AIM： To investigate the effect of 5, 7-dihydroxy-8- nitrochrysin （NOChR） on apoptosis of human gastric carcinoma SGC-7901 cell line.METHODS： SGC-7901 cells were cultured in vitro and the inhibitory effect of NOChR...AIM： To investigate the effect of 5, 7-dihydroxy-8- nitrochrysin （NOChR） on apoptosis of human gastric carcinoma SGC-7901 cell line.METHODS： SGC-7901 cells were cultured in vitro and the inhibitory effect of NOChR on proliferation of SGC-7901 cells was measured by using an Ml-r assay. NOChR-induced apoptosis rate of SGC-7901 cells was detected using flow cytometry （FCM） with PI staining. DNA ladder bands were observed by DNA agarose gel electrophoresis. The influence of NOChR on the proxisome proliferator-activated receptor-γ （PPARγ）, Bcl-2 and Bax protein expression of SGC-7901 cells was analyzed by Western blot.RESULTS： MIF assay showed that NOChR markedly inhibited proliferation of SGC-7901 cells in a dose- dependent manner, and when ICso was 4.14 μmol/L, the potency of NOChR was 10 times than that of lead compound, chrysin （ChR, IC50 was 40.56 μmol/L）, and was similar to 5-fluorouracil （5-FU, IC50 was 4.51 μmol/L）. FCM with propidium iodide （PI） staining demonstrated that the apoptosis rates of SGC-7901 cells treated with 1.25, 5.00 and 20.00 μmol/L NOChR for 48 h were 9.8% 4- 0.2%, 36.8% 4- 1.9% and 45.5% 4- 3.5%, respectively, and were significantly higher when treated with 5.00 and 20.00 μmol/L NOChR than that with 20.00 μmol/L ChR （12.9% 4- 1.5%）. DNA agarose gel electrophoresis showed that treatment of SGC-7901 cells with 20.00 μmol/L NOChR for 48 h resulted in typical DNA ladder bands of DNA of SGC-7901 cells, which could be eliminated by treating with 10.00 μmol/L GW9662, a blocker of PPARy. Western blot analysis revealed that after 24 h of treatment with 20.00 μmol/L NOChR, PPARgamma and Bax protein expression of SGC-7901 cells increased but Bcl-2 expression decreased; however, pre-incubation with 10.00 μmol/L GW9662 could efficiently antagonize and weaken the regulatory effect of 20.00 μmol/L NOChR on Bax and Bcl-2 protein expression of SGC-7901 cells. CONCLUSION： NOChR induces apoptosis of SGO7901 cell lines by activating PPARy and decreasing ratio of Bcl-2 to Bax.展开更多
AIM： To investigate the effect of 5-allyl-7-gen-difluoromethylenechrysin （ADFMChR） on apoptosis of human liver carcinoma HepG2 cell line and the molecular mechanisms involved.METHODS： HepG2 cells and L-02 cells we...AIM： To investigate the effect of 5-allyl-7-gen-difluoromethylenechrysin （ADFMChR） on apoptosis of human liver carcinoma HepG2 cell line and the molecular mechanisms involved.METHODS： HepG2 cells and L-02 cells were cultured in vitro and the inhibitory effect of ADFMChR on their proliferation was measured by MTT assay. The apoptosis of HepG2 cells was determined by flow cytometry （FCM） using propidium iodide （PI） fluorescence staining. DNA ladder bands were observed by DNA agarose gel electrophoresis. The influence of ADFMChR on the proxisome proliferator-activated receptor γ （PPARγ）, NF-κB, Bcl-2 and Bax protein expression of HepG2 cells were analyzed by Western blotting.RESULTS： MTT assay showed that ADFMChR significantly inhibited proliferation of HepG2 cells in a dose- dependent manner, with little effect on growth of L-02 cells, and when ICs0 was measured as 8.45 μmol/L and 191.55 μmol/L respectively, the potency of ADFMChR to HepG2 cells, was found to be similar to 5-fluorouracil （5-FU, ICso was 9.27 μmol/L）. The selective index of ADFMChR cytotoxicity to HepG2 cells was 22.67 （191.55/8.45）, higher than 5-FU （SI was 7.05 （65.37/9.27）. FCM with PI staining demonstrated that the apoptosis rates of HepG2 cells treated with 3.0, 10.0 and 30.0 μmol/L ADFMChR for 48 h were 5.79%, 9.29% and 37.8%, respectively, and were significantly higher when treated with 30.0 μmol/L ADFMChR than when treated with 30.0 μmol/L ChR （16.0%） （P 〈 0.05） and were similar to those obtained with 30.0 μmol/L 5-FU（41.0%）. DNA agarose gel electrophoresis showed that treatment of HepG2 cells with 10.0 μmol/L ADFMChR for 48 h and 72 h resulted in typical DNA ladders which could be reversed by 10.00 pmol/1 GW9662, a blocker of PPARy. Western blotting analysis revealed that aEer 24 h of treatment with 3.0, 10.0, 30.0 μmol/L ADFMChR, PPARy and Bax protein expression in HepG2 cells increased but Bcl-2 and NF-κB expression decreased; however, pre-incubation with 10.0 μmol/L GW9662 could efficiently antagonize and weaken the regulatory effect of 3.0, 30.0 μmol/L ADFMChR on PPARy and NF-KB protein expression in HepG2 cells.CONCLUSION： ADFMChR induces apoptosis of HepG2 cell lines by activating PPARγ, inhibiting protein expression of Bcl-2 and NF-κB, and increasing Bax expression.展开更多
