請用此 Handle URI 來引用此文件:
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/67557
完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 鄭光成 | |
dc.contributor.author | Kai-Di Hsu | en |
dc.contributor.author | 許凱廸 | zh_TW |
dc.date.accessioned | 2021-06-17T01:37:32Z | - |
dc.date.available | 2022-08-02 | |
dc.date.copyright | 2017-08-02 | |
dc.date.issued | 2017 | |
dc.date.submitted | 2017-07-31 | |
dc.identifier.citation | Akbar, R., & Yam, W. K. (2011). Interaction of ganoderic acid on HIV related target: molecular docking studies. Bioinformation, 7(8), 413-417.
Ali, A., Ashraf, Z., Kumar, N., Rafiq, M., Jabeen, F., Park, J. H., . . . Attri, P. (2016). Influence of plasma-activated compounds on melanogenesis and tyrosinase activity. Scientific Reports, 6. doi:ARTN 2177910.1038/srep21779 Ates, G., Doktorova, T. Y., Pauwels, M., & Rogiers, V. (2014). Retrospective analysis of the mutagenicity/genotoxicity data of the cosmetic ingredients present on the Annexes of the Cosmetic EU legislation (200012). Mutagenesis, 29(2), 115-121. doi:10.1093/mutage/get068 Bezerra, M. A., Santelli, R. E., Oliveira, E. P., Villar, L. S., & Escaleira, L. A. (2008). Response surface methodology (RSM) as a tool for optimization in analytical chemistry. Talanta, 76(5), 965-977. doi:10.1016/j.talanta.2008.05.019 Bhosle, S., Ranadive, K., Bapat, G., Garad, S., Deshpande, G., & Vaidya, J. (2010). Taxonomy and diversity of Ganoderma from the western parts of maharashtra (India). Mycosphere, 1(3), 249-262. Bishop, K. S., Kao, C. H. J., Xu, Y. Y., Glucina, M. P., Paterson, R. R. M., & Ferguson, L. R. (2015). From 2000 years of Ganoderma lucidum to recent developments in nutraceuticals. Phytochemistry, 114, 56-65. doi:10.1016/j.phytochem.2015.02.015 Bozena Waszkiewicz-Robak (2013). Spent brewer’s yeast and beta-glucans isolated from them as diet components modifying blood lipid metabolism disturbed by an atherogenic diet. InTech, DOI: 10.5772/51530. Brenner, M., & Hearing, V. J. (2008). The protective role of melanin against UV damage in human skin. Photochemistry and Photobiology, 84(3), 539-549. doi:10.1111/j.1751-1097.2007.00226.x Briggs, J. P. (2002). The zebrafish: A new model organism for integrative physiology. American Journal of Physiology-Regulatory Integrative and Comparative Physiology, 282(1), R3-R9. Camp, E., & Lardelli, M. (2001). Tyrosinase gene expression in zebrafish embryos. Development Genes and Evolution, 211(3), 150-153. doi:DOI 10.1007/s004270000125 Carta, R. (1999). Solubilities of L-cystine, L-tyrosine, L-leucine, and glycine in their water solutions. Journal of Chemical and Engineering Data, 44(3), 563-567. doi:DOI 10.1021/je980225d Chan, G. C. F., Chan, W. K., & Sze, D. M. Y. (2009). The effects of beta-glucan on human immune and cancer cells. Journal of Hematology & Oncology, 2. doi:Artn 2510.1186/1756-8722-2-25 Chang, C. J., Lin, C. S., Lu, C. C., Martel, J., Ko, Y. F., Ojcius, D. M., . . . Lai, H. C. (2015). Ganoderma lucidum reduces obesity in mice by modulating the composition of the gut microbiota. Nature Communications, 6. doi:ARTN 748910.1038/ncomms8489 Chang, T. S. (2009). An updated review of tyrosinase inhibitors. International Journal of Molecular Sciences, 10(6), 2440-2475. doi:10.3390/ijms10062440 Chang, Y. W., & Lu, T. J. (2004). Molecular characterization of polysaccharides in hot-water extracts of Ganoderma lucidum fruiting bodies. Journal of Food and Drug Analysis, 12(1), 59-67. Chanmee, T., Ontong, P., Konno, K., & Itano, N. (2014). Tumor-associated macrophages as major players in the tumor microenvironment. Cancers, 6(3), 1670-1690. doi:10.3390/cancers6031670 Chen, N. H., Liu, J. W., & Zhong, J. J. (2010). Ganoderic acid T inhibits tumor invasion in vitro and in vivo through inhibition of MMP expression. Pharmacological Reports, 62(1), 150-163. Chen, S. D., Li, X. M., Yong, T. Q., Wang, Z. G., Su, J. Y., Jiao, C. W., . . . Yang, B. B. (2017). Cytotoxic lanostane-type triterpenoids from the fruiting bodies of Ganoderma lucidum and their structure-activity relationships. Oncotarget, 8(6), 10071-10084. doi:10.18632/oncotarget.14336 Chen, S. L., Xu, J., Liu, C., Zhu, Y. J., Nelson, D. R., Zhou, S. G., . . . Sun, C. (2012). Genome sequence of the model medicinal mushroom Ganoderma lucidum. Nature Communications, 3. doi:ARTN 91310.1038/ncomms1923 Chen, S. Y., Chang, C. L., Chen, T. H., Chang, Y. W., & Lin, S. B. (2016). Colossolactone H, a new Ganoderma triterpenoid exhibits cytotoxicity and potentiates drug efficacy of gefitinib in lung cancer. Fitoterapia, 114, 81-91. doi:10.1016/j.fitote.2016.08.015 Chen, W. C., Tseng, T. S., Hsiao, N. W., Lin, Y. L., Wen, Z. H., Tsai, C. C., . . . Tsai, K. C. (2015). Discovery of highly potent tyrosinase inhibitor, T1, with significant anti-melanogenesis ability by zebrafish in vivo assay and computational molecular modeling. Scientific Reports, 5. doi:ARTN 799510.1038/srep07995 Chen, Y., Bicker, W. F., Wu, J. Y., Xie, M. Y., & Lindner, W. G. (2012). Simultaneous determination of 16 nucleosides and nucleobases by hydrophilic interaction chromatography and its application to the quality evaluation of Ganoderma. Journal of Agricultural and Food Chemistry, 60(17), 4243-4252. doi:10.1021/jf300076j Cheng, K. C. (2008). Skin color in fish and humans: Impacts on science and society. Zebrafish, 5(4), 237-242. doi:10.1089/zeb.2008.0577 Cheng, K. C., Demirci, A., & Catchmark, J. M. (2010). Effects of plastic composite support and pH profiles on pullulan production in a biofilm reactor. Applied Microbiology and Biotechnology, 