Introduction:Cholic acid(CA)is a natural steroid useful in treating chronic bronchitis and cholecystitis.On the other hand,its potential impact on osteoarthritis(OA)is unknown.Objective:Using an in vitro and in vivo o...Introduction:Cholic acid(CA)is a natural steroid useful in treating chronic bronchitis and cholecystitis.On the other hand,its potential impact on osteoarthritis(OA)is unknown.Objective:Using an in vitro and in vivo osteoarthritis model,we sought to assess the chondroprotective properties of CA.Methods:We employed the Cell Counting Kit-8 to measure the impact of CA on chondrocyte activity to assess the toxicity of the cells.Multiple molecular biology experimental techniques were used to investigate potential signaling pathways that CA may use to prevent inflammation and give chondrocytes protection.Furthermore,how CA affects the OA model in Sprague-Dawley(SD)rats was evaluated.Results:CA significantly suppressed the up-regulation of the interleukin-1β(IL-1β),cyclooxygenase-2(COX-2),and matrix metalloproteinase 13(MMP-13)and the downregulation of aggrecan and type II collagen A1(COL2A)in chondrocytes treated tumor necrosis factor-alpha(TNF-α).Differentially expressed genes(DEG)enrichment revealed IL-17,TNF,chemokine,cytokine-cytokine receptor,toll-like receptor,and nucleotide oligomerization domain-like receptor were the primary signaling pathways.The enriched DEGs included CXCL6,CCL20,MMP3,CXCL3,CXCL11,CCL5,CXCL10,MMP9,MMP13,and CXCL2;these DEGs are involved in inflammatory responses and their expression induced by TNF-αwas reversed by CA treatment.CA inhibits p65 nuclear translocation and inhibitory subunit kappa B alpha(IκBα)phosphorylation induced by TNF-α.Furthermore,CA attenuated protein expression of protein kinase RNA-like endoplasmic reticulum kinase(PERK),inositol-requiring transmembrane kinase/endoribonuclease 1α(IRE1α),glucose regulatory protein 78(GRP78),and sirtuin 1(SIRT1),and down-regulation of phosphorylation of AMP-activated protein kinase-α(p-AMPKα)in TNF-α-treated chondrocytes.Conclusions:CA significantly ameliorated cartilage degradation in the OA rat model.CA alleviated the inflammatory response through the nuclear factor kappa B/PERK/SIRT1 axis and ameliorated cartilage degradation.展开更多
Objective:To investigate the pharmacological action and mechanism of cholic acid derivatives in traditional Chinese medicine(TCM)based on the regulation of gene expression.Methods:Genome-wide gene expression profiles ...Objective:To investigate the pharmacological action and mechanism of cholic acid derivatives in traditional Chinese medicine(TCM)based on the regulation of gene expression.Methods:Genome-wide gene expression profiles of Michigan Cancer Foundation-7(MCF-7)cells treated with or without 4 cholic acid derivatives were detected by gene chip technology.Similarities in upregulated and downregulated genes were analyzed using the Connectivity Map(CMap)database.The affinity between cholic acid derivatives and the potential target was confirmed by molecular docking.The cholic acid derivative-regulated pathway enrichment analysis was performed by the STRING database,and the potential pathway was confirmed by in vitro experiments on MD Anderson-Metastatic Breast-231(MDA-MB-231)cells.Results:Compared with the reference genome in the CMap database,the gene expression profiles of cholic acid derivatives were similar to those of antipsychotic,anticancer,anti-inflammatory,and antiinfective drugs.Among them,4 derivatives were associated with antianxiety drugs,and molecular docking results showed that these compounds may act by binding to the ligand-binding site of gammaaminobutyric acid(GABA)receptors.Moreover,the cytoskeletal pathway is one of the pathways enriched in the derivatives.Of them,ursodeoxycholic acid showed significant inhibitory activity on the cytoskeleton formation of MDA-MB-231 cells.Conclusion:The gene expression detection method,combined with CMap and pathway enrichment analysis,could be used to study the mechanism of the active ingredients of TCM.In addition,our research showed that cholic acid derivatives have a potential affinity for membrane receptors,where they can exert anxiolytic activity by modulating opioid receptor,GABA receptor,and dopamine receptor.Moreover,ursodeoxycholic and chenodeoxycholic acid inhibit cytoskeleton formation,probably by acting on membrane proteins to activate the corresponding cytoskeletal pathways.展开更多