Chrysin(1) and tectochrysin(2) were respectively synthesized in four steps from 1,3,5-tribromobenzene in an overall yield of 46.8% and that of 37.0% with the key step being the Bu_4NBr catalyzed hydrolysis of 1-phenyl...Chrysin(1) and tectochrysin(2) were respectively synthesized in four steps from 1,3,5-tribromobenzene in an overall yield of 46.8% and that of 37.0% with the key step being the Bu_4NBr catalyzed hydrolysis of 1-phenyl-3-(2′,4′,6′-trimethoxyphenyl)-1, 3-propanedione (11) under different conditions.展开更多
AIM:To investigate whether the apoptotic activities of 8-bromo-7-methoxychrysin(BrMC) involve reactive oxygen species(ROS) generation and c-Jun N-terminal kinase(JNK) activation in human hepatocellular carcinoma cells...AIM:To investigate whether the apoptotic activities of 8-bromo-7-methoxychrysin(BrMC) involve reactive oxygen species(ROS) generation and c-Jun N-terminal kinase(JNK) activation in human hepatocellular carcinoma cells(HCC).METHODS:HepG2,Bel-7402 and L-02 cell lines were cultured in vitro and the apoptotic effects of BrMC were evaluated by flow cytometry(FCM) after propidium iodide(PI) staining,caspase-3 activity using enzymelinked immunosorbent assay(ELISA),and DNA agarose gel electrophoresis.ROS production was evaluated by FCM after dichlorodihydrofluorescein diacetate(DCHFDA) probe labeling.The phosphorylation level of JNK and c-Jun protein was analyzed by Western blotting.RESULTS:FCM after PI staining showed a dose-dependent increase in the percentage of the sub-G1 cell pop-ulation(P < 0.05),reaching 39.0% ± 2.8% of HepG2 cells after 48 h of treatment with BrMC at 10 μmol/L.The potency of BrMC to HepG2 and Bel-7402(32.1% ± 2.6%) cells was found to be more effective than the lead compound,chrysin(16.2% ± 1.6% for HepG2 cells and 11.0% ± 1.3% for Bel-7402 cell) at 40 μmol/L and similar to 5-flurouracil(33.0% ± 2.1% for HepG2 cells and 29.3% ± 2.3% for Bel-7402 cells) at 10 μmol/L.BrMC had little effect on human embryo liver L-02 cells,with the percentage of sub-G1 cell population 5.4% ± 1.8%.Treatment of HepG2 cells with BrMC for 48 h also increased the levels of active caspase-3,in a concentration-dependent manner.z-DEVD-fmk,a caspase-3specific inhibitor,prevented the activation of caspase-3.Treatment with BrMC at 10 μmol/L for 48 h resulted in the formation of a DNA ladder.Treatment of cells with BrMC(10 μmol/L) increased mean fluorescence intensity of DCHF-DA in HepG2 cells from 7.2 ± 1.12 at 0 h to 79.8 ± 3.9 at 3 h and 89.7 ± 4.7 at 6 h.BrMC did not affect ROS generation in L-02 cells.BrMC treatment failed to induce cell death and caspase-3 activation in HepG2 cells pretreated with N-acetylcysteine(10 mmol/L).In addition,in HepG2 cells treated with BrMC(2.5,5.0,10.0 μmol/L) for 12 h,JNK activation was observed.Peak JNK activation occurred at 12 h post-treatment and this activation persisted for up to 24 h.The expression of phosphorylated JNK and c-Jun protein after 12 h with BrMC-treated cells was inhibited by N-acetylcysteine and SP600125 pre-treatment,but GW9662 had no effect.SP600125 substantially reduced BrMC-induced cell death and caspase-3 activation of HepG2 cells.N-acetylcysteine and GW9662 also attenuated induction of cell death and caspase-3 activation in HepG2 cells treated with BrMC.CONCLUSION:BrMC induces apoptosis of HCC cells by ROS generation and sustained JNK activation.展开更多
Ten gem-difluoromethylenated chrysin derivatives were prepared and their anticancer activities in vitro were evaluated by the standard MTT method. The results of biological test showed that some of gem-difluoromethyle...Ten gem-difluoromethylenated chrysin derivatives were prepared and their anticancer activities in vitro were evaluated by the standard MTT method. The results of biological test showed that some of gem-difluoromethylenated chrysin derivatives had higher anticancer activity than chrysin.展开更多
In this study,we reported the discovery and structure-activity relationship analysis of chrysin derivatives as a new class of inhibitors targeting poly(ADP-ribose)polymerase 1(PARP1).Among these derivatives,compound 5...In this study,we reported the discovery and structure-activity relationship analysis of chrysin derivatives as a new class of inhibitors targeting poly(ADP-ribose)polymerase 1(PARP1).Among these derivatives,compound 5d emerged as the most effective chrysin-based inhibitor of PARP1,with an IC50 value of 108 nmol·L^(-1).This compound significantly inhibited the proliferation and migration of breast cancer cell lines HCC-1937 and MDA-MB-436 by inducing DNA damage.Furthermore,5d induced apoptosis and caused an extended G1/S-phase in these cell lines.Molecular docking studies revealed that 5d possesses a strong binding affinity toward PARP1.In vivo,in a xenograft model,5d effectively reduced tumor growth by downregulating PARP1 expression.Overall,compound 5d shows promise as a potential therapeutic agent for the treatment of BRCA wild-type breast cancer.展开更多
