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      • KCI등재

        L-carnitine treatment attenuates renal tubulointerstitial fibrosis induced by unilateral ureteral obstruction

        ( Hai Yan Zhao ),( Hui Ying Li ),( Jian Jin ),( Ji Zhe Jin ),( Long Ye Zhang ),( Mei Ying Xuan ),( Xue Mei Jin ),( Yu Ji Jiang ),( Hai Lan Zheng ),( Ying Shun Jin ),( Yong Jie Jin ),( Bum Soon Choi ) 대한내과학회 2021 The Korean Journal of Internal Medicine Vol.36 No.0

        Background/Aims: Accumulating evidence indicates that L-carnitine (LC) protects against multiorgan damage through its antioxidant properties and preservation of the mitochondria. Little information is available about the effects of LC on renal fibrosis. This study examined whether LC treatment would provide renoprotection in a rat model of unilateral ureteral obstruction (UUO) and in vitro. Methods: Sprague-Dawley rats that underwent UUO were treated daily with LC for 7 or 14 days. The influence of LC on renal injury caused by UUO was evaluated by histopathology, and analysis of gene expression, oxidative stress, mitochondrial function, programmed cell death, and phosphatidylinositol 3-kinase (PI3K)/ AKT/forkhead box protein O 1a (FoxO1a) signaling. In addition, H<sub>2</sub>O<sub>2</sub>-exposed human kidney cells (HK-2) were treated with LC. Results: LC treatment inhibited expression of proinflammatory and profibrotic cytokines, and was followed by a significant attenuation of tubulointerstitial inflammation and fibrosis. The increased oxidative stress caused by UUO was associated with mitochondrial dysfunction and excessive apoptosis and autophagy via PI3K/AKT/FoxO1a-dependent signaling, and this was abrogated by administration of LC. In H<sub>2</sub>O<sub>2</sub>-exposed HK-2 cells, LC decreased intracellular production of reactive oxygen species, and suppressed expression of profibrotic cytokines and reduced the number of apoptotic cells. Conclusions: LC protects against the progression of tubulointerstitial fibrosis in an obstructed kidney.

      • SCIESCOPUSKCI등재

        Structural Requirements of 2',4',6'-Tris(methoxymethoxy) chalcone Derivatives for Anti-inflammatory Activity: The Importance of a 2'-Hydroxy Moiety

        Jin, Feng,Jin, Xing Yu,Jin, Ying Lan,Sohn, Dae-Won,Kim, Soon-Ai,Sohn, Dong-Hwan,Kim, Youn-Chul,Kim, Hak-Sung 대한약학회 2007 Archives of Pharmacal Research Vol.30 No.11

        Butein, a natural chalcone, has anti-inflammatory and hepatoprotective activity. One synthetic derivative of butein, 2',4',6'-tris(methoxymethoxy)chalcone (TMMC), has potent anti-inflammatory activity via an HO-1 (heme oxygenase 1) dependent pathway. The ${\alpha},{\beta}-unsaturated$ ketone moiety in both TMMC and chalcones could be important in mediating this effect. To investigate the structural requirements of TMMC derivatives for anti-inflammatory effects, we modified the ${\alpha},{\beta}-unsaturated$ ketone moiety through catalytic hydrogenation, hydride reduction, or introduction of a triple bond. In addition, we performed structural modifications such as converting the -OMOM group to an -OMe or -OH group. Generally, modifications in the a,_-unsaturated ketone caused a significant decrease or loss of anti-inflammatory activity, which is consistent with the role of the a,_-unsaturated ketone group acting as a Michael acceptor of nucleophilic species like glutathione or cysteine residues on proteins. Chemically, the electron-donating substituents could make the thiol-adduct more stable by decreasing the acidity of the ${\alpha}-hydrogen$ and slowing the speed of the retro-Michael reaction. Also, like previous studies, the 2'-hydroxy group was crucial in increasing the anti-inflammatory effect. The 2'-hydroxy group produced potent anti-inflammatory effects by increasing the electrophilic properties of ${\alpha},{\beta}-unsaturated$ ketones due to hydrogen bonding between the 2'-hydroxy group and the ketone moiety.

      • SCIESCOPUSKCI등재

        Structure Activity Relationship Studies of Anti-inflammatory TMMC Derivatives: 4-Dimethylamino Group on the B Ring Responsible for Lowering the Potency

        Jin, Ying Lan,Jin, Xing Yu,Jin, Feng,Sohn, Dong-Hwan,Kim, Hak-Sung 대한약학회 2008 Archives of Pharmacal Research Vol.31 No.9

