Lanosterol and ergosterol are the active principles with potential pharmacological activities in Inonotus obliquus. However, the two sterols are less accumulated in cultured mycelia of the fungus. In this study, diffe...Lanosterol and ergosterol are the active principles with potential pharmacological activities in Inonotus obliquus. However, the two sterols are less accumulated in cultured mycelia of the fungus. In this study, different carbon and nitrogen sources and pH levels together with three metal ions were assayed for their effects on accumulation of the two sterols in the fungus. Among the tested media the growth medium consisting of glucose (1.5%), rice powder (0.5%), yeast extract (0.4%), wheat bran (0.1%), KH2PO4 (0.01%) and MgSO4·7H2O (0.05%) with pH level at 6.5 yielded a maximum production of the two sterols, which can further be increased following the treatment of Ag+, Cu2+ and Ca2+. Supplementing Ag+ at concentrations of 0.28 and 0.35μmol partially inhibited ergosterol biosynthesis, leading to an enhanced accumulation of lanosterol, the presence of intermediates of ergosterol biosynthetic pathway and a reduced accumulation of ergosterol in cultured mycelia of I.展开更多
Phenolic compounds from field-grown Inonotus obliquus sclerotia (Chaga) consist mainly of hispidin analogs and melanins, and are thought to be the active constituents to treat several human diseases. In submerged cult...Phenolic compounds from field-grown Inonotus obliquus sclerotia (Chaga) consist mainly of hispidin analogs and melanins, and are thought to be the active constituents to treat several human diseases. In submerged cultures of the fungus, however, no information is currently available on the production of phenolic compounds and their corresponding pharmacological functions. In this study, phenolic compounds from Chaga and submerged cultures of the fungus were assayed for their composition and immune-stimulating effects. Phenolic compounds produced by I. obliquus in submerged cultures mostly consist of flavonoids, together with small amounts of hispidin analogs and melanins. This is quite contrary to the situation in Chaga, where flavonoids are determined as trace elements. Furthermore, phenolic compounds from Chaga show capacity about two-fold higher than those produced in submerged cultures in inhibiting cyclophosphamide-induced reduction of bodyweight, spleen index and viability of peripheral lymphocytes in test mice. Thus less production of hispidin analogs and melanins is likely to be responsible for less immune-stimulating effects in phenolic compounds from submerged cultures, and additional factors should be imposed during submerged cultures of I. obliquus to regulate biosynthesis of phenolic compounds directed to the composition similar to Chaga.展开更多
Objective To optimize the extracting technology of assessing the maximum yield of phenolic compounds (PC) from Inonotus obliquus by single factor experiments and orthogonal array design methods through aqueous two-pha...Objective To optimize the extracting technology of assessing the maximum yield of phenolic compounds (PC) from Inonotus obliquus by single factor experiments and orthogonal array design methods through aqueous two-phase systems combined with ultrasonic extraction. Methods The range of the independent variables, namely levels of acetone and ammonium sulfate, and ultrasonic time were identified by a first set of single factor experiments. The actual values of the independent variables coded at four levels and three factors were selected based on the results of the single factor experiments. Subsequently, the levels of acetone and ammonium sulfate, and ultrasonic time were optimized using the orthogonal array method. Results The optimum conditions for the extraction of PC were found to use 7.0 mL acetone, 5.5 mg ammonium sulfate, with ultrasonic time for 5 min. Under these optimized conditions, the experimental maximum yield of PC was 37.8 mg/g, much higher than that of the traditional ultrasonic extraction (UE, 29.0 mg/g). And the PC obtained by this method had stronger anti-oxidative activities than those by traditional UE method. Conclusion These results indicate the suitability of the models developed and the success in optimizing the extraction conditions. This is an economical and efficient method for extracting polyphenols from I. obliquus.展开更多