T he effect of the anti-infl ammatory fl avonoid chrysin on osteogenesis was determined in preosteoblast MC3T3-E1 cells.Results demonstrated that chrysin could induce osteogenic differentiation in the absence of other...T he effect of the anti-infl ammatory fl avonoid chrysin on osteogenesis was determined in preosteoblast MC3T3-E1 cells.Results demonstrated that chrysin could induce osteogenic differentiation in the absence of other osteo-genic agents.Chrysin treatment promoted the expres-sion of transcription factors(Runx2 and Osx)and bone formation marker genes(Col1A1,OCN,and OPN)as well as enhanced the formation of mineralized nodules.During osteogenic differentiation,chrysin preferentially activated ERK1/2,but not JNK nor the p38 MAPKs.Further experi-ments with inhibitors revealed the co-treatment of U0126,PD98059,or ICI182780(a general ER antagonist)with chrysin effectively abrogated the chrysin-induced osteo-genesis and ERK1/2 activation.Thus,the effect of chrysin on osteogenesis is ERK1/2-dependent and involves ER.Therefore,chrysin has the signifi cant potential to enhance osteogenesis for osteoporosis prevention and treatment.展开更多
The electrochemical behavior of chrysin in pH 2.0-9.0 Britton-Robinson （B-R） buffer solutions was studied by the means of linear sweep voltammetry and cyclic voltammetry at a static mercury drop electrode. In differ...The electrochemical behavior of chrysin in pH 2.0-9.0 Britton-Robinson （B-R） buffer solutions was studied by the means of linear sweep voltammetry and cyclic voltammetry at a static mercury drop electrode. In different pH range of B-R buffer solutions, chrysin could cause four reduction waves. In pH 2.0-5.8 B-R buffer solutions, wave P1 yielded by chrysin is a one-electron reduction wave, and wave P1 caused by further reduction of the products of wave P1 in pH〈3.0 B-R buffer solution is also a one-electron reduction wave. But in 3.0〈pH〈5.8 B-R buffer solution wave P1 was overlapped by the hydrogen wave. Between pH 5.8 and 9.0, chrysin could yield two reduction waves P2 and P3- The former is an irreversible adsorptive wave of ionized chrysin involving one electron and the latter is also an irreversible adsorptive wave of reduction intermediate radical of chrysin involving one electron and one proton. And a linear relationship between ip3 and the concentration of chrysin can be established from 1.0×10^-6 to 4.0×10^-5 mol·L^-1 （r=0.9924） with the detection limit of 5×10^-7 mol·L^-1. In addition, the antioxidant ability of chrysin was investigated by linear sweep voltammetry （LSV）. The determination result of IC50 of chrysin showed that chrysin is a good antioxidant.展开更多
The host-guest interaction between cucurbit[8]uril（Q[8]） and chrysin（CHR） has been studied by means of 1H NMR, mass spectrometry（MS）, differential thermal analysis（DTA）, and UV-Vis spectrophotometry. The resul...The host-guest interaction between cucurbit[8]uril（Q[8]） and chrysin（CHR） has been studied by means of 1H NMR, mass spectrometry（MS）, differential thermal analysis（DTA）, and UV-Vis spectrophotometry. The results show that CHR forms a 1：1 inclusion complex with Q[8], with a binding constant of CHR with Q[8] by UV absorp- tion being 5.4 × 106. Phase solubility experiments show a 5.13-fold increase in the solubility of CHR through interac- tion with Q[8] {c（Q[8]）=10-4 real/L}. A study of the evolution of UV absorption spectra with time shows that Q[8] significantly increases the stability of CHR. The antioxidant activity of CHR-Q[8] has been tested by the ABTS me- thod. The CHR-Q[8] inclusion complex shows a better scavenging effect towards the ABTS radical than CHR, with respective IC50 values of 1.05 ×10-6 and 3.07× 10-6 mol/L. In vitro release studies have shown that CHR-Q[8] has a sustained release effcct.展开更多
Among current novel druggable targets,proteineprotein interactions(PPIs)are of considerable and growing interest.Diacylglycerol kinase a(DGKα)interacts with focal adhesion kinase(FAK)band 4.1-ezrin-radixin-moesin(FER...Among current novel druggable targets,proteineprotein interactions(PPIs)are of considerable and growing interest.Diacylglycerol kinase a(DGKα)interacts with focal adhesion kinase(FAK)band 4.1-ezrin-radixin-moesin(FERM)domain to induce the phosphorylation of FAK Tyr397 site and promotes the malignant progression of esophageal squamous cell carcinoma(ESCC)cells.Chrysin is a multi-functional bioactive flavonoid,and possesses potential anticancer activity,whereas little is known about the anticancer activity and exact molecular mechanisms of chrysin in ESCC treatment.In this study,we found that chrysin significantly disrupted the DGKα/FAK signalosome to inhibit FAKcontrolled signaling pathways and the malignant progression of ESCC cells both in vitro and in vivo,whereas produced no toxicity to the normal cells.Molecular validation specifically demonstrated that Asp435 site in the catalytic domain of DGKαcontributed to chrysin-mediated inhibition of the assembly of DGKα/FAK complex.This study has illustrated DGKα/FAK complex as a target of chrysin for the first time,and provided a direction for the development of natural products-derived PPIs inhibitors in tumor treatment.展开更多