This study examined the effect of cholic acid （CA） on cultured cardiac myoeytes （CMs） from neonatal rats with an attempt to explore the possible mechanism of sudden fetal death in intra- hepatic cholestasis of pre...This study examined the effect of cholic acid （CA） on cultured cardiac myoeytes （CMs） from neonatal rats with an attempt to explore the possible mechanism of sudden fetal death in intra- hepatic cholestasis of pregnancy （ICP）. Inverted microscopy was performed to detect the impact of CA on the beating rates of rat CMs. MTT method was used to study the effect of CA on the viability of CMs. CMs cultured in vitro were incubated with 10 ~maol/L Ca2＋-sensitive fluorescence indicator fluo-3/AM. The fluorescence signals of free calcium induced by CA were measured under a laser scanning confocal microscope. The results showed that CA decreased the beating rates of the CMs in a dose-dependent manner. CA could suppress the activities of CMs in a time- and dose-dependent manner. CA increased the concentration of intracellular free calcium in a dose-dependent manner. Our study suggested that CA could inhibit the activity of CMs by causing calcium overload, thereby leading to the sudden fetal death in ICP.展开更多
A series of hepatic targeting drugs, 5-Fu-cholic acid conjugate T1-T5, were synthesized. 5-Fu and cholic acid was selected as starting material, after N-hydroxymethylation, condensation, hydrogenolysis to obtain carbo...A series of hepatic targeting drugs, 5-Fu-cholic acid conjugate T1-T5, were synthesized. 5-Fu and cholic acid was selected as starting material, after N-hydroxymethylation, condensation, hydrogenolysis to obtain carboxylated 5-Fu 5a-e. Carboxylated 5-Fu 5a-e were condensated with intermediate 3-hydroxyethyl cholic acid benzyl ester 6 to get 7a-e, 7a-e were deprotected to get T1- T5.展开更多
Based on cryogenic FT-IR spectroscopic studies of hydrogen bonds in cholic acid, two-dimensional FT-IR spectroscopy was applied to enhance our understanding of the hydrogen bonds of cholic acid. Fine spectral structu...Based on cryogenic FT-IR spectroscopic studies of hydrogen bonds in cholic acid, two-dimensional FT-IR spectroscopy was applied to enhance our understanding of the hydrogen bonds of cholic acid. Fine spectral structures were revealed by asynchronous 2D FT-IR spectra. The co-relationship among various bands was discussed according to the synchronous 2D FT-IR spectrum.展开更多
2＇-methacryloxy-3α, 7α, I2α- trimethacryloyl cholic acid ethyl ester （CAGE4MA） has been prepared from cholic acid. Photo-polymeric resins were prepared from CAGE4MA. 2,2-bis[4-（2-hydroxy-3-methacrylyloxypropoxy...2＇-methacryloxy-3α, 7α, I2α- trimethacryloyl cholic acid ethyl ester （CAGE4MA） has been prepared from cholic acid. Photo-polymeric resins were prepared from CAGE4MA. 2,2-bis[4-（2-hydroxy-3-methacrylyloxypropoxy）phenyllpropane （bis-GMA） was used for comparison, triethyleneglycol dimethacrylate （TEGDMA） was used as diluent. The polymerization was initiated by camphoroquinone （CQ）/N, N-dimethylaminoethyl methacrylate （DMAEMA） system. The conversion of CAGE4MA was 39% when the reaction time is 60s, which is lower than bis-GMA and TEGDMA. The swelling value of CAGE4MA resin was 0.41% in distilled water, which is much lower than those of bis-GMA resin （2.04%） and TEGDMA resin （4.77%） under the same conditions. Copolymers from CAGE4MA and TEGDMA have been prepared. With the increase of TEGDMA in mixture, the degree of conversion of CA GE4MA and swelling value increased. The swelling values of photocured resins in 0.1mol/L HCl were also measured.展开更多