86(3), 853-861. doi:DOI 10.1007/s00253-009-2332-x Cheng, K. C., Ren, M., & Ogden, K. L. (2013). Statistical optimization of culture media for growth and lipid production of Chlorella protothecoides UTEX 250. Bioresource Technology, 128, 44-48. doi:10.1016/j.biortech.2012.09.085 Cheng, S., & Sliva, D. (2015). Ganoderma lucidum for cancer treatment: we are close but still not there. Integrative Cancer Therapies, 14(3), 249-257. doi:10.1177/1534735414568721 Cheng, Z. H., & Wu, T. (2013). TLC Bioautography: High throughput technique for screening of bioactive natural products. Combinatorial Chemistry & High Throughput Screening, 16(7), 531-549. Chien, C. C., Tsai, M. L., Chen, C. C., Chang, S. J., & Tseng, C. H. (2008). Effects on tyrosinase activity by the extracts of Ganoderma lucidum and related mushrooms. Mycopathologia, 166(2), 117-120. doi:10.1007/s11046-008-9128-x Choi, T. Y., Kim, J. H., Ko, D. H., Kim, C. H., Hwang, J. S., Ahn, S., . . . Yoon, T. J. (2007). Zebrafish as a new model for phenotype-based screening of melanogenic regulatory compounds. Pigment Cell Research, 20(2), 120-127. doi:10.1111/j.1600-0749.2007.00365.x Deepalakshmi, K., Mirunalini, S., Krishnaveni, M., & Arulmozhi, V. (2013). In vitro and in vivo antioxidant potentials of an ethanolic extract of Ganoderma lucidum in rat mammary carcinogenesis. Chinese Journal of Natural Medicines, 11(6), 621-627. doi:10.3724/Sp.J.1009.2013.00621 Deri, B., Kanteev, M., Goldfeder, M., Lecina, D., Guallar, V., Adir, N., & Fishman, A. (2016). The unravelling of the complex pattern of tyrosinase inhibition. Scientific Reports, 6. doi:ARTN 3499310.1038/srep34993 Di Giouanni, S., Borloz, A., Urbain, A., Marston, A., Hostettmann, K., Carrupt, P. A., & Reist, M. (2008). In vitro screening assays to identify natural or synthetic acetylcholinesterase inhibitors: Thin layer chromatography versus microplate methods. European Journal of Pharmaceutical Sciences, 33(2), 109-119. doi:10.1016/j.ejps.2007.10.004 Ding, H. Y., Chang, T. S., Shen, H. C., & Tai, S. S. K. (2011). Murine tyrosinase Inhibitors from Cynanchum bungei and evaluation of in vitro and in vivo depigmenting activity. Experimental Dermatology, 20(9), 720-724. doi:10.1111/j.1600-0625.2011.01302.x Dondorp, A. M., Nosten, F., Yi, P., Das, D., Phyo, A. P., Tarning, J., . . . White, N. J. (2009). Artemisinin resistance in Plasmodium falciparum malaria. New England Journal of Medicine, 361(5), 455-467. doi:DOI 10.1056/NEJMoa0808859 Elinav, E., Nowarski, R., Thaiss, C. A., Hu, B., Jin, C. C., & Flavell, R. A. (2013). Inflammation-induced cancer: crosstalk between tumours, immune cells and microorganisms. Nature Reviews Cancer, 13(11), 759-771. doi:10.1038/nrc3611 Elmore, S. (2007). Apoptosis: A review of programmed cell death. Toxicologic Pathology, 35(4), 495-516. doi:10.1080/01926230701320337 Fang, Q. H., Tang, Y. J., & Zhong, J. J. (2002). Significance of inoculation density control in production of polysaccharide and ganoderic acid by submerged culture of Ganoderma lucidum. Process Biochemistry, 37(12), 1375-1379. doi:Pii S0032-9592(02)00017-1Doi 10.1016/S0032-9592(02)00017-1 Fang, Q. H., & Zhong, J. J. (2002a). Effect of initial pH on production of ganoderic acid and polysaccharide by submerged fermentation of Ganoderma lucidum. Process Biochemistry, 37(7), 769-774. doi:Doi 10.1016/S0032-9592(01)00278-3 Fang, Q. H., & Zhong, J. J. (2002b). Submerged fermentation of higher fungus Ganoderma lucidum for production of valuable bioactive metabolites-ganoderic acid and polysaccharide. Biochemical Engineering Journal, 10(1), 61-65. doi:Pii S1369-703x(01)00158-9Doi 10.1016/S1369-703x(01)00158-9 Fang, Q. H., & Zhong, J. J. (2002c). Two-stage culture process for improved production of ganoderic acid by liquid fermentation of higher fungus Ganoderma lucidum. Biotechnology Progress, 18(1), 51-54. doi:Doi 10.1021/Bp010136g Feitelson, D. G. (2015). From Repeatability to Reproducibility and Corroboration. SIGOPS Oper. Syst. Rev., 49(1), 3-11. doi:10.1145/2723872.2723875 Fernando, K. M. E. P. (2008). The host preference of a Ganoderma lucidum strain for three tree species of Fabaceae family; Cassia nodosa, Cassia fistula and Delonix regia. Journal of the National Science Foundation of Sri Lanka, 36(4), 323-326. Ferreira, I. C. F. R., Heleno, S. A., Reis, F. S., Stojkovic, D., Queiroz, M. J. R. P., Vasconcelos, M. H., & Sokovic, M. (2015). Chemical features of Ganoderma polysaccharides with antioxidant, antitumor and antimicrobial activities. Phytochemistry, 114, 38-55. doi:10.1016/j.phytochem.2014.10.011 Flemming, H. C., & Wingender, J. (2010). The biofilm matrix. Nature Reviews Microbiology, 8(9), 623-633. doi:10.1038/nrmicro2415 Fraga, I., Coutinho, J., Bezerra, R. M., Dias, A. A., Marques, G., & Nunes, F. M. (2014). Influence of culture medium growth variables on Ganoderma lucidum exopolysaccharides structural features. Carbohydrate Polymers, 111, 936-946. doi:10.1016/j.carbpol.2014.05.047 Gan, K. H., Fann, Y. F., Hsu, S. H., Kuo, K. W., & Lin, C. N. (1998). Mediation of the cytotoxicity of lanostanoids and steroids of Ganoderma tsugae through apoptosis and cell cycle. Journal of Natural Products, 61(4), 485-487. doi:Doi 10.1021/Np9704664 Gao, J. L., Leung, K. S. Y., Wang, Y. T., Lai, C. M., Li, S. P., Hu, L. E., . . . Yu, Z. L. (2007). Qualitative and quantitative analyses of nucleosides and nucleobases in Ganoderma spp. by HPLC-DAD-MS. Journal of Pharmaceutical and Biomedical Analysis, 44(3), 807-811. doi:10.1016/j.jpba.2007.03.012 Gao, Y., Dai, X., Chen, G., Ye, J., & Zhou, S. (2003). A Randomized, Placebo-Controlled, Multicenter Study of Ganoderma lucidum (W.Curt.:Fr.) Lloyd (Aphyllophoromycetideae) Polysaccharides in Patients with Advanced Lung Cancer. 