Uveitis is a common cause of blindness worldwide.Experimental autoimmune uveitis(EAU)is an animal model of noninfectious uveitis.Chrysin(5,7-dihydroxyflavone)is a member of the flavonoid family and has anti-inflammato...Uveitis is a common cause of blindness worldwide.Experimental autoimmune uveitis(EAU)is an animal model of noninfectious uveitis.Chrysin(5,7-dihydroxyflavone)is a member of the flavonoid family and has anti-inflammatory effects.We immunized C57BL/6J mice with human interphotoreceptor retinoid-binding protein peptide 1–20 to induce EAU.Chrysin was administered intragastrically at 25 mg/kg daily to the chrysin-treated mice from 3 days before immunization to 21 days after immunization.Vehicle was administered to the mice in the control group according to the same protocol.Lower clinical and histopathological scores,increased integrity of the blood–retinal barrier(BRB)and higher expression of tight junction proteins were observed in the chrysin-treated mice.Chrysin significantly decreased the proportions of Th1,Th17 and CD4^(+)CD3^(+)CD62L^(+)Th0 cells,and increased the proportion of Treg cells.Both macrophage infiltration and the expression of inducible nitric oxide synthase in the retina were efficiently inhibited by chrysin treatment.In chrysin-treated mice,the expression of interferon-γ,interleukin(IL)-17A,IL-6,IL-1βand tumor necrosis factor-αwas reduced in the retina,whereas higher levels of transforming growth factor-βwere detected.Furthermore,NF-κBp65 was downregulated after chrysin treatment.In conclusion,as an anti-inflammatory molecule,chrysin exerts a preventive effect on EAU by modulating the balance among helper T-cell subsets and suppressing ocular inflammation,thereby maintaining the integrity of the BRB.展开更多
Two series of 7-O-modified chrysin derivatives were prepared from 7-O-carboxymethy! chrysin（2a）, 7-O-carboxypropylchrysin（2b） and short-chain alcohols by using 1-ethyl-3-（3-dimethylaminopropyl）carbodiimide hydro...Two series of 7-O-modified chrysin derivatives were prepared from 7-O-carboxymethy! chrysin（2a）, 7-O-carboxypropylchrysin（2b） and short-chain alcohols by using 1-ethyl-3-（3-dimethylaminopropyl）carbodiimide hydrochloride（EDCI）, N-hydroxybenzotriazole（HOBt） and 4-dimethylamiopryidine（DMAP） as coupling reagents. Taking cisplatin as a reference substance, their anti-proliferative activities in vitro against human gastric carcinoma MGC-803 cells were evaluated by the standard 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyl-2H-tetrazolium bromide （MTT） method. The results show that among the compounds tested, hepty 4-（5-hydroxy-4-oxo-2-phenyl-4H- chromen-7-yloxy） acetate（3f） displayed the most potent growth-inhibitory effect on MGC-803 cells with half maximal inhibitory concentration（ICso） value of 3.23 pmol/L. The preliminary mechanism of inhibitory effect of compound 3f was also detected by flow cytometry（FCM）, and the compound exerted anti- cancer activity via inducing the apoptosis of MGC-803 cells in a dose dependent manner, which suggested that compound 3f would be a potential anti-cancer agent.展开更多
Objective: To design and synthesize a series of chrysin derivatives and evaluate the antitumor activities with MTT assay, so as to investigate molecular structure-activity relationship with molecular docking.Methods: ...Objective: To design and synthesize a series of chrysin derivatives and evaluate the antitumor activities with MTT assay, so as to investigate molecular structure-activity relationship with molecular docking.Methods: Target products were synthesized with high yield by substitution reaction, hydrolysis reaction,esterification reaction, and saponification reaction in sequence, and activities of all compounds were evaluated with human gastric carcinoma cell lines MGC-803 and human breast carcinoma cell lines MCF-7 through standard MTT assay. Molecular docking results were calculated with Surflex Geom X programme of Sybyl X-2.0 version workstation.Results: 7-O-amino acids chrysin derivatives 6 a–6 l were synthesized and their inhibitory effects were evaluated by comparing the material chrysin with positive control drug 5-fluorouracil(5-FU). Among these derivatives, compound 5 b(IC50= 24.50 ± 2.26 μmol/L), 5 k(IC50= 24.30 ± 2.19 μmol/L), and 6 f(IC50= 24.61 ± 2.01 μmol/L) showed better inhibitory activities against MGC-803 cell lines, and compound 5 g(IC50= 13.15 ± 1.73 μmol/L) and 5 j(IC50= 12.34 ± 1.25 μmol/L) showed better inhibitory activities against MCF-7 cell lines than chrysin and 5-FU. Molecular docking scores showed a credible consistency compared with MTT results.Conclusion: Compounds 5 b, 5 d, 5 g, 5 j, 5 k, and 6 f showed good antiproliferative effects on specific tumor cells, and compound 5 g should be researched further when according to molecular docking.展开更多
