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Da-Hua Shi,Jun-Hua Wu,Zhi-Qiang Yan,Li-Na Zhang,Yu-Rong Wang,Chun-Ping Jiang 대한약학회 2012 Archives of Pharmacal Research Vol.35 No.9
To find the multi-target-directed compounds for the treatment of Alzheimer’s disease (AD), we synthesized 7-(4-(diethylamino)butoxy)-5-hydroxy-3-(4-hydroxyphenyl)-4H-chromen-4-one, a novel 7-O-modified genistein derivative (GS-14), and investigated its acetylcholinesterase (AChE) inhibitory effect, estrogenic activity and neuroprotective effect. GS-14 acted as a selective AChE inhibitor in vitro, with an IC50 value of 0.17 μM and showed no inhibition activity against butyrylcholinesterase (BuChE). The Lineweaver–Burk plot revealed that GS-14 was a non-competitive AChE inhibitor with a Ki value of 0.23 μM and the molecular docking model indicated that GS-14 interacted with the peripheral anionic site (PAS) of AChE. The MCF-7 proliferation assay demonstrated that GS-14 possessed estrogenic activity and GS-14 exhibited a high specificity for estrogen receptor β (ERβ) with a dissociation constant (Ki) of 2.86 nM compared with that of 1.01 μM for estrogen receptor α (ERα) in the molecular docking study. GS-14 also possessed a neuroprotective effect and showed the best protective effect against the β-amyloid protein-induced injury on SH-SY5Y cells at a concentration of 1 nM. Considering its AChEinhibition activity, estrogenic activity and neuroprotective effect, GS-14 may be a potential multi-target agent for the treatment of AD.
鄭大華(Zheng Da-Hua) 동북아시아문화학회 2003 동북아 문화연구 Vol.1 No.5
The statecraft ideology beame revived in order to overcome an in-and-outside-the-country crisis situation since Daoguang(道光) and Xianfeng(咸豊) period of Qing(?). Bao Shishen is one of the typical persons who brought about the trends of statecraft at that time. However, there have been few previous studies on him. This paper discusses Bao Shishen"s trends of statecraft during Daoguang and Xianfeng period of Qing. The first half of this paper describes how the academic traditions of Daoguang and Xianfeng period changed and how pragmatism came about. The second half describes Bao Shishen"s thought and the Opium War (a war against Great Britain for prohibition of drug) during Daoguang and Xianfeng period. And this paper finally concludes the historical implications of Bao Shishen"s trends of statecraft. It is claimed in this paper that Bao Shishen must be re-appreciated as a historic figure who lead the changes during that period because his claims for social reform were earlier and deeper in a certain area than Gong Zi-zhen(?自珍)and Wei Yuan(魏源).
Xing-Xi Gao,Jun-Hua Wu,Da-Hua Shi,Yun-Xi Chen,Jiang-Tao Cui,Yu-Rong Wang,Chun-Ping Jiang 대한약학회 2012 Archives of Pharmacal Research Vol.35 No.8
The aim of this study was to investigate the effects of tectorigenin on chemically induced liver fibrosis in rats. Liver fibrosis was induced in rats with carbon tetrachloride, a diet high in fat, cholesterol and alcohol in the drinking water. Our results indicate that tectorigenin treatment significantly inhibited the increases in the activities of alanine aminotransferase (ALT),aspartate aminotransferase (AST) and the increases in the serum levels of hyaluronate (HA), laminin (LN) and procollagen III N-terminal peptide (PIIIP); tectorigenin treatment also significantly inhibited the increases in the amount of collagen in the livers of the fibrogenic rats. Chemically induced liver fibrosis caused a drop in the serum albumin concentration and a decrease in the ratio of albumin to globulin (A/G). Tectorigenin caused a remarkable increase at a dose of 30 mg/kg, but only a slight increase at the lower doses. Tectorigenin was also able to inhibit the increase in the liver lipid peroxidation (LPO), as well as the decrease in the activities of liver superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), caused by liver fibrosis. In addition, we present a related metabolic profile determined, using a 1H NMR spectroscopy and multivariate pattern recognition techniques. The results were consistent with the pathological examination, liver function analysis and liver fibrosis marker analysis. Furthermore, tectorigenin does not cause acute toxicity.
Da-Hong Li,Jia Guo,Wen Bin,Nan Zhao,Kai-bo Wang,Jian-yong Li,Zhan-Lin Li,Hui-Ming Hua 대한약학회 2016 Archives of Pharmacal Research Vol.39 No.7
Two novel rare chloro-containing benzylisoquinolinealkaloids, thalfoliolosumines A (1) and B (2),along with eight known isoquinoline alkaloids (3–10) wereisolated from the whole plant of Thalictrum foliolosum. The structures of these compounds were elucidated byspectral analyses, including 1D and 2D NMR (COSY,HSQC, HMBC and NOESY) experiments. The antiproliferativeeffects of all the isolated compounds were evaluatedby MTT method against MCF-7, PC-3, and U937cells, and trypan blue method against HL-60 cells. Newcompounds 1 and 2 exhibited moderate in vitro antiproliferativeactivity against MCF-7, PC-3, and HL-60 cells,and good inhibitory effects against U937 cells with IC50values of 7.50 and 6.97 μM, respectively. Compounds 7and 10 showed the strongest in vitro antiproliferative withIC50 values of 0.93 and 1.69 lM against HL-60 cell line. The antioxidant properties were also measured, bisbenzyltetrahydroisoquinolinealkaloids 3–6 showed the strongestantioxidant activities in ABTS assay.