5(4), 14. doi:10.1615/InterJMedicMush.v5.i4.40 Gao, Y., Lan, J., Dai, X., Ye, J., & Zhou, S. (2004). A Phase I/II Study of Ling Zhi Mushroom Ganoderma lucidum (W.Curt.:Fr.) Lloyd (Aphyllophoromycetideae) Extract in Patients with Type II Diabetes Mellitus. 6(1), 8. doi:10.1615/IntJMedMushr.v6.i1.30 Gao, Y., Zhou, S., Chen, G., Dai, X., & Ye, J. (2002). A Phase I/II study of a Ganoderma lucidum (Curt.: Fr.) P. Karst. extract (Ganopoly) in patients with advanced cancer. 4(3), 8. doi:10.1615/IntJMedMushr.v4.i3.30 Gao, Y., Zhou, S., Chen, G., Dai, X., Ye, J., & Gao, H. (2002). A Phase I/II study of a Ganoderma lucidum (Curt.: Fr.) P. Karst. (Ling Zhi, Reishi Mushroom) extract in patients with chronic hepatitis. 4(4), 7.doi:10.1615/IntJMedMushr.v4.i4.50 Gao, Y. H., Zhou, S. F., Jiang, W. Q., Huang, M., & Dai, X. H. (2003). Effects of Ganopoly (R) (A Ganoderma lucidum polysaccharide extract) on the immune functions in advanced-stage cancer patients. Immunological Investigations, 32(3), 201-215. doi:Doi 10.1081/Imm-120022979 Gao, Z., Moore, T., Smith, A. P., Doub, W., Westenberger, B., & Buhse, L. (2007). Gauge repeatability and reproducibility for accessing variability during dissolution testing: A technical note. AAPS PharmSciTech, 8(4), 11-15. doi:10.1208/pt0804082 Garcia, P., & Furlan, R. L. E. (2015). Multiresponse optimisation applied to the development of a TLC autography for the detection of tyrosinase inhibitors. Phytochemical Analysis, 26(4), 287-292. doi:10.1002/pca.2562 Germanas, J. P., Wang, S. G., Miner, A., Hao, W., & Ready, J. M. (2007). Discovery of small-molecule inhibitors of tyrosinase. Bioorganic & Medicinal Chemistry Letters, 17(24), 6871-6875. doi:10.1016/j.bmcl.2007.10.014 Gokce, E. C., Kahveci, R., Atanur, O. M., Gurer, B., Aksoy, N., Gokce, A., . . . Kahveci, O. (2015). Neuroprotective effects of Ganoderma lucidum polysaccharides against traumatic spinal cord injury in rats. Injury-International Journal of the Care of the Injured, 46(11), 2146-2155. doi:10.1016/j.injury.2015.08.017 Grundemann, C., Garcia-Kaufer, M., Sauer, B., Scheer, R., Merdivan, S., Bettin, P., . . . Lindequist, U. (2015). Comparative chemical and biological investigations of beta-glucan-containing products from shiitake mushrooms. Journal of Functional Foods, 18, 692-702. doi:10.1016/j.jff.2015.08.022 Hajjaj, H., Mace, C., Roberts, M., Niederberger, P., & Fay, L. B. (2005). Effect of 26-oxygenosterols from Ganoderma lucidum and their activity as cholesterol synthesis inhibitors. Applied and Environmental Microbiology, 71(7), 3653-3658. doi:Doi 10.1128/Aem.71.7.3653-3658.2005 Hamdan, D., Leboeuf, C., Pereira, C., Jourdan, N., Verneuil, L., Bousquet, G., & Janin, A. (2015). A digestive allergic reaction with hypereosinophilia imputable to docetaxel in a breast cancer patient: a case report. BMC Cancer, 15, 993. doi:10.1186/s12885-015-2008-0 Hashim, S. N. N. S., Schwarz, L. J., Danylec, B., Mitri, K., Yang, Y. Z., Boysen, R. I., & Hearn, M. T. W. (2016). Recovery of ergosterol from the medicinal mushroom, Ganoderma tsugae var. Janniae, with a molecularly imprinted polymer derived from a cleavable monomer-template composite. Journal of Chromatography A, 1468, 1-9. doi:10.1016/j.chroma.2016.09.004 Hassan, A. M. S. (2012). TLC bioautographic method for detecting lipase inhibitors. Phytochemical Analysis, 23(4), 405-407. doi:10.1002/pca.1372 Hitchcock, D. I. (1924). The solubility of tyrosine in acid and in alkali. Journal of General Physiology, 6(6), 747-757. doi:DOI 10.1085/jgp.6.6.747 Hsieh, C., Tseng, M. H., & Liu, C. J. (2006). Production of polysaccharides from Ganoderma lucidum (CCRC 36041) under limitations of nutrients. Enzyme and Microbial Technology, 38(1-2), 109-117. doi:10.1016/j.enzmictec.2005.05.004 Hsin, I. L., Ou, C. C., Wu, M. F., Jan, M. S., Hsiao, Y. M., Lin, C. H., & Ko, J. L. (2015). GMI, an Immunomodulatory Protein from Ganoderma microsporum, potentiates cisplatin-induced apoptosis via autophagy in lung cancer cells. Molecular Pharmaceutics, 12(5), 1534-1543. doi:10.1021/mp500840z Hsu, K. D., Wu, S. P., Lin, S. P., Lum, C. C., & Cheng, K. C. (2017). Enhanced active extracellular polysaccharide production from Ganoderma formosanum using computational modeling. Journal of Food and Drug Analysis, 0(0). doi:10.1016/j.jfda.2016.12.006 Hsu, K. D., Chen, H. J., Wang, C. S., Lum, C. C., Wu, S. P., Lin, S. P., & Cheng, K. C. (2016). Extract of Ganoderma formosanum Mycelium as a highly potent tyrosinase inhibitor. Scientific Reports, 6. doi:ARTN 3285410.1038/srep32854 Hu, S. T., Zheng, Z. P., Zhang, X. C., Chen, F., & Wang, M. F. (2015). Oxyresveratrol and trans-dihydromorin from the twigs of Cudrania tricuspidata as hypopigmenting agents against melanogenesis. Journal of Functional Foods, 13, 375-383. doi:10.1016/j.jff.2015.01.010 Huang, L., Sun, F., Liang, C. Y., He, Y. X., Bao, R., Liu, L. X., & Zhou, C. Z. (2009). Crystal structure of LZ-8 from the medicinal fungus Ganoderma lucidium. Proteins-Structure Function and Bioinformatics, 75(2), 524-527. doi:10.1002/prot.22346 Huang, S. C., Mao, J. X., Ding, K., Zhou, Y., Zeng, X. L., Yang, W. J., . . . Pei, G. (2017). Polysaccharides from Ganoderma lucidum promote cognitive function and neural progenitor proliferation in mouse model of Alzheimer's disease. Stem Cell Reports, 8(1), 84-94. doi:10.1016/j.stemcr.2016.12.007 