A new copolymer was synthesized by free radical polymerization in solution from methyl 3α-methylacryloyl-7α, 12α-dihydroxy-5β-cholan-24-oate (MACAME) and maleic anhydride (MAN). The copolymer was characterized by ...A new copolymer was synthesized by free radical polymerization in solution from methyl 3α-methylacryloyl-7α, 12α-dihydroxy-5β-cholan-24-oate (MACAME) and maleic anhydride (MAN). The copolymer was characterized by FT-IR and functional group analysis. The reactivity ratios of the two monomers were estimated [r_1 = 11.6 (MACAME), r_2 = 0.01(MAN)] by conducting a series of copolymerizations with a variety of monomer feed compositions and analyzing thecopolymer composition. Thermogravimetric and differential scanning calorimetric analyses of the samples indicate that thecopolymer possesses good thermal stability. The temperature at which the copolymer samples experienced a 10% weight loss(T_(WL)) is over 287℃, and the T_g ranged from 174 to 185℃ for the copolymers.展开更多
A novel type of chiral molecular clefts consisting of a rigid deoxycholic acid methyl ester backbone and chiral unsymmetrically disubstituted urea side chain have been designed and synthesized. All these new receptor...A novel type of chiral molecular clefts consisting of a rigid deoxycholic acid methyl ester backbone and chiral unsymmetrically disubstituted urea side chain have been designed and synthesized. All these new receptors 3a^c and the corresponding key intermediates 1a^c and 2a^c are new compounds, their structures were confirmed by 1HNMR, IR, MS spectra and elemental analysis. These molecular clefts showed binding ability for halide anions.展开更多
The aim of the study was to describe the binding of cholic acid by hemicellulose and pectin of yard-long bean at gastrointestinal system （in vitro）, through variation of acidity （pH 3, 5 and 7） and boiling time （...The aim of the study was to describe the binding of cholic acid by hemicellulose and pectin of yard-long bean at gastrointestinal system （in vitro）, through variation of acidity （pH 3, 5 and 7） and boiling time （raw/0, 5, 20 and 35 minutes） of yard-long bean. Two-way Anova （α= 5%） and functional groups analysis by infrared spectrophotometer were applied for the binding description. The results of the study showed： （1） The highest binding percentage of cholic acid by dietary fiber of yard-long bean at pH 3-raw treatment （76.603%）; （2） Cholic acid binding via C = O/ester or acid of hemicellulose, C-O-C/cyclic ether of pectin, while C = O/ester or acid of oectin through iron.展开更多
A simpe electrochemical sensor for detection of cholic acid （CA） was designed by modifying phosphomolybdate （PMol2） doped polypyrrole （PPy） film on glassy carbon electrode （PMo12-PPy/GCE）. The electrochemical ...A simpe electrochemical sensor for detection of cholic acid （CA） was designed by modifying phosphomolybdate （PMol2） doped polypyrrole （PPy） film on glassy carbon electrode （PMo12-PPy/GCE）. The electrochemical behavior of CA on PMo12-PPy/GCE was investigated by cyclic voltammetry and 0.5 order differential voltammetry. The results indicated that CA had high inhibitory activity toward the peak currents of PMo12-PPy/GCE. The reduction peak currents were linearly related to the logarithmic value of the concentration of CA from 1.0 × 10^- 7 to 1.0 × 10^-3 mol/L with a low detection limit of 1.0 × 10^- 8 mol/L. The developed sensor exhibited excellent sensitivity, selectivity and stability for detection of CA, and it could be successfully applied to detect the level of CA in the urine samples. Moreover, the response mechanism of CA on the PMo12-PPy/GCE was discussed in detail.展开更多
New steroid dimer,ethylene bridged bis-carbamate(3) was synthesized from cholic acid in few steps. Complexes of 3 with lanthanum(Ⅲ) and calcium(Ⅱ) nitrates were prepared in reaction of 3 and appropriate metal salts....New steroid dimer,ethylene bridged bis-carbamate(3) was synthesized from cholic acid in few steps. Complexes of 3 with lanthanum(Ⅲ) and calcium(Ⅱ) nitrates were prepared in reaction of 3 and appropriate metal salts. They were characterized by spectral data(Infrared(IR) ,ultraviolet-visible(UV/Vis) ,nuclear magnetic resonance(NMR) spectroscopy and fast-atom bombardment(FAB) ,electrospray(ESI) and matrix-assisted laser desorption/ionization mass spectrometry(MALDI-MS)) and elemental analysis. The similarity in complexing behavior of steroidal dimer toward calcium and lanthanum ions was observed.展开更多
基金This work was financially supported by the Open Fund for Hubei Provincial Key Laboratory of Occurrence and Intervention of Rheumatic Diseases(PT022311).