Xanthones from Garcinia paucinervis with in vitro anti-proliferative activity against HL-60 cells
Da-Hong Li,Chen-Xi Li,Cui-Cui Jia,Ya-Ting Sun,Chun-Mei Xue,Jiao Bai,Hui-Ming Hua,Xiao-Qiu Liu,Zhan-Lin Li 대한약학회 2016 Archives of Pharmacal Research Vol.39 No.2
Three new xanthones, paucinervins H–J (1–3), as well as eleven known compounds (4–14), were isolated from the leaves of Garcinia paucinervis. The structures of the new compounds (1–3) were elucidated by 1D, 2D NMR spectra and HR ESIMS. In vitro antiproliferative activity against human promyelocytic leukemia HL-60 cells was tested, among which, compounds 2, 5, 6 and 7 exhibited strong growth inhibitory effects with GI50 values ranging from 1.30 to 9.08 lM, respectively. Preliminary SARs were also discussed.
Anti-Inflammatory Activity of Sulfur-Containing Compounds from Garlic
Da Yeon Lee,Hua Li,Hyo Jin Lim,이화진,전라옥,류재하 한국식품영양과학회 2012 Journal of medicinal food Vol.15 No.11
We identified four anti-inflammatory sulfur-containing compounds from garlic, and their chemical structures were identified as Z- and E-ajoene and oxidized sulfonyl derivatives of ajoene. The sulfur compounds inhibited the production of nitric oxide (NO) and prostaglandin E2 (PGE2) and the expression of the pro-inflammatory cytokines tumor necrosis factor-α, interleukin-1β, and interleukin-6 in lipopolysaccharide (LPS)-activated macrophages. Western blotting and reverse transcription–polymerase chain reaction analysis demonstrated that these sulfur compounds attenuated the LPS-induced expression of the inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) proteins and mRNA. Moreover, these sulfur-containing compounds suppressed the nuclear factor-κB (NF-κB) transcriptional activity and the degradation of inhibitory-κBα in LPS-activated macrophages. Furthermore, we observed that they markedly inhibited the LPS-induced phosphorylations of p38 mitogen-activated protein kinases and extracellular signal-regulated kinases (ERK) at 20 μM. These data demonstrate that the sulfur compounds from garlic, (Z, E)-ajoene and their sulfonyl analogs, can suppress the LPS-induced production of NO/PGE2 and the expression of iNOS/COX-2 genes by inhibiting the NF-κB activation and the phosphorylations of p38 and ERK. Taken together, these data show that Z- and E-ajoene and their sulfonyl analogs from garlic might have anti-inflammatory therapeutic potential.
Da Zhou,Yuan-Wen Chen,Ze-Hua Zhao,Rui-Xu Yang,Feng-Zhi Xin,Xiao-Lin Liu,Qin Pan,Huiping Zhou,Jian-Gao Fan 생화학분자생물학회 2018 Experimental and molecular medicine Vol.50 No.-
Glucagon-like peptide-1 (GLP-1) has a broad spectrum of biological activity by regulating metabolic processes via both the direct activation of the class B family of G protein-coupled receptors and indirect nonreceptor-mediated pathways. GLP-1 receptor (GLP-1R) agonists have significant therapeutic effects on non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) in animal models. However, clinical studies indicated that GLP-1 treatment had little effect on hepatic steatosis in some NAFLD patients, suggesting that GLP-1 resistance may occur in these patients. It is wellknown that the gut metabolite sodium butyrate (NaB) could promote GLP-1 secretion from intestinal L cells. However, it is unclear whether NaB improves hepatic GLP-1 responsiveness in NAFLD. In the current study, we showed that the serum GLP-1 levels of NAFLD patients were similar to those of normal controls, but hepatic GLP-1R expression was significantly downregulated in NAFLD patients. Similarly, in the NAFLD mouse model, mice fed with a high-fat diet showed reduced hepatic GLP-1R expression, which was reversed by NaB treatment and accompanied by markedly alleviated liver steatosis. In addition, NaB treatment also upregulated the hepatic p-AMPK/p-ACC and insulin receptor/ insulin receptor substrate-1 expression levels. Furthermore, NaB-enhanced GLP-1R expression in HepG2 cells by inhibiting histone deacetylase-2 independent of GPR43/GPR109a. These results indicate that NaB is able to prevent the progression of NAFL to NASH via promoting hepatic GLP-1R expression. NaB is a GLP-1 sensitizer and represents a potential therapeutic adjuvant to prevent NAFL progression to NASH.
( Yao Da Lei ),( Zhang Chang Hao ),( Li Ren ),( Luo Jie ),( Jin Mei ),( Piao Jin Hua ),( Zheng Ming Shan ),( Cui Jiong Mo ),( Son Jong Keun ),( Li Gao ) 영남대학교 약품개발연구소 2015 영남대학교 약품개발연구소 연구업적집 Vol.25 No.-
The present study was designed to isolate and characterize novel chemical constituents of the stem bark of Juglans mandshurica Maxim. (Juglandaceae).The chemical constituents were isolated and purified by various chromatographic techniques. The structures of the compounds were elucidated on the basis of spectral data (1D and 2D NMR, HR-ESI-MS, CD, UV, and IR) and by the comparisons of spectroscopic data with the reported values in the literatures. Two long chain polyunsaturated fatty acids (1 and 2) were obtained and identified as (S)-(8E, 10E)-12-hydroxy-7-oxo-8, 10-octadecadienoic acid (1) and (S)-(8E, 10E)-12-hydroxy-7-oxo-8,10-octadecadienoic acid methyl ester (2). To the best of our knowledge, this is the first report on the isolation and structural elucidation of the two new conjugated ketonic fatty acids from this genus.