Iozumi, K., Hoganson, G. E., Pennella, R., Everett, M. A., & Fuller, B. B. (1993). Role of tyrosinase as the determinant of pigmentation in cultured human melanocytes. Journal of Investigative Dermatology, 100(6), 806-811. doi:DOI 10.1111/1523-1747.ep12476630 Jesionek, W., Moricz, A. M., Alberti, A., Ott, P. G., Kocsis, B., Horvath, G., & Choma, I. M. (2015). TLC-direct bioautography as a bioassay guided method for investigation of antibacterial compounds in hypericum perforatum L. Journal of Aoac International, 98(4), 1013-1020. doi:10.5740/jaoacint.14-233 Jo, W. S., Cho, Y. J., Cho, D. H., Park, S. D., Yoo, Y. B., & Seok, S. J. (2009). Culture conditions for the mycelial growth of Ganoderma applanatum. Mycobiology, 37(2), 94-102. Jutti Levita, Keu Heng Chao, & Mutakin. (2014). Interactions of Ganoderiol-F with aspartic proteases of HIV and plasmepsin for anti-HIV and anti-malarial discovery. International Journal of Pharmacy and Pharmaceutical Sciences, 6(5), 561-566. Kalahroudi, V. G., Kamalidehghan, B., Kani, A. A., Aryani, O., Tondar, M., Ahmadipour, F., . . . Houshmand, M. (2014). Two novel tyrosinase (TYR) gene mutations with pathogenic impact on oculocutaneous albinism type 1 (OCA1). Plos One, 9(9). doi:ARTN e10665610.1371/journal.pone.0106656 Kang, D., Mutakin, M., & Levita, J. (2015). Computational study of triterpenoids of Ganoderma lucidum with aspartic protease enzymes for discovering HIV-1 and plasmepsin inhibitors. 2015, 7(1). doi:10.5539/ijc.v7n1p62 Karlsson, J., von Hofsten, J., & Olsson, P. E. (2001). Generating transparent zebrafish: A refined method to improve detection of gene expression during embryonic development. Marine Biotechnology, 3(6), 522-527. doi:DOI 10.1007/s1012601-0053-4 Kawagishi, H., Fukuhara, F., Sazuka, M., Kawashima, A., Mitsubori, T., & Tomita, T. (1993). 5'-deoxy-5'-methylsulphinyladenosine, a platelet-aggregation inhibitor from Ganoderma lucidum. Phytochemistry, 32(2), 239-241. doi:Doi 10.1016/S0031-9422(00)94974-4 Kim, H. M., Park, M. K., & Yun, J. W. (2006). Culture pH affects exopolysaccharide production in submerged mycelial culture of Ganoderma lucidum. Applied Biochemistry and Biotechnology, 134(3), 249-262. doi:Doi 10.1385/Abab:134:3:249 Kim, J. H., Baek, S. H., Kim, D. H., Choi, T. Y., Yoon, T. J., Hwang, J. S., . . . Lee, C. H. (2008). Downregulation of melanin synthesis by haginin A and its application to in vivo lightening model. Journal of Investigative Dermatology, 128(5), 1227-1235. doi:10.1038/sj.jid.5701177 Kim, J. K., Kim, M., Cho, S. G., Kim, M. K., Kim, S. W., & Lim, Y. H. (2010). Biotransformation of mulberroside A from Morus alba results in enhancement of tyrosinase inhibition. Journal of Industrial Microbiology & Biotechnology, 37(6), 631-637. doi:10.1007/s10295-010-0722-9 Klupp, N. L., Kiat, H., Bensoussan, A., Steiner, G. Z., & Chang, D. H. (2016). A double-blind, randomised, placebo-controlled trial of Ganoderma lucidum for the treatment of cardiovascular risk factors of metabolic syndrome. Scientific Reports, 6. doi:ARTN 2954010.1038/srep29540 Lakornwong, W., Kanokmedhakul, K., Kanokmedhakul, S., Kongsaeree, P., Prabpai, S., Sibounnavong, P., & Soytong, K. (2014). Triterpene lactones from cultures of Ganoderma sp. KM01. Journal of Natural Products, 77(7), 1545-1553. doi:10.1021/np400846k Langheinrich, U. (2003). Zebrafish: a new model on the pharmaceutical catwalk. Bioessays, 25(9), 904-912. doi:10.1002/bies.10326 Lee, K. M., Lee, S. Y., & Lee, H. Y. (1999). Bistage control of pH for improving exopolysaccharide production from mycelia of Ganoderma lucidum in an air-lift fermentor. Journal of Bioscience and Bioengineering, 88(6), 646-650. doi:Doi 10.1016/S1389-1723(00)87094-2 Lee, S. J., Chan, T. H., Chen, T. C., Liao, B. K., Hwang, P. P., & Lee, H. (2008). LPA(1) is essential for lymphatic vessel development in zebrafish. Faseb Journal, 22(10), 3706-3715. doi:10.1096/fj.08-106088 Lee, W. Y., Park, Y., Ahn, J. K., Ka, K. H., & Park, S. Y. (2007). Factors influencing the production of endopolysaccharide and exopolysaccharide from Ganoderma applanatum. Enzyme and Microbial Technology, 40(2), 249-254. doi:DOI 10.1016/j.enzmictec.2006.04.009 Li, A. M., Shuai, X. Y., Jia, Z. J., Li, H. Y., Liang, X. B., Su, D. M., & Guo, W. H. (2015). Ganoderma lucidum polysaccharide extract inhibits hepatocellular carcinoma growth by downregulating regulatory T cells accumulation and function by inducing microRNA-125b. Journal of Translational Medicine, 13. doi:ARTN 10010.1186/s12967-015-0465-5 Li, E. K., Tam, L. S., Wong, C. K., Li, W. C., Lam, C. W. K., Wachtel-Galor, S., . . . Tomlinson, B. (2007). Safety and efficacy of Ganoderma lucidum (Lingzhi) and San miao San supplementation in patients with rheumatoid arthritis: A double-blind, randomized, placebo-controlled pilot trial. Arthritis & Rheumatism-Arthritis Care & Research, 57(7), 1143-1150. doi:10.1002/art.22994 Li, J. Q., Zhang, J. H., Chen, H. M., Chen, X. D., Lan, J., & Liu, C. (2013). Complete mitochondrial genome of the medicinal mushroom Ganoderma lucidum. Plos One, 8(8). doi:ARTN e7203810.1371/journal.pone.0072038 Li, J. R., Cheng, C. L., Yang, W. J., Yang, C. R., Ou, Y. C., Wu, M. J., & Ko, J. L. (2014). FIP-gts potentiate autophagic cell death against cisplatin-resistant urothelial cancer cells. Anticancer Research, 34(6), 2973-2983. Liao, S. F., Liang, C. H., Ho, M. Y., Hsu, T. L., Tsai, T. I., Hsieh, Y. S. Y., . . . Wong, C. H. (2013). Immunization of fucose-containing polysaccharides from Reishi mushroom induces antibodies to tumor-associated