KA. Curcumin has been known to possess anti-oxidative and anti-inflammatory activities. In this study, the effects of curcumin on KA induced hippocampal cell death, reactive gliosis and biochemical changes in reactive glia were investigated by immunohistochemical methods. Our data demonstrated that curcumin attenuated KA-induced astroglial and microglial activation although it did not protect KA-induced hippocampal cell death.

Sequestration of sorcin by aberrant forms of tau results in the defective calcium homeostasis

Kim, Song-In,Lee, Hee Jae,Kim, Sung-Soo,Kwon, Yong-Soo,Chun, Wanjoo The Korean Society of Pharmacology 2016 The Korean Journal of Physiology & Pharmacology Vol.20 No.4

Neurofibrillary tangles (NFTs) of microtubule-associated protein tau are a pathological hallmark of Alzheimer's disease (AD). Endoplasmic reticulum (ER) stress has been known to be involved in the pathogenesis of AD. However, the exact role of ER stress in tau pathology has not yet been clearly elucidated. In present study, the possible relationship between tau pathology and ER stress was examined in terms of sorcin, which is a calcium binding protein and plays an important role in calcium homeostasis. Our previous yeast two hybrid study showed that sorcin is a novel tau interacting protein. Caspase-3-cleaved tau (T4C3) showed significantly increased tau-sorcin interaction compared to wild type tau (T4). Thapsigargin-induced ER stress and co-expression of constitutively active $GSK3{\beta}$ ($GSK3{\beta}-S9A$) also exhibited significantly increased tau-sorcin interactions. T4C3-expressing cells showed potentiated thapsigargin -induced apoptosis and disruption of intracellular calcium homeostasis compared to T4-expressing cells. Overexpression of sorcin significantly attenuated thapsigargin-induced apoptosis and disruption of calcium homeostasis. In contrary, siRNA-mediated knock-down of sorcin showed significantly increased thapsigargin-induced apoptosis and disruption of calcium homeostasis. These data strongly suggest that sequestration of sorcin by aberrant forms of tau compromises the function of sorcin, such as calcium homeostasis and cellular resistance by ER stress, which may consequently result in the contribution to the progression of AD.

The Cytotoxicity of Kahweol in HT-29 Human Colorectal Cancer Cells Is Mediated by Apoptosis and Suppression of Heat Shock Protein 70 Expression

( Dong Wook Choi ),( Man Sup Lim ),( Jae Won Lee ),( Wanjoo Chun ),( Sang Hyuk Lee ),( Yang Hoon Nam ),( Jin Myung Park ),( Dae Hee Choi ),( Chang Don Kang ),( Sung Joon Lee ),( Sung Chul Park ) 한국응용약물학회 2015 Biomolecules & Therapeutics(구 응용약물학회지) Vol.23 No.2

Although coffee is known to have antioxidant, anti-inflammatory, and antitumor properties, there have been few reports about the effect and mechanism of coffee compounds in colorectal cancer. Heat shock proteins (HSPs) are molecular chaperones that prevent cell death. Their expression is significantly elevated in many tumors and is accompanied by increased cell proliferation, metastasis and poor response to chemotherapy. In this study, we investigated the cytotoxicity of four bioactive compounds in coffee, namely, caffeine, caffeic acid, chlorogenic acid, and kahweol, in HT-29 human colon adenocarcinoma cells. Only kahweol showed significant cytotoxicity. Specifically, kahweol increased the expression of caspase-3, a pro-apoptotic factor, and decreased the expression of anti-apoptotic factors, such as Bcl-2 and phosphorylated Akt. In addition, kahweol significantly attenuated the expression of HSP70. Inhibition of HSP70 activity with triptolide increased kahweol-induced cytotoxicity. In contrast, overexpression of HSP70 significantly reduced kahweol-induced cell death. Taken together, these results demonstrate that kahweol inhibits colorectal tumor cell growth by promoting apoptosis and suppressing HSP70 expression.

Association of GnRH1 Polymorphisms with Rheumatoid Arthritis in a Korean Female

Yu Mi Kim(김유미),Kye Young Han(한계영),Eun Bi Kwak(곽은비),Wanjoo Chun(전완주),Sung Soo Kim(김성수),Hee Jae Lee(이희제) 대한정형외과학회 2010 대한정형외과학회지 Vol.45 No.5