文摘AIM： To investigate the effect of 5, 7-dihydroxy-8- nitrochrysin （NOChR） on apoptosis of human gastric carcinoma SGC-7901 cell line.METHODS： SGC-7901 cells were cultured in vitro and the inhibitory effect of NOChR on proliferation of SGC-7901 cells was measured by using an Ml-r assay. NOChR-induced apoptosis rate of SGC-7901 cells was detected using flow cytometry （FCM） with PI staining. DNA ladder bands were observed by DNA agarose gel electrophoresis. The influence of NOChR on the proxisome proliferator-activated receptor-γ （PPARγ）, Bcl-2 and Bax protein expression of SGC-7901 cells was analyzed by Western blot.RESULTS： MIF assay showed that NOChR markedly inhibited proliferation of SGC-7901 cells in a dose- dependent manner, and when ICso was 4.14 μmol/L, the potency of NOChR was 10 times than that of lead compound, chrysin （ChR, IC50 was 40.56 μmol/L）, and was similar to 5-fluorouracil （5-FU, IC50 was 4.51 μmol/L）. FCM with propidium iodide （PI） staining demonstrated that the apoptosis rates of SGC-7901 cells treated with 1.25, 5.00 and 20.00 μmol/L NOChR for 48 h were 9.8% 4- 0.2%, 36.8% 4- 1.9% and 45.5% 4- 3.5%, respectively, and were significantly higher when treated with 5.00 and 20.00 μmol/L NOChR than that with 20.00 μmol/L ChR （12.9% 4- 1.5%）. DNA agarose gel electrophoresis showed that treatment of SGC-7901 cells with 20.00 μmol/L NOChR for 48 h resulted in typical DNA ladder bands of DNA of SGC-7901 cells, which could be eliminated by treating with 10.00 μmol/L GW9662, a blocker of PPARy. Western blot analysis revealed that after 24 h of treatment with 20.00 μmol/L NOChR, PPARgamma and Bax protein expression of SGC-7901 cells increased but Bcl-2 expression decreased; however, pre-incubation with 10.00 μmol/L GW9662 could efficiently antagonize and weaken the regulatory effect of 20.00 μmol/L NOChR on Bax and Bcl-2 protein expression of SGC-7901 cells. CONCLUSION： NOChR induces apoptosis of SGO7901 cell lines by activating PPARy and decreasing ratio of Bcl-2 to Bax.
基金Supported by Research Grant of Department of Science and Technology of Hunan Province,2007TP4017
文摘AIM： To investigate the effect of 5-allyl-7-gen-difluoromethylenechrysin （ADFMChR） on apoptosis of human liver carcinoma HepG2 cell line and the molecular mechanisms involved.METHODS： HepG2 cells and L-02 cells were cultured in vitro and the inhibitory effect of ADFMChR on their proliferation was measured by MTT assay. The apoptosis of HepG2 cells was determined by flow cytometry （FCM） using propidium iodide （PI） fluorescence staining. DNA ladder bands were observed by DNA agarose gel electrophoresis. The influence of ADFMChR on the proxisome proliferator-activated receptor γ （PPARγ）, NF-κB, Bcl-2 and Bax protein expression of HepG2 cells were analyzed by Western blotting.RESULTS： MTT assay showed that ADFMChR significantly inhibited proliferation of HepG2 cells in a dose- dependent manner, with little effect on growth of L-02 cells, and when ICs0 was measured as 8.45 μmol/L and 191.55 μmol/L respectively, the potency of ADFMChR to HepG2 cells, was found to be similar to 5-fluorouracil （5-FU, ICso was 9.27 μmol/L）. The selective index of ADFMChR cytotoxicity to HepG2 cells was 22.67 （191.55/8.45）, higher than 5-FU （SI was 7.05 （65.37/9.27）. FCM with PI staining demonstrated that the apoptosis rates of HepG2 cells treated with 3.0, 10.0 and 30.0 μmol/L ADFMChR for 48 h were 5.79%, 9.29% and 37.8%, respectively, and were significantly higher when treated with 30.0 μmol/L ADFMChR than when treated with 30.0 μmol/L ChR （16.0%） （P 〈 0.05） and were similar to those obtained with 30.0 μmol/L 5-FU（41.0%）. DNA agarose gel electrophoresis showed that treatment of HepG2 cells with 10.0 μmol/L ADFMChR for 48 h and 72 h resulted in typical DNA ladders which could be reversed by 10.00 pmol/1 GW9662, a blocker of PPARy. Western blotting analysis revealed that aEer 24 h of treatment with 3.0, 10.0, 30.0 μmol/L ADFMChR, PPARy and Bax protein expression in HepG2 cells increased but Bcl-2 and NF-κB expression decreased; however, pre-incubation with 10.0 μmol/L GW9662 could efficiently antagonize and weaken the regulatory effect of 3.0, 30.0 μmol/L ADFMChR on PPARy and NF-KB protein expression in HepG2 cells.CONCLUSION： ADFMChR induces apoptosis of HepG2 cell lines by activating PPARγ, inhibiting protein expression of Bcl-2 and NF-κB, and increasing Bax expression.
