BACKGROUND: Enzymes involved in drug and xenobiotic metabolism have been considered to exist in two groups: phase I and phase II enzymes. Cytochrome P450 isoenzymes (CYPs) are the most important phase I enzymes in the...BACKGROUND: Enzymes involved in drug and xenobiotic metabolism have been considered to exist in two groups: phase I and phase II enzymes. Cytochrome P450 isoenzymes (CYPs) are the most important phase I enzymes in the metabolism of xenobiotics. The products of phase I metabolism are then acted upon by phase II enzymes, including glutathione S-transferases (GSTs). Herbs that inhibit CYPs such as CYP3A4 or that induce GSTs may have the potential to protect against chemical carcinogenesis since the mutagenic effects of carcinogens are often mediated through an excess of CYP-generated reactive intermediates. This study was designed to investigate the effects of salvianolic acid B (Sal B), a pure compound extracted from Radix Salviae Miltiorrhizae, a Chinese herb, on cell proliferation and CYP1A2 and CYP3A4 mRNA expression in the presence or absence of rifampicin, a potent inducer of CYPs and GST protein expression in HepG2 cells. METHODS: HepG2 cells were incubated with different concentrations of Sal B. Cell proliferation was determined by SYTOX-Green nucleic acid staining. CYP3A4 and CYP1A2 mRNA expression was assayed by real-time PCR. GST protein expression was analyzed by Western blotting. RESULTS: Low concentrations of Sal B (0-20 μmol/L) had no significant effects on cell proliferation, while higher concentrations (100-250 μmol/L) significantly inhibited proliferation in a concentration-dependent manner. Ten μmol/L Sal B, but not 1 μmol/L, down-regulated CYP3A4 and CYP1A2 mRNA expression after 24 hours of incubation, whereas both 1 and 10 μmol/L Sal B down-regulated CYP3A4mRNA expression after 96 hours of incubation; moreover, 1 and 10 μmol/L Sal B inhibited CYP3A4 mRNA expression induced by rifampicin. Both 1 μmol/L and 10 μmol/L Sal B increased GST expression. CONCLUSION: Sal B inhibits CYP3A4 and CYP1A2 mRNA expression and induces GST expression in HepG2 cells.展开更多
3-脱氧葡糖醛酮(3-Deoxyglucosone,3-DG)是一种高反应性的毒性2-羰基醛化合物,在3-DG还原酶作用下可脱毒生成3-脱氧果糖,在羰基醛脱氢酶作用下脱毒生成3-脱氧葡萄糖醛酸。3-DG代谢酶系统作为一种自身防御系统,可能通过调节3-DG而减少美...3-脱氧葡糖醛酮(3-Deoxyglucosone,3-DG)是一种高反应性的毒性2-羰基醛化合物,在3-DG还原酶作用下可脱毒生成3-脱氧果糖,在羰基醛脱氢酶作用下脱毒生成3-脱氧葡萄糖醛酸。3-DG代谢酶系统作为一种自身防御系统,可能通过调节3-DG而减少美拉德反应的进行和晚期糖基化终末产物(Advanced glycation end products,AGEs)过量生成,并使3-DG处于相对正常水平,这对防止老化病、糖尿病、尿毒症等方面均有积极意义。本文对3-DG代谢酶的来源、分布情况,酶的种类、部分酶学性质及其与临床疾病的关系等研究进展做简要综述。展开更多
High nitrate(NO3-) in vegetables, especially in leaf vegetables poses threaten to human health. Selenium(Se) is an important element for maintaining human health, and exogenous Se application during vegetable and crop...High nitrate(NO3-) in vegetables, especially in leaf vegetables poses threaten to human health. Selenium(Se) is an important element for maintaining human health, and exogenous Se application during vegetable and crop production is an effective way to prevent Se deficiency in human bodies. Exogenous Se shows positive function on plant growth and nutrition uptake under abiotic and/or biotic stresses. However, the influence of exogenous Se on NO3-accumulation in hydroponic vegetables is still not clear. In the present study, hydroponic lettuce plants were subjected to six different concentrations(0, 0.1, 0.5, 5, 10 and 50 μmol L–1) of Se as Na2 Se O3. The effects of Se on NO3-content, plant growth, and photosynthetic capacity of lettuce(Lactuca sativa L.) were investigated. The results showed that exogenous Se positively decreased NO3-content and this effect was concentration-dependent. The lowest NO3-content was obtained under 0.5 μmol L–1 Se treatment. The application of Se enhanced photosynthetic capacity by increasing the photosynthesis rate(Pn), stomatal conductance(Cs) and the transpiration efficiency(Tr) of lettuce. The transportation and assimilation of NO3-and activities of nitrogen metabolism enzymes in lettuce were also analysed. The NO3-efflux in the lettuce roots was markedly increased, but the efflux of NO3-from the root to the shoot was decreased after treated with exogenous Se. Moreover, Se application stimulated NO3-assimilation by enhancing nitrate reductase(NR), nitrite reductase(Ni R), glutamine synthetase(GS) and glutamate synthase enzyme(GOGAT) activities. These results provide direct evidence that exogenous Se shows positive function on decreasing NO3-accumulation via regulating the transport and enhancing activities of nitrogen metabolism enzyme in lettuce. We suggested that 0.5 μmol L–1 Se can be used to reduce NO3-content and increase hydroponic lettuce yield.展开更多