목적: 류마티스 관절염(RA)의 병태생리에 대해 아직 명확하게 밝혀져 있지 않으나 일부의 경우 유전적 요인이 류마티스 관절염의 발생에 영향을 주는 것으로 알려져 있다. 역학조시 결과 여성이 남성보다 류마티스성 관절염의 유병률이 3배 정도 높다. Gonadal 호르몬들은 면역체계나 자가면역질환에서 성에 따른 이형을 나타내는데 영향을 주는 것으로 알려져 있다. 이 가운데 gonadotrophin-releasing hormone (GnRH)는 면역 시스템을 조절하는 데도 중요한 역할을 한다. 따라서,GnRH가 류마티스 관절염에서 성적 차이를 나타내는데 중요한 역할을 할 수 있으며 이를 증명하기 위해 GnRH1 유전자를 후보 유전자로 선택하고 이들 유전자 내의 단일염기다형성(SNP)을 분석함으로써,RA와 GnRHl 유전자 다형성과의 연관성에 대해 연구하고자 하였다. 대상 및 방법: 153명의 RA 여성 환자와 96명의 정상 대조군을 대상으로, GnHR1 유전자 내의 5개의 SNP, rs2659590, rs2321248, rs6186, rs6185, rs2321049의 유전자형과 대립유전자형의 빈도를 비교 분석하였다. 또한 RA 환자들을 erythrocyte sedimentation rate (ESR)과 골 미란 유무에 따라 나누고 GnRH1 SNP과의 연관성을 확인하였다. 결과: 한국인 여성 RA 환자들과 정상군들 사이에서 GnRH1 SNP들의 유전자형과 대립유전자들의 빈도는 유의한 차이가 없었다. 하지만, rs2659590, rs6185, rs2321248에서 ESR이 30 이상인 환자와 30 미만 환자 사이에 로지스퇴 회귀 분석 결과 유의한 상관관계가 나타났다. 하지만, 골 미란 유무는 연관성이 없었다. 결론: 본 연구에서 RA와 GnRH1 유전자 다형성 사이의 연관성은 보여주지 못하였지만, ESR의 수치와 GnRH1 유전자 다형성 간에 연관성을 보였다. 비록 그 수가 적어 제한적인 의미를 가질 수 있으나 처음으로 GnRH1 유전자의 다형성과 RA환자의 ESR 간의 연관 가능성을 시사하는데 의의가 있다. Purpose: Rheumatoid arthritis (RA) is a common, chronic inflammatory arthritis that develops most often in women. Gonadal hormones may account for the sexual dimorphism in the immune response and for the greater incidence of autoimmune disease in females. Gonadotrophin- releasing hormone (GnRH), one of the gonadal hormones, plays an important role in immune system modulation. This study examined the effects of single nucleotide polymorphisms (SNP) in GnRH on gender differences in the pathophysiology of RA. Materials and Methods: The presence of SNPs rs2659590, rs2321248, rs6186, rs6185, and rs2321 049 in the human GnRH1 gene was confirmed in Korean RA patients by Taqman" SNP genotyping assays A total of 153 unrelated female, Korean RA patients and 96 female Korean controls participated. Results: There were no significant associations between GnRH1 polymorph isms and RA. However, we found that the rs2659590, rs6185 and rs2321248 polymorphism might be associated with a susceptibility to aberrantly high erythrocyte sedimentation rates in female RA patients. Conclusion: Additional studies, with a larger number of patients and in different populations will be required to assess whether GnRH1 polymorph isms and these haplotypes could be used as susceptibility or resistance markers in RA. To our knowledge, this study is the first to analyze associations between SNPs of GnRH1 and RA.

Inhibitory Effects of an Aqueous Extract of Gynura procumbens on Human Mesangial Cell Proliferation

Hee Jae Lee,Byung-Cheol Lee,Joo-Ho Chung,Sumali Wiryowidagdo,Wanjoo Chun,Sung-Soo Kim,Hyunsook Kim,Myeon Choe 대한생리학회-대한약리학회 2007 The Korean Journal of Physiology & Pharmacology Vol.20 No.3

<I>Gynura procumbens</I> (Lour.) Merr. has been used in some parts of Southeast Asia as a folk medicine to treat kidney diseases, diabetes mellitus, and hyperlipidemia. The present work was undertaken to prove the mechanisms of <I>G. procumbens</I> in the management of glomerular diseases. We investigated the effect of an aqueous extract of G. procumbens on cell proliferation, DNA synthesis, and the expressions of TGF-β1, <I>PDGF-BB, CDK1, CDK2, </I>and CDK4 in fetal bovine serum-activated human mesangial cells (MCs). The G. procumbens extract inhibited proliferation, DNA synthesis, expressions of <I>PDGF-BB, CDK1,</I> and <I>CDK2 </I>mRNA, and expression of TGF-β1 protein in MCs. The inhibitory effect of G. procumbens on MC proliferation may be mediated by suppression of PDGF-BB and TGF-β1 expressions and the modulation of <I>CDK1 </I>and <I>CDK2</I> expression. Therefore, <I>G. procumbens </I>shows promise as an adjunct therapy in preventing progressive renal diseases.

Decreased Expression of PTEN in Olfactory Bulb of Rat Pub after Naris Closure

Jaeyoung Cho,Sang-Hyun Lee,Geon Hee Lee,Wanjoo Chun,Yee-Tae Park 대한생리학회-대한약리학회 2004 The Korean Journal of Physiology & Pharmacology Vol.8 No.1

PTEN (phosphatase and tensin homolog) is a dual specific phosphatase antagonizing phosphoinositide 3-kinase activity, and has first been cloned as a tumor suppressor for glioma. Although the role of PTEN as a tumor suppressor has been well studied, little is known about signaling mechanisms regulating expression and/or activity of PTEN in the central nervous system. In this study, we investigated whether PTEN expression is regulated by sensory deprivation. P5 rat pups were unilaterally naris-closed, and olfactory bulbs were immunohistochemically analyzed with PTEN antibody at the 7<SUP>th</SUP> day after naris closure. PTEN immunoreactivity was found to be down-regulated in both glomerular, external plexiform and subependymal cell layers, suggesting that odor deprivation signals down-regulate expression of PTEN in the olfactory bulb. To the best of our knowledge, this is the first report to suggest that PTEN expression is regulated by sensory deprivation signals in neonatal rats.