Background and Aims:Hepatitis B virus(HBV)infection has been found to increase hepatocellular sensitivity to carcinogenic xenobiotics,by unknown mechanisms,in the generation of hepatocellular carcinoma.The pregnane X ...Background and Aims:Hepatitis B virus(HBV)infection has been found to increase hepatocellular sensitivity to carcinogenic xenobiotics,by unknown mechanisms,in the generation of hepatocellular carcinoma.The pregnane X receptor(PXR)is a key regulator of the body’s defense against xenobiotics,including xenobiotic carcinogens and clinical drugs.In this study,we aimed to investigate the molecular mechanisms of HBV X protein(HBx)-PXR signaling in the synergistic effects of chemical carcinogens in HBV-associated hepatocarcinogenesis.Methods:The expression profile of PXR-cytochrome p4503A4(CYP3A4)signaling was determined by PCR,western blotting,and tissue microarray.Cell viability and aflatoxin B1(AFB1)cytotoxicity were measured using the cell counting kit-8 assay.Target gene expression was evaluated using transient transfection and real time-PCR.The genotoxicity of AFB1 was assessed in newborn mice with a single dose of AFB1.Results:HBx enhanced the hepatotoxicity of AFB1 by activating CYP3A4 and reducing glutathione Stransferase Mu 1(GSTM1)in cell lines.Activation of PXR by pregnenolone 16α-carbonitrile increased AFB1-induced liver tumor incidence by up-regulating oncogenic KRAS to enhance interleukin(IL)-11:IL-11 receptor subunit alpha-1(IL11RA-1)-mediated inflammation in an HBx transgenic model.Conclusions:Our finding regarding AFB1 toxicity enhancement by an HBx-PXR-CYP3A4/GSTM1-KRASIL11:IL11RA signaling axis provides a rational explanation for the synergistic effects of chemical carcinogens in HBV infection-associated hepatocarcinogenesis.展开更多
基金Supported by Natural Science Foundation of the Education Department of Jiangsu Province (No. 05KJA36012), and Natural Science Foundation of Jiangsu Province (BK2006034)
文摘Lanosterol and ergosterol are the active principles with potential pharmacological activities in Inonotus obliquus. However, the two sterols are less accumulated in cultured mycelia of the fungus. In this study, different carbon and nitrogen sources and pH levels together with three metal ions were assayed for their effects on accumulation of the two sterols in the fungus. Among the tested media the growth medium consisting of glucose (1.5%), rice powder (0.5%), yeast extract (0.4%), wheat bran (0.1%), KH2PO4 (0.01%) and MgSO4·7H2O (0.05%) with pH level at 6.5 yielded a maximum production of the two sterols, which can further be increased following the treatment of Ag+, Cu2+ and Ca2+. Supplementing Ag+ at concentrations of 0.28 and 0.35μmol partially inhibited ergosterol biosynthesis, leading to an enhanced accumulation of lanosterol, the presence of intermediates of ergosterol biosynthetic pathway and a reduced accumulation of ergosterol in cultured mycelia of I.
基金a Grant from Natural Science Foundations of Education Department of Jiangsu Province (No. 05KJA36012)a Grant of Natural Science Foundations from the Government of Jiangsu Province (No. BK2006034)
文摘Phenolic compounds from field-grown Inonotus obliquus sclerotia (Chaga) consist mainly of hispidin analogs and melanins, and are thought to be the active constituents to treat several human diseases. In submerged cultures of the fungus, however, no information is currently available on the production of phenolic compounds and their corresponding pharmacological functions. In this study, phenolic compounds from Chaga and submerged cultures of the fungus were assayed for their composition and immune-stimulating effects. Phenolic compounds produced by I. obliquus in submerged cultures mostly consist of flavonoids, together with small amounts of hispidin analogs and melanins. This is quite contrary to the situation in Chaga, where flavonoids are determined as trace elements. Furthermore, phenolic compounds from Chaga show capacity about two-fold higher than those produced in submerged cultures in inhibiting cyclophosphamide-induced reduction of bodyweight, spleen index and viability of peripheral lymphocytes in test mice. Thus less production of hispidin analogs and melanins is likely to be responsible for less immune-stimulating effects in phenolic compounds from submerged cultures, and additional factors should be imposed during submerged cultures of I. obliquus to regulate biosynthesis of phenolic compounds directed to the composition similar to Chaga.