Globo H-series epitopes. Proceedings of the National Academy of Sciences of the United States of America, 110(34), 13809-13814. doi:DOI 10.1073/pnas.1312457110 Likhitwitayawuid, K., & Sritularak, B. (2001). A new dimeric stilbene with tyrosinase inhibitiory activity from Artocarpus gomezianus. Journal of Natural Products, 64(11), 1457-1459. doi:10.1021/np0101806 Lin, C. C., Yu, Y. L., Shih, C. C., Liu, K. J., Ou, K. L., Hong, L. Z., . . . Chu, C. L. (2011). A novel adjuvant Ling Zhi-8 enhances the efficacy of DNA cancer vaccine by activating dendritic cells. Cancer Immunology Immunotherapy, 60(7), 1019-1027. doi:10.1007/s00262-011-1016-4 Lin, J. M., Lin, C. C., Chen, M. F., Ujiie, T., & Takada, A. (1995). Radical scavenger and antihepatotoxic activity of Ganoderma formosanum, Ganoderma lucidum and Ganoderma neo-japonicum. Journal of Ethnopharmacology, 47(1), 33-41. doi:Doi 10.1016/0378-8741(95)01251-8 Lin, T. Y., & Hsu, H. Y. (2016). Ling Zhi-8 reduces lung cancer mobility and metastasis through disruption of focal adhesion and induction of MDM2-mediated Slug degradation. Cancer Letters, 375(2), 340-348. doi:10.1016/j.canlet.2016.03.018 Liu, C. D., Dunkin, D., Lai, J., Song, Y., Ceballos, C., Benkov, K., & Li, X. M. (2015). Anti-inflammatory Effects of Ganoderma lucidum triterpenoid in human Crohn's disease associated with downregulation of NF-kappa B signaling. Inflammatory Bowel Diseases, 21(8), 1918-1925. doi:10.1097/Mib.0000000000000439 Liu, C. D., Yang, N., Song, Y., Wang, L. X., Zi, J. C., Zhang, S. W., . . . Li, X. M. (2015). Ganoderic acid C-1 isolated from the anti-asthma formula, ASHMI (TM) suppresses TNF-alpha production by mouse macrophages and peripheral blood mononuclear cells from asthma patients. International Immunopharmacology, 27(2), 224-231. doi:10.1016/j.intimp.2015.05.018 Liu, J., Shimizu, K., Konishi, F., Kumamoto, S., & Kondo, R. (2007). The anti-androgen effect of ganoderol B isolated from the fruiting body of Ganoderma lucidum. Bioorganic & Medicinal Chemistry, 15(14), 4966-4972. doi:DOI 10.1016/j.bmc.2007.04.036 Liu, J., Shiono, J., Shimizu, K., Kukita, A., Kukita, T., & Kondo, R. (2009). Ganoderic acid DM: Anti-androgenic osteoclastogenesis inhibitor. Bioorganic & Medicinal Chemistry Letters, 19(8), 2154-2157. doi:10.1016/j.bmcl.2009.02.119 Lv, G. P., Zhao, J., Duan, J. A., Tang, Y. P., & Li, S. P. (2012). Comparison of sterols and fatty acids in two species of Ganoderma. Chemistry Central Journal, 6. doi:Artn 1010.1186/1752-153x-6-10 Madeo, F., Herker, E., Wissing, S., Jungwirth, H., Eisenberg, T., & Frohlich, K. U. (2004). Apoptosis in yeast. Current Opinion in Microbiology, 7(6), 655-660. doi:10.1016/j.mib.2004.10.012 Martinez, F. O., & Gordon, S. (2014). The M1 and M2 paradigm of macrophage activation: time for reassessment. F1000Prime Rep, 6, 13. doi:10.12703/P6-13 Meng, L. Z., Xie, J., Lv, G. P., Hu, D. J., Zhao, J., Duan, J. A., & Li, S. P. (2014). A comparative study on immunomodulatory activity of polysaccharides from two official species of Ganoderma (Lingzhi). Nutrition and Cancer-an International Journal, 66(7), 1124-1131. doi:10.1080/01635581.2014.948215 Mukaiyama, T., Tsujimura, N., Otaka, S., Kosaka, Y., Hata, K., Hori, K., & Sakamoto, K. (2009). Anti-melanogenic activity of ergosterol peroxide from Ganoderma lucidum on a mouse melanoma cell line. In S. Shirahata, K. Ikura, M. Nagao, A. Ichikawa, & K. Teruya (Eds.), Animal Cell Technology: Basic & Applied Aspects (Vol. 15, pp. 273-277): Springer Netherlands. Ohbayashi, N., & Fukuda, M. (2012). Role of Rab family GTPases and their effectors in melanosomal logistics. Journal of Biochemistry, 151(4), 343-351. doi:10.1093/jb/mvs009 Ou, C. C., Hsiao, Y. M., Hou, T. Y., Wu, M. F., & Ko, J. L. (2015). Fungal immunomodulatory proteins alleviate docetaxel-induced adverse effects. Journal of Functional Foods, 19, 451-463. doi:10.1016/j.jff.2015.09.042 Pandey, S., Sree, A., Dash, S. S., & Sethi, D. P. (2013). A novel method for screening beta-glucosidase inhibitors. Bmc Microbiology, 13. doi:Artn 5510.1186/1471-2180-13-55 Papinutti, L. (2010). Effects of nutrients, pH and water potential on exopolysaccharides production by a fungal strain belonging to Ganoderma lucidum complex. Bioresource Technology, 101(6), 1941-1946. doi:10.1016/j.biortech.2009.09.076 Park, C. B., & Lee, S. B. Ammonia production from yeast extract and its effect on growth of the hyperthermophilic archaeonSulfolobus solfataricus. Biotechnology and Bioprocess Engineering, 3(2), 115-118. doi:10.1007/bf02932514 Park, C. B., Ryu, D. D. Y., & Lee, S. B. (2003). Inhibitory effect of L-pyroglutamate on extremophiles: correlation with growth temperature and pH. Fems Microbiology Letters, 221(2), 187-190. doi:10.1016/S0378-1097(03)00213-1 Parvez, S., Kang, M. K., Chung, H. S., Cho, C. W., Hong, M. C., Shin, M. K., & Bae, H. (2006). Survey and mechanism of skin depigmenting and lightening agents. Phytotherapy Research, 20(11), 921-934. doi:10.1002/ptr.1954 Peng, L. H., Xu, S. Y., Shan, Y. H., Wei, W., Liu, S., Zhang, C. Z., . . . Gao, J. Q. (2014). Sequential release of salidroside and paeonol from a nanosphere-hydrogel system inhibits ultraviolet B-induced melanogenesis in guinea pig skin. Int J Nanomedicine, 9, 1897-1908. doi:10.2147/IJN.S59290 Peterson, R. T., Link, B. A., Dowling, J. E., & Schreiber, S. L. (2000). Small molecule developmental screens reveal the logic and timing of vertebrate development. Proceedings of the National Academy of Sciences of the United States of America, 97(24), 12965-12969. doi:DOI 