文摘Introduction:Cholic acid(CA)is a natural steroid useful in treating chronic bronchitis and cholecystitis.On the other hand,its potential impact on osteoarthritis(OA)is unknown.Objective:Using an in vitro and in vivo osteoarthritis model,we sought to assess the chondroprotective properties of CA.Methods:We employed the Cell Counting Kit-8 to measure the impact of CA on chondrocyte activity to assess the toxicity of the cells.Multiple molecular biology experimental techniques were used to investigate potential signaling pathways that CA may use to prevent inflammation and give chondrocytes protection.Furthermore,how CA affects the OA model in Sprague-Dawley(SD)rats was evaluated.Results:CA significantly suppressed the up-regulation of the interleukin-1β(IL-1β),cyclooxygenase-2(COX-2),and matrix metalloproteinase 13(MMP-13)and the downregulation of aggrecan and type II collagen A1(COL2A)in chondrocytes treated tumor necrosis factor-alpha(TNF-α).Differentially expressed genes(DEG)enrichment revealed IL-17,TNF,chemokine,cytokine-cytokine receptor,toll-like receptor,and nucleotide oligomerization domain-like receptor were the primary signaling pathways.The enriched DEGs included CXCL6,CCL20,MMP3,CXCL3,CXCL11,CCL5,CXCL10,MMP9,MMP13,and CXCL2;these DEGs are involved in inflammatory responses and their expression induced by TNF-αwas reversed by CA treatment.CA inhibits p65 nuclear translocation and inhibitory subunit kappa B alpha(IκBα)phosphorylation induced by TNF-α.Furthermore,CA attenuated protein expression of protein kinase RNA-like endoplasmic reticulum kinase(PERK),inositol-requiring transmembrane kinase/endoribonuclease 1α(IRE1α),glucose regulatory protein 78(GRP78),and sirtuin 1(SIRT1),and down-regulation of phosphorylation of AMP-activated protein kinase-α(p-AMPKα)in TNF-α-treated chondrocytes.Conclusions:CA significantly ameliorated cartilage degradation in the OA rat model.CA alleviated the inflammatory response through the nuclear factor kappa B/PERK/SIRT1 axis and ameliorated cartilage degradation.
基金supported by the National Natural Science Foundation of China(22067016).
文摘Objective:To investigate the pharmacological action and mechanism of cholic acid derivatives in traditional Chinese medicine(TCM)based on the regulation of gene expression.Methods:Genome-wide gene expression profiles of Michigan Cancer Foundation-7(MCF-7)cells treated with or without 4 cholic acid derivatives were detected by gene chip technology.Similarities in upregulated and downregulated genes were analyzed using the Connectivity Map(CMap)database.The affinity between cholic acid derivatives and the potential target was confirmed by molecular docking.The cholic acid derivative-regulated pathway enrichment analysis was performed by the STRING database,and the potential pathway was confirmed by in vitro experiments on MD Anderson-Metastatic Breast-231(MDA-MB-231)cells.Results:Compared with the reference genome in the CMap database,the gene expression profiles of cholic acid derivatives were similar to those of antipsychotic,anticancer,anti-inflammatory,and antiinfective drugs.Among them,4 derivatives were associated with antianxiety drugs,and molecular docking results showed that these compounds may act by binding to the ligand-binding site of gammaaminobutyric acid(GABA)receptors.Moreover,the cytoskeletal pathway is one of the pathways enriched in the derivatives.Of them,ursodeoxycholic acid showed significant inhibitory activity on the cytoskeleton formation of MDA-MB-231 cells.Conclusion:The gene expression detection method,combined with CMap and pathway enrichment analysis,could be used to study the mechanism of the active ingredients of TCM.In addition,our research showed that cholic acid derivatives have a potential affinity for membrane receptors,where they can exert anxiolytic activity by modulating opioid receptor,GABA receptor,and dopamine receptor.Moreover,ursodeoxycholic and chenodeoxycholic acid inhibit cytoskeleton formation,probably by acting on membrane proteins to activate the corresponding cytoskeletal pathways.
