Diseases associated with bacterial infection,especially those caused by gram-negative bacteria,have been posing a serious threat to human health.Photodynamic therapy based on aggregation-induced emission(AIE)photosens...Diseases associated with bacterial infection,especially those caused by gram-negative bacteria,have been posing a serious threat to human health.Photodynamic therapy based on aggregation-induced emission(AIE)photosensitizer have recently emerged and provided a promising approach for bacterial discrimination and efficient photodynamic antimicrobial applications.However,they often suffer from the shorter excitation wavelength and lower molar extinction coefficients in the visible region,severely limiting their further applications.Herein,three novel BF_(2)-curcuminoid-based AIE photosensitizers,TBBC,TBC and TBBC-C8,have been rationally designed and successfully developed,in which OCH_(3)-and OC_(8)H_(17)-substituted tetraphenylethene(TPE)groups serve as both electron donor(D)and AIE active moieties,BF_(2)bdk group functions as electron acceptor(A),and styrene(or ethylene)group asπ-bridge in this D-π-A-π-D system,respectively.As expected,these resulting BF_(2)-curcuminoids presented solvent-dependent photophysical properties with large molar extinction coefficients in solutions and excellent AIE properties.Notably,TBBC showed an effective singlet oxygen generation efficiency thanks to the smaller singlet-triplet energy gap(△E_(ST)),and remarkable photostability under green light exposure at 530nm(8.9 mW/cm^(2)).More importantly,TBBC was demonstrated effectiveness in selective staining and photodynamic killing of Escherichia coli(E.coli)in vitro probably due to its optimal molecular size compared with TBC and TBBC-C8.Therefore,TBBC will have great potential as a novel AIE photosensitizer to apply in the discrimination and selective sterilization between Gram-positive and Gram-negative bacteria.展开更多
The growth rate method was adopted to measure the inhibitory effect of curcumin,tetrahydrocurcumin,demethoxycurcumin,and bisdemethoxycurcumin on the mycelial growth of Botrytis cinerea and Colletotrichum gloeosporioid...The growth rate method was adopted to measure the inhibitory effect of curcumin,tetrahydrocurcumin,demethoxycurcumin,and bisdemethoxycurcumin on the mycelial growth of Botrytis cinerea and Colletotrichum gloeosporioides.The results showed that the four curcuminoids inhibited the mycelial growth of the two pathogens in a concentration-dependent manner.Bisdemethoxycurcumin at 600 mg/L exerted the strongest inhibitory effect on the mycelial growth of B.cinerea and C.gloeosporioides,with the relative inhibition rates of 98.19%and 100%,respectively;followed by demethoxycurcumin;curcumin exerted the worst inhibitory effect.Toxicity test results also showed that four curcuminoids all had a certain toxicity to B.cinerea and C.gloeosporioides,among which,bisdemethoxycurcumin exhibited the strongest toxicity,with the EC_(50)of 131.125 and 122.235 mg/L,respectively;while curcumin had the lowest toxicity,with the EC_(50)of 273.143 and 194.943 mg/L,respectively.展开更多
A molecular imprinting polymer technique was successfully applied to precipitation polymerization by using styrene as a functional monomer, curcuminoids as templates, acetonitrile as a porogenic solvent,benzoyl peroxi...A molecular imprinting polymer technique was successfully applied to precipitation polymerization by using styrene as a functional monomer, curcuminoids as templates, acetonitrile as a porogenic solvent,benzoyl peroxide as the initiator, and ethylene glycol dimethacrylate as the crosslinker. The effects of interaction on the adsorption capacity of the molecularly imprinted polymer(MIP) and non-imprinted polymer(NIP) were investigated. A comparison of the adsorption capacity for MIP and NIP indicated that the NIP had the lowest adsorption capacity. The curcuminoid-imprinted polymer(Cur-MIP) was synthesized from 0.0237 mmol of styrene, 47.0 g of acetonitrile, 1.0238 mmol of ethylene glycol dimethacrylate, 0.0325 mmol of curcuminoids, and 0.2480 mmol of benzoyl peroxide. A high-performance liquid