文摘Chrysin(1) and tectochrysin(2) were respectively synthesized in four steps from 1,3,5-tribromobenzene in an overall yield of 46.8% and that of 37.0% with the key step being the Bu_4NBr catalyzed hydrolysis of 1-phenyl-3-(2′,4′,6′-trimethoxyphenyl)-1, 3-propanedione (11) under different conditions.
基金Supported by Hunan Provincial Natural Science Foundation of China,No.03JJY5009
文摘AIM:To investigate whether the apoptotic activities of 8-bromo-7-methoxychrysin(BrMC) involve reactive oxygen species(ROS) generation and c-Jun N-terminal kinase(JNK) activation in human hepatocellular carcinoma cells(HCC).METHODS:HepG2,Bel-7402 and L-02 cell lines were cultured in vitro and the apoptotic effects of BrMC were evaluated by flow cytometry(FCM) after propidium iodide(PI) staining,caspase-3 activity using enzymelinked immunosorbent assay(ELISA),and DNA agarose gel electrophoresis.ROS production was evaluated by FCM after dichlorodihydrofluorescein diacetate(DCHFDA) probe labeling.The phosphorylation level of JNK and c-Jun protein was analyzed by Western blotting.RESULTS:FCM after PI staining showed a dose-dependent increase in the percentage of the sub-G1 cell pop-ulation(P < 0.05),reaching 39.0% ± 2.8% of HepG2 cells after 48 h of treatment with BrMC at 10 μmol/L.The potency of BrMC to HepG2 and Bel-7402(32.1% ± 2.6%) cells was found to be more effective than the lead compound,chrysin(16.2% ± 1.6% for HepG2 cells and 11.0% ± 1.3% for Bel-7402 cell) at 40 μmol/L and similar to 5-flurouracil(33.0% ± 2.1% for HepG2 cells and 29.3% ± 2.3% for Bel-7402 cells) at 10 μmol/L.BrMC had little effect on human embryo liver L-02 cells,with the percentage of sub-G1 cell population 5.4% ± 1.8%.Treatment of HepG2 cells with BrMC for 48 h also increased the levels of active caspase-3,in a concentration-dependent manner.z-DEVD-fmk,a caspase-3specific inhibitor,prevented the activation of caspase-3.Treatment with BrMC at 10 μmol/L for 48 h resulted in the formation of a DNA ladder.Treatment of cells with BrMC(10 μmol/L) increased mean fluorescence intensity of DCHF-DA in HepG2 cells from 7.2 ± 1.12 at 0 h to 79.8 ± 3.9 at 3 h and 89.7 ± 4.7 at 6 h.BrMC did not affect ROS generation in L-02 cells.BrMC treatment failed to induce cell death and caspase-3 activation in HepG2 cells pretreated with N-acetylcysteine(10 mmol/L).In addition,in HepG2 cells treated with BrMC(2.5,5.0,10.0 μmol/L) for 12 h,JNK activation was observed.Peak JNK activation occurred at 12 h post-treatment and this activation persisted for up to 24 h.The expression of phosphorylated JNK and c-Jun protein after 12 h with BrMC-treated cells was inhibited by N-acetylcysteine and SP600125 pre-treatment,but GW9662 had no effect.SP600125 substantially reduced BrMC-induced cell death and caspase-3 activation of HepG2 cells.N-acetylcysteine and GW9662 also attenuated induction of cell death and caspase-3 activation in HepG2 cells treated with BrMC.CONCLUSION:BrMC induces apoptosis of HCC cells by ROS generation and sustained JNK activation.
文摘Ten gem-difluoromethylenated chrysin derivatives were prepared and their anticancer activities in vitro were evaluated by the standard MTT method. The results of biological test showed that some of gem-difluoromethylenated chrysin derivatives had higher anticancer activity than chrysin.