基金Natural Science Foundation of China (31070052)Natural Science Foundation of Xuzhou Normal University (08XLY14)
文摘Objective To optimize the extracting technology of assessing the maximum yield of phenolic compounds (PC) from Inonotus obliquus by single factor experiments and orthogonal array design methods through aqueous two-phase systems combined with ultrasonic extraction. Methods The range of the independent variables, namely levels of acetone and ammonium sulfate, and ultrasonic time were identified by a first set of single factor experiments. The actual values of the independent variables coded at four levels and three factors were selected based on the results of the single factor experiments. Subsequently, the levels of acetone and ammonium sulfate, and ultrasonic time were optimized using the orthogonal array method. Results The optimum conditions for the extraction of PC were found to use 7.0 mL acetone, 5.5 mg ammonium sulfate, with ultrasonic time for 5 min. Under these optimized conditions, the experimental maximum yield of PC was 37.8 mg/g, much higher than that of the traditional ultrasonic extraction (UE, 29.0 mg/g). And the PC obtained by this method had stronger anti-oxidative activities than those by traditional UE method. Conclusion These results indicate the suitability of the models developed and the success in optimizing the extraction conditions. This is an economical and efficient method for extracting polyphenols from I. obliquus.
基金This study was funded by the National Natural Science Foun-dation of China(Grant Nos.81772972,81672731,81572703,81572451)Natural Science Foundation of Guangdong Prov-ince(Grant Nos.2021A1515010776,2015A030313449)+1 种基金Science and Technology Planning Project of Guangdong Province“Public Research and Capacity Building”Special Project Fund(Grant No.2014A020212285)Department of Education,Guangdong Government under the Toptier University Development Scheme for Research and Control of Infectious Diseases(Grant Nos.2016026,2015060,2015089).
文摘Background and Aims:Hepatitis B virus(HBV)infection has been found to increase hepatocellular sensitivity to carcinogenic xenobiotics,by unknown mechanisms,in the generation of hepatocellular carcinoma.The pregnane X receptor(PXR)is a key regulator of the body’s defense against xenobiotics,including xenobiotic carcinogens and clinical drugs.In this study,we aimed to investigate the molecular mechanisms of HBV X protein(HBx)-PXR signaling in the synergistic effects of chemical carcinogens in HBV-associated hepatocarcinogenesis.Methods:The expression profile of PXR-cytochrome p4503A4(CYP3A4)signaling was determined by PCR,western blotting,and tissue microarray.Cell viability and aflatoxin B1(AFB1)cytotoxicity were measured using the cell counting kit-8 assay.Target gene expression was evaluated using transient transfection and real time-PCR.The genotoxicity of AFB1 was assessed in newborn mice with a single dose of AFB1.Results:HBx enhanced the hepatotoxicity of AFB1 by activating CYP3A4 and reducing glutathione Stransferase Mu 1(GSTM1)in cell lines.Activation of PXR by pregnenolone 16α-carbonitrile increased AFB1-induced liver tumor incidence by up-regulating oncogenic KRAS to enhance interleukin(IL)-11:IL-11 receptor subunit alpha-1(IL11RA-1)-mediated inflammation in an HBx transgenic model.Conclusions:Our finding regarding AFB1 toxicity enhancement by an HBx-PXR-CYP3A4/GSTM1-KRASIL11:IL11RA signaling axis provides a rational explanation for the synergistic effects of chemical carcinogens in HBV infection-associated hepatocarcinogenesis.