chromatography method with fluorescence detection was developed and validated for various chromatographic conditions for the determination of the curcuminoids in turmeric samples. The sample solution was separated using the Cur-MIP via solid-phase extraction and analyzed on a Brownlee analytical C_(18) column(150 mm ×6 mm, 5 mm) using an isocratic elution consisting of acetonitrile and 0.1%trichloroacetic acid(40:60, v/v). The flow rate was maintained at 1.5 m L/min. The fluorescence detector was set to monitor at λex? 426 nm and λem? 539 nm. The quantification limit values were found to be16.66, 66.66, and 33.33 mg/L for curcumin, demethoxycurcumin, and bisdemethoxycurcumin, respectively. Thus, we concluded that the Cur-MIP and high-performance liquid chromatographic-fluorescence method could be applied to selective extraction and could be used as a rapid tool for the determination of curcuminoids in medicinal herbal extracts.展开更多
Curcuminoid difluoroboron has attractive performance as a promising near-infrared（NIR） fluorescent dye. In this contribution, we designed and synthesized a mitochondria-targeted NIR fluorescent probe DFB1 based on d...Curcuminoid difluoroboron has attractive performance as a promising near-infrared（NIR） fluorescent dye. In this contribution, we designed and synthesized a mitochondria-targeted NIR fluorescent probe DFB1 based on difluoroboron curcuminoid scaffold for the detection of Cys（cysteine）. DFB1 employs a curcumin analog as the NIR fluorophore, an acrylate group containing a, b-unsaturated ketone as a functional trigger moiety for Cys, and a triphenylphosphonium（TPP） cation moiety for specifically targeting mitochondria. The remarkable shift of DFB1 with Cys was observed from 470 nm to 590 nm in absorption spectra and from 560 nm to 680 nm in emission spectra. Notably, DFB1 manifests significantly dual-channel and turn-on NIR fluorescent signals simultaneously in response to Cys concentration,which make it favorable for monitoring endogenous Cys activity in vivo. This probe has high sensitivity and selectivity for the detection of Cys over homocysteine（Hcy） and glutathione（GSH）. This specific response for Cys was based on differences kinetics of intramolecular adduct/cyclizations. More importantly, biological experiments indicated that this probe could be utilized for the detection of endogenous mitochondrial Cys in living cells.展开更多
Objective To investigate and compare the action of curcuminoids on the causal pathogens of Candida albicans growth. Methods The effects of curcumin (CUR) and demethoxycurcumin (DMC) on C. albicans growth were first in...Objective To investigate and compare the action of curcuminoids on the causal pathogens of Candida albicans growth. Methods The effects of curcumin (CUR) and demethoxycurcumin (DMC) on C. albicans growth were first investigated and compared by microcalorimetry coupled with multiple analytical methods. The quantitative thermo-kinetic parameters obtained from these curves were analyzed to show difference of the actions. Results By analyzing the main parameters screened from principal component analysis together with 50% inhibiting concentration values, it was demonstrated that both CUR and DMC showed good antifungal activities and CUR was stronger. It was further concluded from structure-activity relationship that the existence of methoxy group might enhance lipophilicity of the mother nucleus, which made it easier for the molecular to enter into the cell membrane of fungi to inhibit its growth. Conclusion This study provides a new method for screening new antifungal agents with high efficacy and low toxicity. Meanwhile, it contributes to the application of curcuminoids as food additive, colorant, and drug. Microcalorimetry is real-time, online, and dynamic, and it could be used to characterize the subtle difference among the effects of synthetic and natural products on the vital process of fungi.展开更多
