Cryptosporidium is a protozoan parasite belonging to the phylum Apicomplexa that causes self-limiting diarrhea in immunocompetent individuals, and it may also cause chronic and life-threatening diarrhea in those that ...Cryptosporidium is a protozoan parasite belonging to the phylum Apicomplexa that causes self-limiting diarrhea in immunocompetent individuals, and it may also cause chronic and life-threatening diarrhea in those that are immunocompromised[1]. The two main routes of Cryptosporidium transmission are via water and food. At least 30 Cryptosporidium species have been confirmed, including C. andersoni, with more than 70 genotypes of undefined species.展开更多
Ginkgol C17：1 has been shown to inhibit apoptosis and migration of cancer cells,but the underlying mechanisms are not fully elucidated.In this study,we explored whether the inhibitory effects of Ginkgol C17：1 were a...Ginkgol C17：1 has been shown to inhibit apoptosis and migration of cancer cells,but the underlying mechanisms are not fully elucidated.In this study,we explored whether the inhibitory effects of Ginkgol C17：1 were associated with epidermal growth factor receptor（EGFR） and PI3K/Akt signaling.The results showed that EGF treatment increased the phosphorylation of EGFR,PI3 K,Akt,mTOR and NF-κB,and also enhanced the proliferation,migration and invasion of HepG2 cells.Ginkgol C17：1 dose-dependently inhibited EGF-induced phosphorylation/activation of all the key components including EGFR,PI3 K,Akt,mTOR and NF-kB,leading to a significant reduction either of proliferation or migration and invasion of HepG2 cells.Notably,treatment with Ginkgol C17：1 in mice suppressed the growth of tumor mass in vivo,and expression of EGFR in the tumor tissue.The results suggest that Ginkgol C17：1 is a potent tumor inhibiting compound that acts on EGF-induced signal transduction of the PI3K/Akt signaling pathways,and may represent a clinically interesting candidate for cancer therapy.展开更多
Pharmacological activities and adverse side effects of ginkgolic acids(GAs), major components in extracts from the leaves and seed coats of Ginkgo biloba L, have been intensively studied. However, there are few report...Pharmacological activities and adverse side effects of ginkgolic acids(GAs), major components in extracts from the leaves and seed coats of Ginkgo biloba L, have been intensively studied. However, there are few reports on their hepatotoxicity. In the present study, the metabolism and hepatotoxicity of GA(17:1), one of the most abundant components of GAs, were investigated. Kinetic analysis indicated that human and rat liver microsomes shared similar metabolic characteristics of GA(17:1) in phase I and II metabolisms. The drug-metabolizing enzymes involved in GA(17:1) metabolism were human CYP1 A2, CYP3 A4, UGT1 A6, UGT1 A9, and UGT2 B15, which were confirmed with an inhibition study of human liver microsomes and recombinant enzymes. The MTT assays indicated that the cytotoxicity of GA(17:1) in HepG2 cells occurred in a time-and dose-dependent manner. Further investigation showed that GA(17:1) had less cytotoxicity in primary rat hepatocytes than in HepG2 cells and that the toxicity was enhanced through CYP1 A-and CYP3 A-mediated metabolism.展开更多
Ginkgolic acids(GAs), primarily found in the leaves, nuts, and testa of ginkgo biloba, have been identified with suspected allergenic, genotoxic and cytotoxic properties. However, little information is available about...Ginkgolic acids(GAs), primarily found in the leaves, nuts, and testa of ginkgo biloba, have been identified with suspected allergenic, genotoxic and cytotoxic properties. However, little information is available about GAs toxicity in kidneys and the underlying mechanism has not been thoroughly elucidated so far. Instead of GAs extract, the renal cytotoxicity of GA(15 : 1), which was isolated from the testa of Ginkgo biloba, was assessed in vitro by using MDCK cells. The action of GA(15 : 1) on cell viability was evaluated by the MTT and neutral red uptake assays. Compared with the control, the cytotoxicity of GA(15 : 1) on MDCK cells displayed a time-and dose-dependent manner, suggesting the cells mitochondria and lysosomes were damaged. It was confirmed that GA(15 : 1) resulted in the loss of cells mitochondrial trans-membrane potential(ΔΨm). In propidium iodide(PI) staining analysis, GA(15 : 1) induced cell cycle arrest at the G0/G1 and G2/M phases, influencing on the DNA synthesis and cell mitosis. Characteristics of necrotic cell death were observed in MDCK cells at the experimental conditions, as a result of DNA agarose gel electrophoresis and morphological observation of MDCK cells. In conclusion, these findings might provide useful information for a better understanding of the GA(15 : 1) induced renal toxicity.展开更多