基金This work was supported by the Clinical Research Center for Breast&Thyroid Disease Prevention in Hunan Province(No.2018SK4001)the Scientific Research Project of Hunan Provincial Health Commission(No.20201969)。
文摘In this study,we reported the discovery and structure-activity relationship analysis of chrysin derivatives as a new class of inhibitors targeting poly(ADP-ribose)polymerase 1(PARP1).Among these derivatives,compound 5d emerged as the most effective chrysin-based inhibitor of PARP1,with an IC50 value of 108 nmol·L^(-1).This compound significantly inhibited the proliferation and migration of breast cancer cell lines HCC-1937 and MDA-MB-436 by inducing DNA damage.Furthermore,5d induced apoptosis and caused an extended G1/S-phase in these cell lines.Molecular docking studies revealed that 5d possesses a strong binding affinity toward PARP1.In vivo,in a xenograft model,5d effectively reduced tumor growth by downregulating PARP1 expression.Overall,compound 5d shows promise as a potential therapeutic agent for the treatment of BRCA wild-type breast cancer.
文摘T he effect of the anti-infl ammatory fl avonoid chrysin on osteogenesis was determined in preosteoblast MC3T3-E1 cells.Results demonstrated that chrysin could induce osteogenic differentiation in the absence of other osteo-genic agents.Chrysin treatment promoted the expres-sion of transcription factors(Runx2 and Osx)and bone formation marker genes(Col1A1,OCN,and OPN)as well as enhanced the formation of mineralized nodules.During osteogenic differentiation,chrysin preferentially activated ERK1/2,but not JNK nor the p38 MAPKs.Further experi-ments with inhibitors revealed the co-treatment of U0126,PD98059,or ICI182780(a general ER antagonist)with chrysin effectively abrogated the chrysin-induced osteo-genesis and ERK1/2 activation.Thus,the effect of chrysin on osteogenesis is ERK1/2-dependent and involves ER.Therefore,chrysin has the signifi cant potential to enhance osteogenesis for osteoporosis prevention and treatment.
基金Project supported by the National Natural Science Foundation of-China （No. 20275030） and the Natural Science Foundation of Shaanxi Province（No.2004B20）.
文摘The electrochemical behavior of chrysin in pH 2.0-9.0 Britton-Robinson （B-R） buffer solutions was studied by the means of linear sweep voltammetry and cyclic voltammetry at a static mercury drop electrode. In different pH range of B-R buffer solutions, chrysin could cause four reduction waves. In pH 2.0-5.8 B-R buffer solutions, wave P1 yielded by chrysin is a one-electron reduction wave, and wave P1 caused by further reduction of the products of wave P1 in pH〈3.0 B-R buffer solution is also a one-electron reduction wave. But in 3.0〈pH〈5.8 B-R buffer solution wave P1 was overlapped by the hydrogen wave. Between pH 5.8 and 9.0, chrysin could yield two reduction waves P2 and P3- The former is an irreversible adsorptive wave of ionized chrysin involving one electron and the latter is also an irreversible adsorptive wave of reduction intermediate radical of chrysin involving one electron and one proton. And a linear relationship between ip3 and the concentration of chrysin can be established from 1.0×10^-6 to 4.0×10^-5 mol·L^-1 （r=0.9924） with the detection limit of 5×10^-7 mol·L^-1. In addition, the antioxidant ability of chrysin was investigated by linear sweep voltammetry （LSV）. The determination result of IC50 of chrysin showed that chrysin is a good antioxidant.
基金Supported by the National Natural Science Foundation of China（No.21272045）.
文摘The host-guest interaction between cucurbit[8]uril（Q[8]） and chrysin（CHR） has been studied by means of 1H NMR, mass spectrometry（MS）, differential thermal analysis（DTA）, and UV-Vis spectrophotometry. The results show that CHR forms a 1：1 inclusion complex with Q[8], with a binding constant of CHR with Q[8] by UV absorp- tion being 5.4 × 106. Phase solubility experiments show a 5.13-fold increase in the solubility of CHR through interac- tion with Q[8] {c（Q[8]）=10-4 real/L}. A study of the evolution of UV absorption spectra with time shows that Q[8] significantly increases the stability of CHR. The antioxidant activity of CHR-Q[8] has been tested by the ABTS me- thod. The CHR-Q[8] inclusion complex shows a better scavenging effect towards the ABTS radical than CHR, with respective IC50 values of 1.05 ×10-6 and 3.07× 10-6 mol/L. In vitro release studies have shown that CHR-Q[8] has a sustained release effcct.
基金supported by the National Natural Science Foundation of China(81830086,81988101,81772504 and 81972243)Beijing Municipal Commission of Health and Family Planning Project(PXM2018_026279_000005,China)
文摘Among current novel druggable targets,proteineprotein interactions(PPIs)are of considerable and growing interest.Diacylglycerol kinase a(DGKα)interacts with focal adhesion kinase(FAK)band 4.1-ezrin-radixin-moesin(FERM)domain to induce the phosphorylation of FAK Tyr397 site and promotes the malignant progression of esophageal squamous cell carcinoma(ESCC)cells.Chrysin is a multi-functional bioactive flavonoid,and possesses potential anticancer activity,whereas little is known about the anticancer activity and exact molecular mechanisms of chrysin in ESCC treatment.In this study,we found that chrysin significantly disrupted the DGKα/FAK signalosome to inhibit FAKcontrolled signaling pathways and the malignant progression of ESCC cells both in vitro and in vivo,whereas produced no toxicity to the normal cells.Molecular validation specifically demonstrated that Asp435 site in the catalytic domain of DGKαcontributed to chrysin-mediated inhibition of the assembly of DGKα/FAK complex.This study has illustrated DGKα/FAK complex as a target of chrysin for the first time,and provided a direction for the development of natural products-derived PPIs inhibitors in tumor treatment.