Objective:The present study aimed to evaluate the effect of a high water-soluble curcuminoids-rich extract(CRE)in a solid dispersion form(CRE-SD)using polyvinylpyrrolidone K30 on osteogenic induction of MC3T3-E1 cells...Objective:The present study aimed to evaluate the effect of a high water-soluble curcuminoids-rich extract(CRE)in a solid dispersion form(CRE-SD)using polyvinylpyrrolidone K30 on osteogenic induction of MC3T3-E1 cells.Methods:CRE was pre-purified using a microwave assisted extraction couple with a Diaion;HP-20 column chromatography.The osteoblastic cell proliferation and differentiation potentials of CRE-SD in MC3T3-E1 cells were tested by cell viability,alkaline phosphatase(ALP)activity,and Alizarin red S activity assays.The m RNA expressions of osteoblast-specific genes and underline mechanisms were assessed by a real time PCR and western blot analysis.Results:CRE-SD 50μg/m L increased alkaline phosphatase(ALP)activity,an early differentiation marker of osteoblasts in both MC3T3-E1 cells and non-osteogenic mouse pluripotent cell line,C3H10T1/2,indicating the action of CRE-SD was not cell-type specific.Alizarin red S activity showed a significant amount of calcium deposition in cells treated with CRE-SD.CRE-SD also upregulated the m RNA expression levels of transcription factors that favor osteoblast differentiation including Bmp-2,Runx2 and Collagen 1 a,in a dose dependent manner.Western blot analysis revealed that noggin attenuated CRE-SD-promoted expressions of Bmp-2 and Runx2 proteins.si RNA mediated blocking of Wnt/β-catenin signaling pathway also annulled the influence of CRE-SD,indicating Wnt/β-catenin dependent activity.Inhibition of the different signaling pathways abolished the influence of CRE-SD on ALP activity,confirming that CRE-SD induced MC3T3-E1 cells into osteoblasts through Wnt/β-catenin and BMP signaling pathway.Conclusion:These results collectively demonstrate that CRE-SD may be a potential therapeutic agent for the treatment of osteoporosis.展开更多
Leaf and tuber extracts of Curcuma wenyujin contain a mixture of curcuminoids.However,the curcuminoid constituents and their molecular mechanisms are poorly understood,and the relevant curcumin synthases remain unclea...Leaf and tuber extracts of Curcuma wenyujin contain a mixture of curcuminoids.However,the curcuminoid constituents and their molecular mechanisms are poorly understood,and the relevant curcumin synthases remain unclear.In this study,we comprehensively compared the metabolite profiles of the leaf and tuber tissues of C.wenyujin.A total of 11 curcuminoid metabolites were identified and exhibited differentially changed contents in the leaf and tuber tissues.An integrated analysis of metabolomic and transcriptomic data revealed the proposed biosynthesis pathway of curcuminoid.Two candidate type III polyketide synthases(PKSs)were identified in the metabolically engineering yeasts,indicating that CwPKS1 and CwPKS2 maintained substrate and product specificities.Especially,CwPKS1 is the first type III PKS identified to synthesize hydrogenated derivatives of curcuminoid,dihydrocurcumin and tetrehydrocurcumin.Interestingly,the substitution of the glycine at position 219 with aspartic acid(G219D mutant)resulted in the complete inactivation of CwPKS1.Our results provide the first comparative metabolome analysis of C.wenyujin and functionally identified type III PKSs,giving valuable information for curcuminoids biosynthesis.展开更多
以姜黄(Curcuma longa L.)组培苗为试材,在继代培养基中添加不同浓度水杨酸(SA)和硝普钠(SNP,NO供体),研究SA和NO对姜黄生长、次生代谢和姜黄素类化合物含量的影响。试验结果表明:SA和NO均能调节姜黄的生长,促进姜黄次生代谢产物的生成;...以姜黄(Curcuma longa L.)组培苗为试材,在继代培养基中添加不同浓度水杨酸(SA)和硝普钠(SNP,NO供体),研究SA和NO对姜黄生长、次生代谢和姜黄素类化合物含量的影响。试验结果表明:SA和NO均能调节姜黄的生长,促进姜黄次生代谢产物的生成;SA 10μmol·L-1或SNP 200μmol·L-1处理时,姜黄叶片叶绿素含量、类胡萝卜素含量和可溶性糖含量均达到最大值,姜黄生长处于最佳状态。SA和NO均能激活苯丙氨酸解氨酶(PAL)、肉桂酸–4–羟化酶(C4H)和4–香豆酸:辅酶A连接酶(4CL)活性,促进姜黄次生代谢途径中咖啡酸、对香豆酸、阿魏酸和肉桂酸的生成,提高双去甲氧基姜黄素、去甲氧基姜黄素和姜黄素含量;因此,SA 10μmol·L-1或SNP 200μmol·L-1最有利于姜黄生长和次生代谢产物的合成。SA和NO对姜黄次生代谢生理调控具有浓度效应。展开更多
基金National Natural Science Foundation of China(No.32101150)Key Scientific Research Project of Higher Education of Henan Province(No.22A430007)+2 种基金Natural Science Foundation of Henan Province(No.222300420501)the Science and Technology Project of Henan Province(No.242102230119)Innovation and Entrepreneurship Training Program for College students in China(No.202310482001).