Ginkgolic acids are unwanted constituents in standard Ginkgo biloba leaves extracts. Thus, for the quality control of ginkgo extracts, it is important to establish an effective degradation method, with high catalytic ...Ginkgolic acids are unwanted constituents in standard Ginkgo biloba leaves extracts. Thus, for the quality control of ginkgo extracts, it is important to establish an effective degradation method, with high catalytic efficiency and safety, to remove ginkgolic acids.Laccases are oxidases with potential for application in elimination of hazardous phenolic compounds. In this study, single-factor and orthogonal experiments were used to optimize extraction of ginkgolic acid from G. biloba sarcotestae. The results showed that ethanol was the best solvent, with the highest extraction rate for ginkgolic acid at 85% ethanol. On this basis, we measured ethanol volume fraction, extraction time, temperature and solidliquid ratio using an orthogonal experiment. By using absorbance of 310 nm as standard, the optimal extraction conditions were 85% ethanol with, solid-liquid ratio of1:14 at 40°C for 12 h. These conditions gave a ginkgolic acid yield of 73.1 mg·g^(–1). Subsequently, recombinant laccase was used to degrade the ginkgolic acid in several laccase/mediator systems, of which Lac C was the best. At50°C, p H 4.5, enzyme concentration of 0.01 U·m L^(–1),0.5 mmol·L^(–1) mediator ABTS and reaction time of 3 h, the degradation rate of ginkgolic acid reached 100%. These results lay the foundation for research on and application of biological enzymes for detoxification of G. biloba extracts.展开更多
基金supported by the Chinese Special Program for Scientific Research of Public Health [No.201502021 to JC]the National Natural Science Foundation of China [No.81371841 and 81772225 to JC]the Fourth Round of Three-Year Public Health Action Plan of Shanghai,China [No.15GWZK0101 to JC]
文摘Cryptosporidium is a protozoan parasite belonging to the phylum Apicomplexa that causes self-limiting diarrhea in immunocompetent individuals, and it may also cause chronic and life-threatening diarrhea in those that are immunocompromised[1]. The two main routes of Cryptosporidium transmission are via water and food. At least 30 Cryptosporidium species have been confirmed, including C. andersoni, with more than 70 genotypes of undefined species.
基金supported by the National Natural Science Foundation of China(grant no.81372404)the Postdoctoral Foundation of China(grant no.2012M521018)to Yueying Lithe Zhenjiang Social Development Project(No.SH2015072)to Yaxiang Shi
文摘Ginkgol C17：1 has been shown to inhibit apoptosis and migration of cancer cells,but the underlying mechanisms are not fully elucidated.In this study,we explored whether the inhibitory effects of Ginkgol C17：1 were associated with epidermal growth factor receptor（EGFR） and PI3K/Akt signaling.The results showed that EGF treatment increased the phosphorylation of EGFR,PI3 K,Akt,mTOR and NF-κB,and also enhanced the proliferation,migration and invasion of HepG2 cells.Ginkgol C17：1 dose-dependently inhibited EGF-induced phosphorylation/activation of all the key components including EGFR,PI3 K,Akt,mTOR and NF-kB,leading to a significant reduction either of proliferation or migration and invasion of HepG2 cells.Notably,treatment with Ginkgol C17：1 in mice suppressed the growth of tumor mass in vivo,and expression of EGFR in the tumor tissue.The results suggest that Ginkgol C17：1 is a potent tumor inhibiting compound that acts on EGF-induced signal transduction of the PI3K/Akt signaling pathways,and may represent a clinically interesting candidate for cancer therapy.