10.1073/pnas.97.24.12965 Pi, C. C., Chu, C. L., Lu, C. Y., Zhuang, Y. J., Wang, C. L., Yu, Y. H., . . . Chen, C. J. (2014). Polysaccharides from Ganoderma formosanum function as a Th1 adjuvant and stimulate cytotoxic T cell response in vivo. Vaccine, 32(3), 401-408. doi:DOI 10.1016/j.vaccine.2013.11.027 Postemsky, P. D., Bidegain, M. A., Gonzalez-Matute, R., Figlas, N. D., & Cubitto, M. A. (2017). Pilot-scale bioconversion of rice and sunflower agro-residues into medicinal mushrooms and laccase enzymes through solid-state fermentation with Ganoderma lucidum. Bioresource Technology, 231, 85-93. doi:10.1016/j.biortech.2017.01.064 Ramsden, C. A., & Riley, P. A. (2014). Tyrosinase: The four oxidation states of the active site and their relevance to enzymatic activation, oxidation and inactivation. Bioorganic & Medicinal Chemistry, 22(8), 2388-2395. doi:10.1016/j.bmc.2014.02.048 Russell, R., & Paterson, M. (2006). Ganoderma - A therapeutic fungal biofactory. Phytochemistry, 67(18), 1985-2001. doi:DOI 10.1016/j.phytochem.2006.07.004 Scholz, S. (2013). Zebrafish embryos as an alternative model for screening of drug-induced organ toxicity. Archives of Toxicology, 87(5), 767-769. doi:10.1007/s00204-013-1044-2 Scholz, S., Sela, E., Blaha, L., Braunbeck, T., Galay-Burgos, M., Garcia-Franco, M., . . . Winter, M. J. (2013). A European perspective on alternatives to animal testing for environmental hazard identification and risk assessment. Regulatory Toxicology and Pharmacology, 67(3), 506-530. doi:10.1016/j.yrtph.2013.10.003 Seo, S. Y., Sharma, V. K., & Sharma, N. (2003). Mushroom tyrosinase: Recent prospects. Journal of Agricultural and Food Chemistry, 51(10), 2837-2853. doi:10.1021/jf020826f Shi, L. A., Ren, A., Mu, D. S., & Zhao, M. W. (2010). Current progress in the study on biosynthesis and regulation of ganoderic acids. Applied Microbiology and Biotechnology, 88(6), 1243-1251. doi:10.1007/s00253-010-2871-1 Shimizu, A., Yano, T., Saito, Y., & Inada, Y. (1985). Isolation of an Inhibitor of Platelet-Aggregation from a Fungus, Ganoderma lucidum. Chemical & Pharmaceutical Bulletin, 33(7), 3012-3015. Shin, J. T., & Fishman, M. C. (2002). From zebrafish to human: Modular medical models. Annual Review of Genomics and Human Genetics, 3, 311-340. doi:10.1146/annurev.genom.3.031402.131506 Siegrist, W., & Eberle, A. N. (1986). In situ melanin assay for MSH using mouse B16 melanoma cells in culture. Analytical Biochemistry, 159(1), 191-197. doi:http://dx.doi.org/10.1016/0003-2697(86)90327-1 Singhania, R. R., Sukumaran, R. K., Patel, A. K., Larroche, C., & Pandey, A. (2010). Advancement and comparative profiles in the production technologies using solid-state and submerged fermentation for microbial cellulases. Enzyme and Microbial Technology, 46(7), 541-549. doi:10.1016/j.enzmictec.2010.03.010 Slominski, A., Tobin, D. J., Shibahara, S., & Wortsman, J. (2004). Melanin pigmentation in mammalian skin and its hormonal regulation. Physiological Reviews, 84(4), 1155-1228. doi:10.1152/physrev.00044.2003 Straub, K. L., Benz, M., & Schink, B. (2001). Iron metabolism in anoxic environments at near neutral pH. Fems Microbiology Ecology, 34(3), 181-186. doi:DOI 10.1111/j.1574-6941.2001.tb00768.x Sun, L. X., Lin, Z. B., Lu, J., Li, W. D., Niu, Y. D., Sun, Y., . . . Duan, X. S. (2017). The improvement of M1 polarization in macrophages by glycopeptide derived from Ganoderma lucidum. Immunol Res, 65(3), 658-665. doi:10.1007/s12026-017-8893-3 Sung, J. H., Park, S. H., Seo, D. H., Lee, J. H., Hong, S. W., & Hong, S. S. (2009). Antioxidative and skin-whitening effect of an aqueous extract of Salicornia herbacea. Bioscience Biotechnology and Biochemistry, 73(3), 552-556. doi:10.1271/bbb.80601 Tai, S. S. K., Lin, C. G., Wu, M. H., & Chang, T. S. (2009). Evaluation of depigmenting activity by 8-hydroxydaidzein in mouse B16 melanoma cells and human volunteers. International Journal of Molecular Sciences, 10(10), 4257-4266. doi:10.3390/ijms10104257 Tan, N. Z., Gao, L., Xu, C., Yang, J. Y., Zhang, Y., Zhao, C. S., . . . Zhu, J. S. (2014). Ganoderma lucidum ReishiMax restored aging-related changes in expressions of multiple gene pathways in normal aging mice. Faseb Journal, 28(1). Tang, Y. J., Zhang, W., Liu, R. S., Zhu, L. W., & Zhong, J. J. (2011). Scale-up study on the fed-batch fermentation of Ganoderma lucidum for the hyperproduction of ganoderic acid and Ganoderma polysaccharides. Process Bioche | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/67557 | - |
dc.description.abstract | 臺灣紫芝為臺灣特有種靈芝,約30年前在桃園地區的楓香樹上首次被發現。由於其新穎性,僅有少數研究證明其藥理潛力,目前研究較詳盡的為臺灣紫芝胞外多醣體的免疫調節與抗腫瘤活性。然而,臺灣紫芝胞外多醣體的液態深層醱酵之最適化生產條件尚未確立,且臺灣紫芝的潛在生理活性仍然未知。
本研究的主要目的為探討臺灣紫芝新穎之活性與增進其胞外多醣體之產量,方向分為三大部份: (1) 研究臺灣紫芝菌絲體萃取物之美白活性 (2) 開發一種結合酪胺酸酶與薄膜層析法的高通量美白藥物篩選平台,以利鑑定臺灣紫芝萃取物的美白活性成份 (3) 利用統計與數學模型,最適化生產臺灣紫芝胞外多醣體的液態培養條件。 臺灣紫芝菌絲體酒精萃取物之乙酸乙酯份化層 (GFE-EA) 相較於其它份化層具有最好的體外抑制酪胺酸酶活性,進一步在B16-F10細胞模式中也發現,GFE-EA透過抑制酪胺酸酶活性與其蛋白表現量的機制,來降低胞泌與胞內黑色素形成。進一步在斑馬魚模式中,發現GFE-EA僅需七份之一麴酸的劑量,便能達到同樣程度的抗黑色素形成效果,且具較低的副作用。以上結果顯示,GFE-EA作為化妝品應用的高度潛力。 為了分離純化GFE-EA中具有美白活性之成分,我們建立了一種酪胺酸酶薄膜層析平台,以利鑑定GFE-EA份化層中的活性組成。再者,此平台賦予研究人員同時進行活性分析與鑑定活性物質之可能。相較以酪胺酸酶活性分析比色法偵測麴酸,酪胺酸酶薄膜層析平台不僅具備較優越的藥物劑量偵測極限,也兼具較低的酵素使用量。此外,Gage R&R分析的結果顯示,此平台具可靠的重複性與再現性。因此,我們利用此平台,從數個GFE-EA份化層中篩選出兩個具抑制酪胺酸活性的份化層 (GFE-EA F4、F5)。值得注意的是,這兩個份化層在斑馬魚模式中同樣顯示抗黑色素形成的效果,證實酪胺酸酶薄膜層析平台在篩選抗黑色素形成之藥物的應用性。 在最適化胞外多醣體的生產部份。我們利用反應曲面法探討起始pH值、葡萄糖與酵母萃取物對於胞外多醣生產的影響,實行Box-Behnken design (BBD) 模型的三因子三階層分析後,發現最佳培養的條件為起始pH值5.3、葡萄糖 49.2克/每公升與酵母萃取物4.9克/每公升。利用此最適化生產條件,經九天的醱酵後,胞外多醣體的總產量達到833毫克/每公升,是使用未優化培養基的1.4倍產量,同時也是目前文獻報導中最高的產量紀錄。特別的是,被認為是多醣體活性來源的β-葡聚醣,在此胞外多醣體中的比例為53 ± 5.5%,顯示臺灣紫芝胞外多醣體擁有免疫調節活性之高度潛力。 以上研究不僅推翻一般認為菌絲體缺乏子實體才擁有特定活性的認知,同時也建立一個優越的酵素薄膜層析平台,使研究者能同時評估混合物樣品的活性與鑑定其活性成份。此外,這是首個闡明最適化臺灣紫芝多醣體生產條件的研究,提供未來大規劃工業化醱酵的基礎。總結來說,我們認為臺灣紫芝的活性代謝物,份別具有作為美白活性化妝品與免疫調節保健食品的潛力。 | zh_TW |