文摘Diseases associated with bacterial infection,especially those caused by gram-negative bacteria,have been posing a serious threat to human health.Photodynamic therapy based on aggregation-induced emission(AIE)photosensitizer have recently emerged and provided a promising approach for bacterial discrimination and efficient photodynamic antimicrobial applications.However,they often suffer from the shorter excitation wavelength and lower molar extinction coefficients in the visible region,severely limiting their further applications.Herein,three novel BF_(2)-curcuminoid-based AIE photosensitizers,TBBC,TBC and TBBC-C8,have been rationally designed and successfully developed,in which OCH_(3)-and OC_(8)H_(17)-substituted tetraphenylethene(TPE)groups serve as both electron donor(D)and AIE active moieties,BF_(2)bdk group functions as electron acceptor(A),and styrene(or ethylene)group asπ-bridge in this D-π-A-π-D system,respectively.As expected,these resulting BF_(2)-curcuminoids presented solvent-dependent photophysical properties with large molar extinction coefficients in solutions and excellent AIE properties.Notably,TBBC showed an effective singlet oxygen generation efficiency thanks to the smaller singlet-triplet energy gap(△E_(ST)),and remarkable photostability under green light exposure at 530nm(8.9 mW/cm^(2)).More importantly,TBBC was demonstrated effectiveness in selective staining and photodynamic killing of Escherichia coli(E.coli)in vitro probably due to its optimal molecular size compared with TBC and TBBC-C8.Therefore,TBBC will have great potential as a novel AIE photosensitizer to apply in the discrimination and selective sterilization between Gram-positive and Gram-negative bacteria.
文摘The growth rate method was adopted to measure the inhibitory effect of curcumin,tetrahydrocurcumin,demethoxycurcumin,and bisdemethoxycurcumin on the mycelial growth of Botrytis cinerea and Colletotrichum gloeosporioides.The results showed that the four curcuminoids inhibited the mycelial growth of the two pathogens in a concentration-dependent manner.Bisdemethoxycurcumin at 600 mg/L exerted the strongest inhibitory effect on the mycelial growth of B.cinerea and C.gloeosporioides,with the relative inhibition rates of 98.19%and 100%,respectively;followed by demethoxycurcumin;curcumin exerted the worst inhibitory effect.Toxicity test results also showed that four curcuminoids all had a certain toxicity to B.cinerea and C.gloeosporioides,among which,bisdemethoxycurcumin exhibited the strongest toxicity,with the EC_(50)of 131.125 and 122.235 mg/L,respectively;while curcumin had the lowest toxicity,with the EC_(50)of 273.143 and 194.943 mg/L,respectively.
