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.

Enhanced development of porcine embryos cloned from bone marrow mesenchymal stem cells

Jin, Hai-feng,Kumar, B Mohana,Kim, Jung-Gon,Song, Hye-Jin,Jeong, Yeon-Ji,Cho, Seong-Keun,Balasubramanian, Sivasankaran,Choe, Sang-Yong,Rho, Gyu-Jin UPV/EHU Press 2007 The international journal of developmental biology Vol.51 No.1

<P>In the present study, we have characterized an isolated population of porcine bone marrow mesenchymal stem cells (MSCs) for multilineage commitment and compared the developmental potential of cloned embryos with porcine MSCs and fetal fibroblasts (FFs). MSCs exhibited robust alkaline phosphatase activity and later transformed into mineralized nodules following osteoinduction. Furthermore, MSCs underwent adipogenic and chondrogenic differentiation by producing lipid droplets and proteoglycans, respectively. Primary cultures of FFs from a female fetus at ~30 day of gestation were established. Donor cells at 3-4 passage were employed for nuclear transfer (NT). Cell cycle analysis showed that the majority of MSCs in confluence were in the G0/G1 stage. Cumulus-oocyte complexes were matured and fertilized in vitro (IVF) as control. The cleavage rate was significantly (P<0.05) higher in IVF than in NT embryos with MSCs and FFs (84.54.6% vs. 52.25.4% and 50.85.2%, respectively). However, blastocyst rates in IVF and NT embryos derived from MSCs (20.62.5% and 18.43.0%) did not differ, but were significantly (P<0.05) higher than NT derived from FFs (9.52.1%). Total cell number and the ratio of ICM to total cells among blastocysts cloned from MSCs (34.45.2 and 0.380.08, respectively) were significantly (P<0.05) higher than those from FFs (22.65.5 and 0.180.12, respectively). Proportions of TUNEL positive cells in NT embryos from FFs (7.31.8%) were significantly (P<0.05) higher than in MSCs (4.61.3%) and IVF (2.50.9%). The results clearly demonstrate that multipotent bone marrow MSCs have a greater potential as donor cells than FFs in achieving enhanced production of cloned porcine embryos.</P>

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.

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>

Kinetics of a Cloned Special Ginsenosidase Hydrolyzing 3-O-Glucoside of Multi-Protopanaxadiol-Type Ginsenosides, Named Ginsenosidase Type 3

( Xue Feng Jin ),( Hong Shan Yu ),( Dong Ming Wang ),( Ting Qiang Liu ),( Chun Ying Liu ),( Dong Shan An ),( Wan Taek Im ),( Song Gun Kim ),( Feng Xie Jin ) 한국미생물 · 생명공학회 2012 Journal of microbiology and biotechnology Vol.22 No.3

In this paper, the kinetics of a cloned special glucosidase, named ginsenosidase type III hydrolyzing 3-O-glucoside of multi-protopanaxadiol (PPD)-type ginsenosides, were investigated. The gene (bgpA) encoding this enzyme was cloned from a Terrabacter ginsenosidimutans strain and then expressed in E. coli cells. Ginsenosidase type III was able to hydrolyze 3-O-glucoside of multi-PPD-type ginsenosides. For instance, it was able to hydrolyze the 3- O-β-D-(1→2)-glucopyranosyl of Rb1 to gypenoside XVII, and then to further hydrolyze the 3-O-β-D-glucopyranosyl of gypenoside XVII to gypenoside LXXV. Similarly, the enzyme could hydrolyze the glucopyranosyls linked to the 3-O- position of Rb2, Rc, Rd, Rb3, and Rg3. With a larger enzyme reaction Km value, there was a slower enzyme reaction speed; and the larger the enzyme reaction Vmax value, the faster the enzyme reaction speed was. The Km values from small to large were 3.85 mM for Rc, 4.08 mM for Rb1, 8.85 mM for Rb3, 9.09 mM for Rb2, 9.70 mM for Rg3(S), 11.4 mM for Rd and 12.9 mM for F2; and Vmax value from large to small was 23.2 mM/h for Rc, 16.6 mM/h for Rb1, 14.6 mM/h for Rb3, 14.3 mM/h for Rb2, 1.81mM/h for Rg3(S), 1.40 mM/h for Rd, and 0.41 mM/h for F2. According to the Vmax and Km values of the ginsenosidase type III, the hydrolysis speed of these substrates by the enzyme was Rc>Rb1>Rb3>Rb2>Rg3(S)>Rd>F2 in order.