基金supported by the National Key Project of China(No.2017YFC0908600)the National Natural Science Foundation of China(No.81173120)the National Natural Science Foundation of Zhejiang Province(No.LQ15H310003)
文摘Pharmacological activities and adverse side effects of ginkgolic acids(GAs), major components in extracts from the leaves and seed coats of Ginkgo biloba L, have been intensively studied. However, there are few reports on their hepatotoxicity. In the present study, the metabolism and hepatotoxicity of GA(17:1), one of the most abundant components of GAs, were investigated. Kinetic analysis indicated that human and rat liver microsomes shared similar metabolic characteristics of GA(17:1) in phase I and II metabolisms. The drug-metabolizing enzymes involved in GA(17:1) metabolism were human CYP1 A2, CYP3 A4, UGT1 A6, UGT1 A9, and UGT2 B15, which were confirmed with an inhibition study of human liver microsomes and recombinant enzymes. The MTT assays indicated that the cytotoxicity of GA(17:1) in HepG2 cells occurred in a time-and dose-dependent manner. Further investigation showed that GA(17:1) had less cytotoxicity in primary rat hepatocytes than in HepG2 cells and that the toxicity was enhanced through CYP1 A-and CYP3 A-mediated metabolism.
基金supported by National Natural Science Foundation of China(No.81173120)International Science&Technology Cooperation Program of China(No.2014DFE30050)
文摘Ginkgolic acids(GAs), primarily found in the leaves, nuts, and testa of ginkgo biloba, have been identified with suspected allergenic, genotoxic and cytotoxic properties. However, little information is available about GAs toxicity in kidneys and the underlying mechanism has not been thoroughly elucidated so far. Instead of GAs extract, the renal cytotoxicity of GA(15 : 1), which was isolated from the testa of Ginkgo biloba, was assessed in vitro by using MDCK cells. The action of GA(15 : 1) on cell viability was evaluated by the MTT and neutral red uptake assays. Compared with the control, the cytotoxicity of GA(15 : 1) on MDCK cells displayed a time-and dose-dependent manner, suggesting the cells mitochondria and lysosomes were damaged. It was confirmed that GA(15 : 1) resulted in the loss of cells mitochondrial trans-membrane potential(ΔΨm). In propidium iodide(PI) staining analysis, GA(15 : 1) induced cell cycle arrest at the G0/G1 and G2/M phases, influencing on the DNA synthesis and cell mitosis. Characteristics of necrotic cell death were observed in MDCK cells at the experimental conditions, as a result of DNA agarose gel electrophoresis and morphological observation of MDCK cells. In conclusion, these findings might provide useful information for a better understanding of the GA(15 : 1) induced renal toxicity.
基金supported by the Forestry Achievements of Science and Technology to Promote Projects([2017]10)the Eleventh Six Talents Peak Project of Jiangsu Province(2014-JY-011)a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions
文摘Ginkgolic acids are unwanted constituents in standard Ginkgo biloba leaves extracts. Thus, for the quality control of ginkgo extracts, it is important to establish an effective degradation method, with high catalytic efficiency and safety, to remove ginkgolic acids.Laccases are oxidases with potential for application in elimination of hazardous phenolic compounds. In this study, single-factor and orthogonal experiments were used to optimize extraction of ginkgolic acid from G. biloba sarcotestae. The results showed that ethanol was the best solvent, with the highest extraction rate for ginkgolic acid at 85% ethanol. On this basis, we measured ethanol volume fraction, extraction time, temperature and solidliquid ratio using an orthogonal experiment. By using absorbance of 310 nm as standard, the optimal extraction conditions were 85% ethanol with, solid-liquid ratio of1:14 at 40°C for 12 h. These conditions gave a ginkgolic acid yield of 73.1 mg·g^(–1). Subsequently, recombinant laccase was used to degrade the ginkgolic acid in several laccase/mediator systems, of which Lac C was the best. At50°C, p H 4.5, enzyme concentration of 0.01 U·m L^(–1),0.5 mmol·L^(–1) mediator ABTS and reaction time of 3 h, the degradation rate of ginkgolic acid reached 100%. These results lay the foundation for research on and application of biological enzymes for detoxification of G. biloba extracts.