基金supported by the National Natural Science Foundation of China(grant numbers 81371038 and 91442124)the Natural Science Foundation of Tianjin(grant 12JCYBJC33900 and 14JCYBJC28000)TMUGH(grant number ZYYFY2015026).
文摘Uveitis is a common cause of blindness worldwide.Experimental autoimmune uveitis(EAU)is an animal model of noninfectious uveitis.Chrysin(5,7-dihydroxyflavone)is a member of the flavonoid family and has anti-inflammatory effects.We immunized C57BL/6J mice with human interphotoreceptor retinoid-binding protein peptide 1–20 to induce EAU.Chrysin was administered intragastrically at 25 mg/kg daily to the chrysin-treated mice from 3 days before immunization to 21 days after immunization.Vehicle was administered to the mice in the control group according to the same protocol.Lower clinical and histopathological scores,increased integrity of the blood–retinal barrier(BRB)and higher expression of tight junction proteins were observed in the chrysin-treated mice.Chrysin significantly decreased the proportions of Th1,Th17 and CD4^(+)CD3^(+)CD62L^(+)Th0 cells,and increased the proportion of Treg cells.Both macrophage infiltration and the expression of inducible nitric oxide synthase in the retina were efficiently inhibited by chrysin treatment.In chrysin-treated mice,the expression of interferon-γ,interleukin(IL)-17A,IL-6,IL-1βand tumor necrosis factor-αwas reduced in the retina,whereas higher levels of transforming growth factor-βwere detected.Furthermore,NF-κBp65 was downregulated after chrysin treatment.In conclusion,as an anti-inflammatory molecule,chrysin exerts a preventive effect on EAU by modulating the balance among helper T-cell subsets and suppressing ocular inflammation,thereby maintaining the integrity of the BRB.
文摘Two series of 7-O-modified chrysin derivatives were prepared from 7-O-carboxymethy! chrysin（2a）, 7-O-carboxypropylchrysin（2b） and short-chain alcohols by using 1-ethyl-3-（3-dimethylaminopropyl）carbodiimide hydrochloride（EDCI）, N-hydroxybenzotriazole（HOBt） and 4-dimethylamiopryidine（DMAP） as coupling reagents. Taking cisplatin as a reference substance, their anti-proliferative activities in vitro against human gastric carcinoma MGC-803 cells were evaluated by the standard 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyl-2H-tetrazolium bromide （MTT） method. The results show that among the compounds tested, hepty 4-（5-hydroxy-4-oxo-2-phenyl-4H- chromen-7-yloxy） acetate（3f） displayed the most potent growth-inhibitory effect on MGC-803 cells with half maximal inhibitory concentration（ICso） value of 3.23 pmol/L. The preliminary mechanism of inhibitory effect of compound 3f was also detected by flow cytometry（FCM）, and the compound exerted anti- cancer activity via inducing the apoptosis of MGC-803 cells in a dose dependent manner, which suggested that compound 3f would be a potential anti-cancer agent.
基金supported by Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study(No.2014-405)Hunan Provincial Department of Education Project(14C1003)
文摘Objective: To design and synthesize a series of chrysin derivatives and evaluate the antitumor activities with MTT assay, so as to investigate molecular structure-activity relationship with molecular docking.Methods: Target products were synthesized with high yield by substitution reaction, hydrolysis reaction,esterification reaction, and saponification reaction in sequence, and activities of all compounds were evaluated with human gastric carcinoma cell lines MGC-803 and human breast carcinoma cell lines MCF-7 through standard MTT assay. Molecular docking results were calculated with Surflex Geom X programme of Sybyl X-2.0 version workstation.Results: 7-O-amino acids chrysin derivatives 6 a–6 l were synthesized and their inhibitory effects were evaluated by comparing the material chrysin with positive control drug 5-fluorouracil(5-FU). Among these derivatives, compound 5 b(IC50= 24.50 ± 2.26 μmol/L), 5 k(IC50= 24.30 ± 2.19 μmol/L), and 6 f(IC50= 24.61 ± 2.01 μmol/L) showed better inhibitory activities against MGC-803 cell lines, and compound 5 g(IC50= 13.15 ± 1.73 μmol/L) and 5 j(IC50= 12.34 ± 1.25 μmol/L) showed better inhibitory activities against MCF-7 cell lines than chrysin and 5-FU. Molecular docking scores showed a credible consistency compared with MTT results.Conclusion: Compounds 5 b, 5 d, 5 g, 5 j, 5 k, and 6 f showed good antiproliferative effects on specific tumor cells, and compound 5 g should be researched further when according to molecular docking.