基金supported by a grant from Union Hospital,Tongji Medical College,Huazhong University of Science and Technology(No.Union-Grant 02.03.2012-03)
文摘This study examined the effect of cholic acid （CA） on cultured cardiac myoeytes （CMs） from neonatal rats with an attempt to explore the possible mechanism of sudden fetal death in intra- hepatic cholestasis of pregnancy （ICP）. Inverted microscopy was performed to detect the impact of CA on the beating rates of rat CMs. MTT method was used to study the effect of CA on the viability of CMs. CMs cultured in vitro were incubated with 10 ~maol/L Ca2＋-sensitive fluorescence indicator fluo-3/AM. The fluorescence signals of free calcium induced by CA were measured under a laser scanning confocal microscope. The results showed that CA decreased the beating rates of the CMs in a dose-dependent manner. CA could suppress the activities of CMs in a time- and dose-dependent manner. CA increased the concentration of intracellular free calcium in a dose-dependent manner. Our study suggested that CA could inhibit the activity of CMs by causing calcium overload, thereby leading to the sudden fetal death in ICP.
基金supported by the National Natural Science Foundation of China(No.30672537)Special Research Fund for Dr.discipline Sites of Colleges and Universities(No.20050610085).
文摘A series of hepatic targeting drugs, 5-Fu-cholic acid conjugate T1-T5, were synthesized. 5-Fu and cholic acid was selected as starting material, after N-hydroxymethylation, condensation, hydrogenolysis to obtain carboxylated 5-Fu 5a-e. Carboxylated 5-Fu 5a-e were condensated with intermediate 3-hydroxyethyl cholic acid benzyl ester 6 to get 7a-e, 7a-e were deprotected to get T1- T5.
基金The Project was supported by State Key Project of Basic Research MOST G1998061307 the National Natural Science Foundation of China (NSFC+8 种基金 grant No. 59733060 59873030 59953001 59903008 29671002 39730160 20023005 29901002) and Major Proj
文摘Based on cryogenic FT-IR spectroscopic studies of hydrogen bonds in cholic acid, two-dimensional FT-IR spectroscopy was applied to enhance our understanding of the hydrogen bonds of cholic acid. Fine spectral structures were revealed by asynchronous 2D FT-IR spectra. The co-relationship among various bands was discussed according to the synchronous 2D FT-IR spectrum.
文摘2＇-methacryloxy-3α, 7α, I2α- trimethacryloyl cholic acid ethyl ester （CAGE4MA） has been prepared from cholic acid. Photo-polymeric resins were prepared from CAGE4MA. 2,2-bis[4-（2-hydroxy-3-methacrylyloxypropoxy）phenyllpropane （bis-GMA） was used for comparison, triethyleneglycol dimethacrylate （TEGDMA） was used as diluent. The polymerization was initiated by camphoroquinone （CQ）/N, N-dimethylaminoethyl methacrylate （DMAEMA） system. The conversion of CAGE4MA was 39% when the reaction time is 60s, which is lower than bis-GMA and TEGDMA. The swelling value of CAGE4MA resin was 0.41% in distilled water, which is much lower than those of bis-GMA resin （2.04%） and TEGDMA resin （4.77%） under the same conditions. Copolymers from CAGE4MA and TEGDMA have been prepared. With the increase of TEGDMA in mixture, the degree of conversion of CA GE4MA and swelling value increased. The swelling values of photocured resins in 0.1mol/L HCl were also measured.