Multidrug resistance (MDR) is a critical problem in cancer chemotherapy. Cancer cells can develop resistance not only to a single cytotoxic drug, but also to entire classes of structurally and functionally unrelated c...Multidrug resistance (MDR) is a critical problem in cancer chemotherapy. Cancer cells can develop resistance not only to a single cytotoxic drug, but also to entire classes of structurally and functionally unrelated compounds. Several mechanisms can mediate the development of MDR, including increased drug efflux from the cells by ABC-transporters (ABCT), activation of metabolic enzymes, and defective pathways towards apoptosis. Many plant secondary metabolites (SMs) can potentially increase sensitivity of drug-resistant cancer cells to chemotherapeutical agents. The present thesis investigates the modulation of MDR by certain medicinal plants and their active compounds. The inhibition of ABCTs (P-gp/MDR1, MRP1, BCRP) and metabolic enzymes (GST and CYP3A4), and the induction of apoptosis are useful indicators of the efficacy of a potential medicinal drug. The focus of this study was the possible mechanisms of drug resistance including: expression of resistance proteins, activation of metabolic enzymes, and alteration of the apoptosis and how to overcome their resistance effect on cancer cells. The overall goal of this review was to evaluate how commonly used medicinal plants and their main active secondary metabolites modulate multidrug resistance in cancer cells in order to validate their uses as anticancer drugs, introduce new therapeutic options for resistant cancer, and facilitate the development of their anticancer strategies and/or combination therapies. In conclusion, SMs from medicinal plants exhibit multitarget activity against MDR-related proteins, metabolic enzymes, and apoptotic signaling, this may help to overcome resistance towards chemotherapeutic drugs.展开更多
基金supported by grants from the National Natural Science Foundation of China (30901943)the Program for New Century Excellent Talents in University (NCET-04-0437)+1 种基金the E-institute of Shanghai Municipal Education Commission (E03008)the Innovative Research Team in Universities of Shanghai Municipal Education Commission
文摘BACKGROUND: Enzymes involved in drug and xenobiotic metabolism have been considered to exist in two groups: phase I and phase II enzymes. Cytochrome P450 isoenzymes (CYPs) are the most important phase I enzymes in the metabolism of xenobiotics. The products of phase I metabolism are then acted upon by phase II enzymes, including glutathione S-transferases (GSTs). Herbs that inhibit CYPs such as CYP3A4 or that induce GSTs may have the potential to protect against chemical carcinogenesis since the mutagenic effects of carcinogens are often mediated through an excess of CYP-generated reactive intermediates. This study was designed to investigate the effects of salvianolic acid B (Sal B), a pure compound extracted from Radix Salviae Miltiorrhizae, a Chinese herb, on cell proliferation and CYP1A2 and CYP3A4 mRNA expression in the presence or absence of rifampicin, a potent inducer of CYPs and GST protein expression in HepG2 cells. METHODS: HepG2 cells were incubated with different concentrations of Sal B. Cell proliferation was determined by SYTOX-Green nucleic acid staining. CYP3A4 and CYP1A2 mRNA expression was assayed by real-time PCR. GST protein expression was analyzed by Western blotting. RESULTS: Low concentrations of Sal B (0-20 μmol/L) had no significant effects on cell proliferation, while higher concentrations (100-250 μmol/L) significantly inhibited proliferation in a concentration-dependent manner. Ten μmol/L Sal B, but not 1 μmol/L, down-regulated CYP3A4 and CYP1A2 mRNA expression after 24 hours of incubation, whereas both 1 and 10 μmol/L Sal B down-regulated CYP3A4mRNA expression after 96 hours of incubation; moreover, 1 and 10 μmol/L Sal B inhibited CYP3A4 mRNA expression induced by rifampicin. Both 1 μmol/L and 10 μmol/L Sal B increased GST expression. CONCLUSION: Sal B inhibits CYP3A4 and CYP1A2 mRNA expression and induces GST expression in HepG2 cells.