文摘A molecular imprinting polymer technique was successfully applied to precipitation polymerization by using styrene as a functional monomer, curcuminoids as templates, acetonitrile as a porogenic solvent,benzoyl peroxide as the initiator, and ethylene glycol dimethacrylate as the crosslinker. The effects of interaction on the adsorption capacity of the molecularly imprinted polymer(MIP) and non-imprinted polymer(NIP) were investigated. A comparison of the adsorption capacity for MIP and NIP indicated that the NIP had the lowest adsorption capacity. The curcuminoid-imprinted polymer(Cur-MIP) was synthesized from 0.0237 mmol of styrene, 47.0 g of acetonitrile, 1.0238 mmol of ethylene glycol dimethacrylate, 0.0325 mmol of curcuminoids, and 0.2480 mmol of benzoyl peroxide. A high-performance liquid chromatography method with fluorescence detection was developed and validated for various chromatographic conditions for the determination of the curcuminoids in turmeric samples. The sample solution was separated using the Cur-MIP via solid-phase extraction and analyzed on a Brownlee analytical C_(18) column(150 mm ×6 mm, 5 mm) using an isocratic elution consisting of acetonitrile and 0.1%trichloroacetic acid(40:60, v/v). The flow rate was maintained at 1.5 m L/min. The fluorescence detector was set to monitor at λex? 426 nm and λem? 539 nm. The quantification limit values were found to be16.66, 66.66, and 33.33 mg/L for curcumin, demethoxycurcumin, and bisdemethoxycurcumin, respectively. Thus, we concluded that the Cur-MIP and high-performance liquid chromatographic-fluorescence method could be applied to selective extraction and could be used as a rapid tool for the determination of curcuminoids in medicinal herbal extracts.
基金supported by the National Natural Science Foundation of China for Excellent Young Scholars (No. 21622602)Distinguished Young Scholars (No. 21325625)+2 种基金 Oriental Scholarship, Fok Ying Tong Education Foundation (No. 142014)the Fundamental Research Funds for the Central Universities (Nos. WJ1616008, WK1013002)the State Key Laboratory of Fine Chemicals (No. KF1509)
文摘Curcuminoid difluoroboron has attractive performance as a promising near-infrared（NIR） fluorescent dye. In this contribution, we designed and synthesized a mitochondria-targeted NIR fluorescent probe DFB1 based on difluoroboron curcuminoid scaffold for the detection of Cys（cysteine）. DFB1 employs a curcumin analog as the NIR fluorophore, an acrylate group containing a, b-unsaturated ketone as a functional trigger moiety for Cys, and a triphenylphosphonium（TPP） cation moiety for specifically targeting mitochondria. The remarkable shift of DFB1 with Cys was observed from 470 nm to 590 nm in absorption spectra and from 560 nm to 680 nm in emission spectra. Notably, DFB1 manifests significantly dual-channel and turn-on NIR fluorescent signals simultaneously in response to Cys concentration,which make it favorable for monitoring endogenous Cys activity in vivo. This probe has high sensitivity and selectivity for the detection of Cys over homocysteine（Hcy） and glutathione（GSH）. This specific response for Cys was based on differences kinetics of intramolecular adduct/cyclizations. More importantly, biological experiments indicated that this probe could be utilized for the detection of endogenous mitochondrial Cys in living cells.
基金Key Project of Chinese National Program for Fundamental Research and Development(2009ZXJ09004-057,2009ZX09502-022)National Science Foundation of China(81073043)the Open Research Fund of State Key Laboratory Breeding Base of Systematic Research,Development and Utilization of Chinese Medicinal Resource(2011CDKF013)
文摘Objective To investigate and compare the action of curcuminoids on the causal pathogens of Candida albicans growth. Methods The effects of curcumin (CUR) and demethoxycurcumin (DMC) on C. albicans growth were first investigated and compared by microcalorimetry coupled with multiple analytical methods. The quantitative thermo-kinetic parameters obtained from these curves were analyzed to show difference of the actions. Results By analyzing the main parameters screened from principal component analysis together with 50% inhibiting concentration values, it was demonstrated that both CUR and DMC showed good antifungal activities and CUR was stronger. It was further concluded from structure-activity relationship that the existence of methoxy group might enhance lipophilicity of the mother nucleus, which made it easier for the molecular to enter into the cell membrane of fungi to inhibit its growth. Conclusion This study provides a new method for screening new antifungal agents with high efficacy and low toxicity. Meanwhile, it contributes to the application of curcuminoids as food additive, colorant, and drug. Microcalorimetry is real-time, online, and dynamic, and it could be used to characterize the subtle difference among the effects of synthetic and natural products on the vital process of fungi.