基金NSERC of Canada and Nankai University for financial support. H. Li thanks the National Natural Science Foundation of China for a travel award in support of the collaborative research program (No. 20074016).
文摘A new copolymer was synthesized by free radical polymerization in solution from methyl 3α-methylacryloyl-7α, 12α-dihydroxy-5β-cholan-24-oate (MACAME) and maleic anhydride (MAN). The copolymer was characterized by FT-IR and functional group analysis. The reactivity ratios of the two monomers were estimated [r_1 = 11.6 (MACAME), r_2 = 0.01(MAN)] by conducting a series of copolymerizations with a variety of monomer feed compositions and analyzing thecopolymer composition. Thermogravimetric and differential scanning calorimetric analyses of the samples indicate that thecopolymer possesses good thermal stability. The temperature at which the copolymer samples experienced a 10% weight loss(T_(WL)) is over 287℃, and the T_g ranged from 174 to 185℃ for the copolymers.
基金the National Natural Science Foundation of China for the financial support(Project No.:20072026).
文摘A novel type of chiral molecular clefts consisting of a rigid deoxycholic acid methyl ester backbone and chiral unsymmetrically disubstituted urea side chain have been designed and synthesized. All these new receptors 3a^c and the corresponding key intermediates 1a^c and 2a^c are new compounds, their structures were confirmed by 1HNMR, IR, MS spectra and elemental analysis. These molecular clefts showed binding ability for halide anions.
文摘The aim of the study was to describe the binding of cholic acid by hemicellulose and pectin of yard-long bean at gastrointestinal system （in vitro）, through variation of acidity （pH 3, 5 and 7） and boiling time （raw/0, 5, 20 and 35 minutes） of yard-long bean. Two-way Anova （α= 5%） and functional groups analysis by infrared spectrophotometer were applied for the binding description. The results of the study showed： （1） The highest binding percentage of cholic acid by dietary fiber of yard-long bean at pH 3-raw treatment （76.603%）; （2） Cholic acid binding via C = O/ester or acid of hemicellulose, C-O-C/cyclic ether of pectin, while C = O/ester or acid of oectin through iron.
基金This work was supported by the Natural Science Foundation of Shanxi Province, China （No. 201601D202008） and the Joint Funds of the National Natural Science Foundation of China （No. U 1510103）.
文摘A simpe electrochemical sensor for detection of cholic acid （CA） was designed by modifying phosphomolybdate （PMol2） doped polypyrrole （PPy） film on glassy carbon electrode （PMo12-PPy/GCE）. The electrochemical behavior of CA on PMo12-PPy/GCE was investigated by cyclic voltammetry and 0.5 order differential voltammetry. The results indicated that CA had high inhibitory activity toward the peak currents of PMo12-PPy/GCE. The reduction peak currents were linearly related to the logarithmic value of the concentration of CA from 1.0 × 10^- 7 to 1.0 × 10^-3 mol/L with a low detection limit of 1.0 × 10^- 8 mol/L. The developed sensor exhibited excellent sensitivity, selectivity and stability for detection of CA, and it could be successfully applied to detect the level of CA in the urine samples. Moreover, the response mechanism of CA on the PMo12-PPy/GCE was discussed in detail.
基金Project supported by the Polish Ministry of Science and Higher Education (NN204 166 836)
文摘New steroid dimer,ethylene bridged bis-carbamate(3) was synthesized from cholic acid in few steps. Complexes of 3 with lanthanum(Ⅲ) and calcium(Ⅱ) nitrates were prepared in reaction of 3 and appropriate metal salts. They were characterized by spectral data(Infrared(IR) ,ultraviolet-visible(UV/Vis) ,nuclear magnetic resonance(NMR) spectroscopy and fast-atom bombardment(FAB) ,electrospray(ESI) and matrix-assisted laser desorption/ionization mass spectrometry(MALDI-MS)) and elemental analysis. The similarity in complexing behavior of steroidal dimer toward calcium and lanthanum ions was observed.