dc.description.abstract | Ganoderma formosanum, an endemic Ganoderma (Lingzhi) species in Taiwan, was firstly identified from Formosan sweet gum (Liquidambar formosana) in Taoyuan County, Taiwan three decades ago. Currently, only few studies had demonstrated its pharmacological potential due to its novelty, among which the immune-modulation and anti-tumor effects of extracellular polysaccharide (EPS) is the most understood. However, optimization for the production of G. formosanum EPS in submerged fermentation has not yet been explored, and potential bioactivities of G. formosanum remain unknown.
The specific aim of this study is to explore the frontiers of bioactivity possessed by G. formosanum and to ameliorate the yield of EPS. The present research is divided into three parts as follows: first, depigmenting activity of G. formosanum mycelium extract was studied rather than Lingzhi’s traditional uses. Second, a high-throughput tyrosinase-based TLC bioautography was developed to identify active ingredients responsible for anti-melanogenic activity of G. formosanum mycelium extract. Third, a collection of statistical and mathematical approaches was used to optimize the medium composition for EPS production in submerged fermentation. To screen depigmenting ingredients from G. formosanum, ethyl acetate fraction of G. formosanum mycelium ethanolic extract (GFE-EA) was demonstrated that exhibits the highest inhibitory activity toward cell-free tyrosinase compared with other fractions. Furthermore, the level of secreted and intracellular melanin of B16-F10 cells were reduced by GFE-EA through suppression of tyrosinase activity and its protein expression. Moreover, GFE-EA exerts similar depigmenting efficacy to kojic acid with lower dosage (approximately one-seventh of dose), but shows less adverse effect to zebrafish. It would appear that GFE-EA has great potential for application in the cosmetics industry. In order to purify and to isolate active compound(s) responsible for anti-melanogenic property of GFE-EA, we established a tyrosinase-based thin layer chromatography (TLC) to identify bioactive ingredients from fractions of GFE-EA, and this technique enable researchers to identify active compound(s) during functional assay. Compared with colorimetric tyrosinase activity assay, tyrosinase-based TLC not only showed better detection limit for kojic acid but also cost lower usage of enzyme. In addition, results of Gage R&R study indicated the repeatability and reproducibility of this platform are reliable. Accordingly, this platform was employed to screen fractions of GFE-EA exerting tyrosinase inhibitory activity, and two fractions (GFE-EA F4, F5) were obtained. Above all, it is worth noting that these fractions also showed depigmenting activity on zebrafish, verifying the applicability of tyrosinase-based TLC for anti-melanogenic drug screening. For optimization of EPS production, response surface methodology (RSM) was employed to study the effects of initial pH, glucose and yeast extract concentration on EPS yield. The optimum medium composition was found to be at initial pH 5.3, 49.2 g/L of glucose and 4.9 g/L of yeast extract by implementing a three-factor-three-level Box-Behnken design (BBD). After a 9-day fermentation with optimal conditions, the yield of EPS reached 833 mg/L, which is 1.4 fold-higher than that from basic medium, and it is the highest yield have been reported to date. Above all, the percentage of β-glucan, a well-recognized bioactive polysaccharide, in EPS was 53 ± 5.5%, suggesting G. formosanum EPS may possess potential immunomodulation activity. Altogether, these results not only subvert the general notion that mycelium lacks certain bioactivities, such as depigmenting activity, possessed by fruit bodies, but also provide a superior enzyme-based TLC platform to enable researchers to conduct functional assay and identify active compound(s) from tested mixture simultaneously. Furthermore, this is also the first research to optimize the culture conditions for G. formosanum EPS production, providing fundamental basis for industrial large-scale fermentation. In this study we argue that metabolites of G. formosanum may possess skin lightening and immunomodulation potential to be a cosmetic and nutraceutical, respectively. | en |
dc.description.provenance | Made available in DSpace on 2021-06-17T01:37:32Z (GMT). No. of bitstreams: 1 ntu-106-D02642005-1.pdf: 3521842 bytes, checksum: 2955e8d1cef27ef5868a29e6c19cedc9 (MD5) Previous issue date: 2017 | en |
dc.description.tableofcontents | TABLE of CONTENTS Page