文摘3-脱氧葡糖醛酮(3-Deoxyglucosone,3-DG)是一种高反应性的毒性2-羰基醛化合物,在3-DG还原酶作用下可脱毒生成3-脱氧果糖,在羰基醛脱氢酶作用下脱毒生成3-脱氧葡萄糖醛酸。3-DG代谢酶系统作为一种自身防御系统,可能通过调节3-DG而减少美拉德反应的进行和晚期糖基化终末产物(Advanced glycation end products,AGEs)过量生成,并使3-DG处于相对正常水平,这对防止老化病、糖尿病、尿毒症等方面均有积极意义。本文对3-DG代谢酶的来源、分布情况,酶的种类、部分酶学性质及其与临床疾病的关系等研究进展做简要综述。
基金supported by the National High-Tech R&D Program of China(863 Program,2013AA103004)the International S&T Cooperation Program of China(2014DFG32110)the National Key Research and Development Program of China(2014BAD08B020106)
文摘High nitrate(NO3-) in vegetables, especially in leaf vegetables poses threaten to human health. Selenium(Se) is an important element for maintaining human health, and exogenous Se application during vegetable and crop production is an effective way to prevent Se deficiency in human bodies. Exogenous Se shows positive function on plant growth and nutrition uptake under abiotic and/or biotic stresses. However, the influence of exogenous Se on NO3-accumulation in hydroponic vegetables is still not clear. In the present study, hydroponic lettuce plants were subjected to six different concentrations(0, 0.1, 0.5, 5, 10 and 50 μmol L–1) of Se as Na2 Se O3. The effects of Se on NO3-content, plant growth, and photosynthetic capacity of lettuce(Lactuca sativa L.) were investigated. The results showed that exogenous Se positively decreased NO3-content and this effect was concentration-dependent. The lowest NO3-content was obtained under 0.5 μmol L–1 Se treatment. The application of Se enhanced photosynthetic capacity by increasing the photosynthesis rate(Pn), stomatal conductance(Cs) and the transpiration efficiency(Tr) of lettuce. The transportation and assimilation of NO3-and activities of nitrogen metabolism enzymes in lettuce were also analysed. The NO3-efflux in the lettuce roots was markedly increased, but the efflux of NO3-from the root to the shoot was decreased after treated with exogenous Se. Moreover, Se application stimulated NO3-assimilation by enhancing nitrate reductase(NR), nitrite reductase(Ni R), glutamine synthetase(GS) and glutamate synthase enzyme(GOGAT) activities. These results provide direct evidence that exogenous Se shows positive function on decreasing NO3-accumulation via regulating the transport and enhancing activities of nitrogen metabolism enzyme in lettuce. We suggested that 0.5 μmol L–1 Se can be used to reduce NO3-content and increase hydroponic lettuce yield.
文摘Multidrug resistance (MDR) is a critical problem in cancer chemotherapy. Cancer cells can develop resistance not only to a single cytotoxic drug, but also to entire classes of structurally and functionally unrelated compounds. Several mechanisms can mediate the development of MDR, including increased drug efflux from the cells by ABC-transporters (ABCT), activation of metabolic enzymes, and defective pathways towards apoptosis. Many plant secondary metabolites (SMs) can potentially increase sensitivity of drug-resistant cancer cells to chemotherapeutical agents. The present thesis investigates the modulation of MDR by certain medicinal plants and their active compounds. The inhibition of ABCTs (P-gp/MDR1, MRP1, BCRP) and metabolic enzymes (GST and CYP3A4), and the induction of apoptosis are useful indicators of the efficacy of a potential medicinal drug. The focus of this study was the possible mechanisms of drug resistance including: expression of resistance proteins, activation of metabolic enzymes, and alteration of the apoptosis and how to overcome their resistance effect on cancer cells. The overall goal of this review was to evaluate how commonly used medicinal plants and their main active secondary metabolites modulate multidrug resistance in cancer cells in order to validate their uses as anticancer drugs, introduce new therapeutic options for resistant cancer, and facilitate the development of their anticancer strategies and/or combination therapies. In conclusion, SMs from medicinal plants exhibit multitarget activity against MDR-related proteins, metabolic enzymes, and apoptotic signaling, this may help to overcome resistance towards chemotherapeutic drugs.