        We previously synthesized 2', 4', 6'-tris(methoxymethoxy)chalcone (TMMC) derivatives with various substituents on the A ring that showed potent anti-inflammatory effects by inhibiting NO production in RAW 264.7 cells. The 2'-hydroxy group on the A ring could elevate the electrophilicity of Michael addition of GSH and electron donating groups on the A ring could stabilize the GSH adduct by decreasing the acidity of the $\alpha$-hydrogen. Using this interpretation, we tested various substituents on the B ring and established a proper balance between biological activity and the position of the electron donating or electron withdrawing groups on the B ring. In this case, the 2'-hydroxy group was excluded because it could cause the formation of GSSG through a phenoxy radical and can confuse the interpretation of the biological results. Chalcone derivatives without 2'-hydroxy are likely to deplete cellular GSH levels by a Michael addition process. Strong electron donating groups on the B ring, such as 4-dimethylamino group, gave the weakest inhibition of NO production. A 4-dimethyamino group on the B ring could decrease the stability of the GSH adduct by weakening the C-S bond strength through movement of an electron pair on nitrogen via an aromatic ring.

      • SCOPUSKCI등재

        Synthesis of a Novel Series of Imidazo[1,2-α]pyridines as Acyl-CoA: Cholesterol Acyltransferase (ACAT) Inhibitors

        Jin, Ying-Lan,Rho, Mun-Chual,Gajulapati, Kondaji,Jung, Hwa-Young,Boovanahalli, Shanthaveerappa K.,Lee, Jee-Hyun,Song, Gyu-Yong,Choi, Jung-Ho,Kim, Young-Kook,Lee, Kyeong,Choi, Yong-Seok Korean Chemical Society 2009 Bulletin of the Korean Chemical Society Vol.30 No.6

        A novel series of imidazo[1,2-$\alpha$]pyridines was designed, synthesized, and tested for their ability to inhibit acyl- CoA:cholesterol acyltransferase. Preliminary lead optimization efforts resulted in the identification of ACAT inhibitors represented by analogues 5b, 5c, 6a, 6c, 7b, and 7c. The ACAT inhibitory activity of these compounds was further established by potent inhibition of cholesteryl ester formation in HepG2 cells by a representative analogue 7b.

      • KCI등재

        The Influence of a Second Metal on the Ni/SiC Catalyst for the Methanation of Syngas

        ( Lan Lan Song ),( Yue Yu ),( Xiao Xiao Wang ),( Guoq Jang Jin ),( Ying Yong Wang ),( Xiang Yun Guo ) 한국화학공학회 2014 Korean Chemical Engineering Research(HWAHAK KONGHA Vol.52 No.5

        The catalytic performance of silicon carbide supported nickel catalysts modified with or without secondmetal (Co, Cu and Zn) for the methanation of CO has been investigated in a fixed-bed reactor using a feed consisting of25% CO and 75% H2 without any diluent gas. It has been found that the introduction of Co species can clearly improvethe catalytic activity of Ni/SiC catalyst, whereas the addition of Cu or Zn can result in a significant decrease in the catalyticactivity. The characterizations by means of XRD, TEM, XPS, CO-TPD and H2-TPR indicate that the addition ofCo could decrease the particle size of active metal, increase active sites on the surface of methanation catalyst, improvethe chemisorption of CO and enhance the reducibility of methanation catalysts. Additionally, the special interaction betweenCo species and Ni species is likely favorable for the dissociation of adsorbed CO on the surface of catalyst, and this mayalso contribute to the high activity of 5Co-Ni/SiC catalyst for CO methanation reaction. For 5Cu-Ni/SiC catalyst and 5Zn-Ni/SiC catalyst, Cu and Zn species could cover partial nickel particles and decrease the chemisorption amount of CO. These could be responsible for the low methanation activity. In addition, a 150h stability test under 2 MPa and 300 oCshowed that 5Co-Ni/SiC catalyst was very stable for CO methanation reaction.

      • SCOPUSKCI등재

        Synthesis and Antiviral Activity of Novel 4'-Branched Carbocyclic C-Nucleoside

        Jin, Ying Lan,Hong, Joon-Hee Korean Chemical Society 2005 Bulletin of the Korean Chemical Society Vol.26 No.9

        The first synthesis of a 4'-branched carbocyclic C-nucleoside 11 was achieved via the key intermediate 6, which was prepared using Knovenagel type condensation from ketone derivative 4.

      • SCOPUS

        Synergistic Effects of Leflunomide and Benazepril in Streptozotocin-Induced Diabetic Nephropathy

        Jin, Hua,Piao, Shang Guo,Jin, Ji Zhe,Jin, Ying Shun,Cui, Zhen Hua,Jin, Hai Feng,Zheng, Hai Lan,Li, Jin Ji,Jiang, Yu Ji,Yang, Chul Woo,Li, Can S.Karger 2014 The Nephron Journals Vol.126 No.3