基金supported by the Thailand Research Fund (grant number RDG6150075)Prince of Songkla University (grant numbers MET611036S and MET6202025S)
文摘Objective:The present study aimed to evaluate the effect of a high water-soluble curcuminoids-rich extract(CRE)in a solid dispersion form(CRE-SD)using polyvinylpyrrolidone K30 on osteogenic induction of MC3T3-E1 cells.Methods:CRE was pre-purified using a microwave assisted extraction couple with a Diaion;HP-20 column chromatography.The osteoblastic cell proliferation and differentiation potentials of CRE-SD in MC3T3-E1 cells were tested by cell viability,alkaline phosphatase(ALP)activity,and Alizarin red S activity assays.The m RNA expressions of osteoblast-specific genes and underline mechanisms were assessed by a real time PCR and western blot analysis.Results:CRE-SD 50μg/m L increased alkaline phosphatase(ALP)activity,an early differentiation marker of osteoblasts in both MC3T3-E1 cells and non-osteogenic mouse pluripotent cell line,C3H10T1/2,indicating the action of CRE-SD was not cell-type specific.Alizarin red S activity showed a significant amount of calcium deposition in cells treated with CRE-SD.CRE-SD also upregulated the m RNA expression levels of transcription factors that favor osteoblast differentiation including Bmp-2,Runx2 and Collagen 1 a,in a dose dependent manner.Western blot analysis revealed that noggin attenuated CRE-SD-promoted expressions of Bmp-2 and Runx2 proteins.si RNA mediated blocking of Wnt/β-catenin signaling pathway also annulled the influence of CRE-SD,indicating Wnt/β-catenin dependent activity.Inhibition of the different signaling pathways abolished the influence of CRE-SD on ALP activity,confirming that CRE-SD induced MC3T3-E1 cells into osteoblasts through Wnt/β-catenin and BMP signaling pathway.Conclusion:These results collectively demonstrate that CRE-SD may be a potential therapeutic agent for the treatment of osteoporosis.
基金supported by the National Natural Science Foundation of China(82173919,82104320)the Natural Science Foundation of Zhejiang Province(LY21C050004,LQ22H280013).
文摘Leaf and tuber extracts of Curcuma wenyujin contain a mixture of curcuminoids.However,the curcuminoid constituents and their molecular mechanisms are poorly understood,and the relevant curcumin synthases remain unclear.In this study,we comprehensively compared the metabolite profiles of the leaf and tuber tissues of C.wenyujin.A total of 11 curcuminoid metabolites were identified and exhibited differentially changed contents in the leaf and tuber tissues.An integrated analysis of metabolomic and transcriptomic data revealed the proposed biosynthesis pathway of curcuminoid.Two candidate type III polyketide synthases(PKSs)were identified in the metabolically engineering yeasts,indicating that CwPKS1 and CwPKS2 maintained substrate and product specificities.Especially,CwPKS1 is the first type III PKS identified to synthesize hydrogenated derivatives of curcuminoid,dihydrocurcumin and tetrehydrocurcumin.Interestingly,the substitution of the glycine at position 219 with aspartic acid(G219D mutant)resulted in the complete inactivation of CwPKS1.Our results provide the first comparative metabolome analysis of C.wenyujin and functionally identified type III PKSs,giving valuable information for curcuminoids biosynthesis.