Review of the Molecular Pathogenesis of Osteosarcoma

He, Jin-Peng,Hao, Yun,Wang, Xiao-Lin,Yang, Xiao-Jin,Shao, Jing-Fan,Guo, Feng-Jin,Feng, Jie-Xiong Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.15

Treating the osteosarcoma (OSA) remains a challenge. Current strategies focus on the primary tumor and have limited efficacy for metastatic OSA. A better understanding of the OSA pathogenesis may provide a rational basis for innovative treatment strategies especially for metastases. The aim of this review is to give an overview of the molecular mechanisms of OSA tumorigenesis, OSA cell proliferation, apoptosis, migration, and chemotherapy resistance, and how improved understanding might contribute to designing a better treatment target for OSA.

Mapping Quantitative Trait Loci for Grain Traits Using Near Isogenic Line from a Cross between Oryza minuta and O. sativa

Feng Xue Jin,Le Hung Linh,Kyung Ho Kang,Sang Nag Ahn 한국육종학회 2005 한국육종학회지 Vol.37 No.4

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.

Pyramiding of 2 QTLs, gw8 and gw9, underlying grain weight using nearly isogenic Lines (NILs) in rice

Feng Xue Jin,Xiao Bo Xie,Shi Dong Ji,Hong Guang Ju,Jung Pil Suh,Hung Goo Hwang,Sang Nag Ahn 한국육종학회 2008 한국육종학회 학술발표회 발표요지 Vol.40 No.1

Relationship between Chemical Structures and Functions of Tea Polysaccharides

Feng Jin,Ling-Yan Jia,You-Ying Tu 한국차학회 2015 한국차학회지 Vol.- No.S

The worldwide consumption of tea is second only to water. Thus any health effects of drinking tea could have a significant impact on public health. Although tea has historically been thought to promote good health, research into the possible health benefits of tea is more recent. Tea polysaccharides sources show various important biological activities together with proteins and polynucleotides, such as anti-blood coagulation, anti-radiation, antioxidant, reducing blood sugar levels, hypoglycemic activities, anti-HIV, anti-cancer, cell-cell communication, cell adhesion and molecular recognition in the immune system, which are strongly affected by their chemical structures and chain conformations. In recent years, some tea polysaccharides sources have attracted much attention in the field of biochemistry and pharmacology. Observational studies have repeatedly shown that tea polysaccharides were mostly glycoconjugates in which a protein carries one or more carbohydrate chains covalently associated with a polypeptide backbone, usually some forms of via N- or O-linkages. It is interesting and important to elucidate the relation among chemical structures, chain conformations of tea polysaccharides and their biological activities. However, tea polysaccharides are usually composed of various monosaccharides linked with different glucosidic bonds. Some tea polysaccharides have hyperbranched structures. Moreover, tea polysaccharides often have high molecular weights, and tend to form aggregates in solution that can mask the behavior of individual macromolecules. In consequence, to characterize the chemical structures and chain conformations of polysaccharides is not an easy task. To make clear the chemical structures and chain conformations of tea polysaccharides is important to understand their biological activities. This article attempts to review the current development on structural and conformational characterization of some tea polysaccharides. In this paper, the various aspects of the investigation results of tea polysaccharides chemical structures in the recent decades were summarized. The chemical structures were analyzed by FTIR, NMR (one and two dimensions), CD and AFM, and so on.