        <P>Abstract</P><P><B><I>Background:</I></B> Leflunomide (LEF) and benazepril have renoprotective effects on diabetic nephropathy (DN) through their anti-inflammatory and anti-fibrotic activities. This study investigated whether combined treatment using LEF and benazepril affords superior protection compared with the respective monotherapies. <B><I>Methods:</I></B> Diabetes was induced with streptozotocin (STZ, 65 mg/kg) by intraperitoneal injection in male Wistar rats. Two weeks after STZ injection, diabetic rats were treated daily for 12 weeks with LEF (10 mg/kg), benazepril (10 mg/kg), or a combination of both. Basic parameters (body weight, fasting blood glucose level, and 24 h urinary protein excretion), histopathology, inflammatory [inflammatory cell infiltration (ED-1), monocyte chemoattractant protein-1 (MCP-1), and Toll-like receptor-2 (TLR-2)] and glomerulosclerotic factors [transforming growth factor-β<SUB>1</SUB> (TGF-β<SUB>1</SUB>) and connective tissue growth factor (CTGF)], and oxidative stress (8-hydroxy-2'-deoxyguanosine, 8-OHdG) were studied. <B><I>Results:</I></B> Benazepril or LEF treatment significantly prevented body weight loss and 24 h urinary protein excretion induced by diabetes; combined treatment with LEF and benazepril further improved these parameters compared with giving each drug alone (all p < 0.01). Increased expression of inflammatory (MCP-1 and TLR-2) and glomerulosclerotic (TGF-β<SUB>1</SUB> and CTGF) factors in diabetic rat kidney was reduced by treatment with either LEF or benazepril and was further reduced by the combined administration of the two drugs (p < 0.01). These effects were accompanied by suppression of urinary 8-OHdG excretion. There was no significant between-group difference in blood glucose level. <B><I>Conclusions:</I></B> LEF treatment lessens DN, and combined treatment with LEF and benazepril provides synergistic effects in preventing DN.</P><P>© 2014 S. Karger AG, Basel</P>

      • KCI등재

        Structure Activity Relationship Studies of Anti-inflammatory TMMC Derivatives: 4-Dimethylamino Group on the B Ring Responsible for Lowering the Potency

        Ying Lan Jin,Xing Yu Jin,Feng Jin,손동환,김학성 대한약학회 2008 Archives of Pharmacal Research Vol.31 No.9

        We previously synthesized 2’,4’,6’-tris(methoxymethoxy)chalcone (TMMC) derivatives with various substituents on the A ring that showed potent anti-inflammatory effects by inhibiting NO production in RAW 264.7 cells. The 2’-hydroxy group on the A ring could elevate the electrophilicity of Michael addition of GSH and electron donating groups on the A ring could stabilize the GSH adduct by decreasing the acidity of the α-hydrogen. Using this interpretation, we tested various substituents on the B ring and established a proper balance between biological activity and the position of the electron donating or electron withdrawing groups on the B ring. In this case, the 2’-hydroxy group was excluded because it could cause the formation of GSSG through a phenoxy radical and can confuse the interpretation of the biological results. Chalcone derivatives without 2’-hydroxy are likely to deplete cellular GSH levels by a Michael addition process. Strong electron donating groups on the B ring, such as 4-dimethylamino group, gave the weakest inhibition of NO production. A 4-dimethyamino group on the B ring could decrease the stability of the GSH adduct by weakening the C-S bond strength through movement of an electron pair on nitrogen via an aromatic ring.

      • KCI등재

        Structural Requirements of 2',4',6'-Tris(methoxymethoxy)chalcone Derivatives for Anti-inflammatory Activity: The Importance of a 2'-Hydroxy Moiety

        Feng Jin,Xing Yu Jin,Ying Lan Jin,Dae Won Sohn,김순애,손동환,Youn Chul Kim,Hak Sung Kim 대한약학회 2007 Archives of Pharmacal Research Vol.30 No.11

        Butein, a natural chalcone, has anti-inflammatory and hepatoprotective activity. One synthetic derivative of butein, 2',4',6'-tris(methoxymethoxy)chalcone (TMMC), has potent anti-inflammatory activity via an HO-1 (heme oxygenase 1) dependent pathway. The α,β-unsaturated ketone moiety in both TMMC and chalcones could be important in mediating this effect. To investigate the structural requirements of TMMC derivatives for anti-inflammatory effects, we modified the α,β-unsaturated ketone moiety through catalytic hydrogenation, hydride reduction, or introduction of a triple bond. In addition, we performed structural modifications such as converting the -OMOM group to an -OMe or -OH group. Generally, modifications in the α,β-unsaturated ketone caused a significant decrease or loss of anti-inflammatory activity, which is consistent with the role of the α,β-unsaturated ketone group acting as a Michael acceptor of nucleophilic species like glutathione or cysteine residues on proteins. Chemically, the electron-donating substituents could make the thiol-adduct more stable by decreasing the acidity of the α-hydrogen and slowing the speed of the retro-Michael reaction. Also, like previous studies, the 2'- hydroxy group was crucial in increasing the anti-inflammatory effect. The 2'-hydroxy group produced potent anti-inflammatory effects by increasing the electrophilic properties of α,β-unsaturated ketones due to hydrogen bonding between the 2'-hydroxy group and the ketone moiety.

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