口試委員會審定書 ii 致謝 iii 摘要 v ABSTRACT vii LIST of FIGURES xiii LIST of TABLES xv CHAPTER 1. INTRODUCTION 1 CHAPTER 2. LITERATURE REVIEW 3 2.1 General Outline 3 2.2 Ganoderma morphological stages and metabolites 4 2.2.1 Comparison of Ganodoerma fruiting body and mycelia 4 2.2.2 Bioactive metabolites produced by Ganoderma 5 2.2.3 Polysaccharide 6 2.2.4 Ganoderic acid (triterpenoid) 7 2.2.5 Immunomodulatory protein 8 2.2.6 Ganoderol, ergosterol, and nucleoside 8 2.3 Novel bioactivities of Ganoderma 9 2.3.1 Anti-tumor activity 11 2.3.2 Alleviation of chemotherapy adverse effects 12 2.3.3 Inflammatory and immune modulation effects 12 2.3.4 Skin lightening 13 2.3.5 Obesity management 13 2.3.6 Neuroprotective effects 14 2.3.7 Anti-viral activity (EV, Flu, and HIV) 14 2.3.8 Anti-malaria activity 15 2.4.1 Inoculation density 16 2.4.2 Initial pH and bi-stage pH 17 2.4.3 Nitrogen limitation 18 2.4.4 Two stage cultivation 19 2.4.5 Oxygen supply 19 2.4.6 Water potential 20 2.4.7 Induction of apoptosis 20 2.4.8 Genetic engineering 21 2.5 Clinical trials of Ganoderma 22 2.5.1 Ongoing clinical trials of Ganoderma drugs 23 CHAPTER 3. EXTRACT OF Ganoderma formosanum as a HIGH POTENT TYROSINASE INHIBITOR. 26 3.1 Abstract 26 3.2 Introduction 27 3.3 Materials and methods 30 3.3.1 Submerged mycelial culture of G. formosanum 30 3.3.2 Preparation of crude extracts from G. formosanum 30 3.3.3 Determination of cell-free tyrosinase inhibitory activity 30 3.3.4 Cell culture 30 3.3.5 Cell viability assay 31 3.3.6 Measurement of melanin content 31 3.3.7 Determination of cellular tyrosinase activity 31 3.3.8 Western blotting analysis 32 3.3.9 Origin and maintenance of zebrafish 32 3.3.10 Phenotype-based evaluation of zebrafish 32 3.3.11 Tyrosinase activity and melanin contents of zebrafish 33 3.3.12 Determination of melanogenic inhibitors effects on heart rate 33 3.3.13 Statistical analysis 33 3.4 Results 35 3.4.1 Inhibitory effects of G. formosanum extracts on cell-free tyrosinase activity 35 3.4.2 Effects of GFE-EA on cell viability 35 3.4.3 GFE-EA exerts anti-melanogenesis effects on B16-F10 melanoma cells 38 3.4.4 Effects of GFE-EA on melanin synthesis and tyrosinase activity in zebrafish 39 3.4.5 Toxicity assay of GFE-EA in zebrafish 43 3.5 Discussion 46 3.6 Conclusion 49 CHAPTER 4. SEEING IS BELIEVEING: A HIGH-THROUGHPUT TYROSINASE-BASED TLC AUTOGRAPHY for ANTI-MELANOGENIC DRUG SCREENING. 50 4.1 Abstract 50 4.2 Introduction 51 4.3 Materials and methods 53 4.3.1 Preparation of L-tyrosine, L-DOPA and tyrosinase stock solution 53 4.3.2 Tyrosinase-based TLC assay procedure 53 4.3.3 Image quantification 53 4.3.4 Repeatability and reproducibility 53 4.3.5 Preparation of Ganoderma formosanum mycelial extracts 53 4.3.6 Tyrosinase-based TLC assay for G. formosanum mycelial extracts 54 4.3.7 Zebrafish embryos maintenance 54 4.3.8 Phenotype-based evaluation of zebrafish embryos 54 4.3.9 Determination of relative melanin contents of zebrafish embryos 55 4.3.10 Statistical analysis 55 4.4 Results 56 4.4.1 Efficacy comparison of L-tyrosine and L-DOPA for tyrosinase-based TLC bioautography 56 4.4.2 Optimization of L-DOPA and tyrosinase amounts for tyrosinase-based TLC 56 4.4.3 A comparison of tyrosinase-based TLC with colorimetric tyrosinase assay on detection limit for kojic acid 56 4.4.4 Repeatability and reproducibility of tyrosinase-based TLC 58 4.4.5 Applicability of tyrosinase-based TLC to screen tyrosinase inhibitor from crude herbal mushroom extracts 62 4.6 Conclusion 69 CHAPTER 5. ENHANCED ACTIVE EXTRACELLULAR POLYSACCHARIDE PRODUCTION from Ganoderma formosanum USING COMPUTATIONAL MODELING. 70 5.1 Abstract 70 5.2 Introduction 71 5.3 Materials and methods 73 5.3.1 Fungal strain and fermentation 73 5.3.3 Effects of carbon, nitrogen and pH levels (experimental design) 74 5.3.4 Measurement of morphology 75 5.3.5 Analysis of β-glucan 75 5.3.6 Monosaccharide composition 75 5.4 Results 77 5.4.1 Response model fitting and adequacy checking 77 5.4.2 Effects of factors on EPS production 79 5.4.3 The relationship of between morphology and EPS yield. 80 5.4.5 The content of β-glucan and monosaccharide composition in EPS 81 5.5 Discussion 83 5.6 Conclusion 86 CHAPTER 6. CONCLUSION and FUTURE PRESPECTIVE 87 REFERENCES 93 LIST of FIGURES Figure 2. 1 (a) Fruiting body of G. sinense and (b) mycelia of G. formosanum. 5 Figure 2. 2 Chemical structure of (a) β-1,3-glucan and (b) ganoderic acid A and S. 7 Figure 3. 1 Effects of GFE-EA on melanogenesis in B16-F10 melanoma cells. 37 Figure 3. 2 Cytotoxicity effect of GFE-EA on HaCaT cells. 38 Figure 3. 3 GFE-EA inhibits tyrosinase activity and attenuates the protein level of tyrosinase in B16-F10 melanoma cells. 40 Figure 3. 4 Depigmenting effect of GFE-EA and melanogenic regulators on melanogenesis of zebrafish in an in vivo phenotype-based system. 41 Figure 3. 5. Inhibitory effect of GFE-EA and melanogenic regulators on the melanin and tyrosinase activity in zebrafish. 42 Figure 3. 6. Effects of GFE-EA and melanogenic regulators on the mortality and heart rate in zebrafish. 44 Figure 4. 1 Efficacy comparison of L-tyrosine and L-DOPA for tyrosinase-based TLC bioautography after a 10-minutes reaction (amount of tyrosinase was 2 units per spot). 57 Figure 4. 2 Optimization of L-DOPA and tyrosinase amount for tyrosinase-based TLC bioautography. Reactions were conducted with 0.5 μg kojic acid to evaluate suitable substrate and enzyme amount for this assay. 58 Figure 4. 3 A comparison of (a) tyrosinase-based TLC bioautography and (b) colorimetric tyrosinase activity assay. 59 Figure 4. 4 Gage R&R Nested study of Tyrosinase-based TLC. 61 Figure 4. 5 Tyrosinase-based TLC bioautography was employed to screen potential tyrosinase inhibitors from G. formosanum extracts. 63 Figure 4. 6 Depigmenting effect of GFE-EA fractions on zebrafish embryos. 64 Figure 4. 7 The influence of hydrochloric acid (0.01N) on tyrosinase activity with and without pH adjustment for tyrosinase. 65 Figure 4. 8 Inhibitory effects of G. formosanum ethanolic extracts (GFE) on tyrosinase activity. E= ethanolic extract of G. formosanum, H=Hexane fraction of GFE, EA=ethyl acetate fraction of GFE, B=Butanol fraction of GFE, W=Water fraction of GFE. 67 Figure 5. 1 Three-dimensional surface and contour plots of three factors on EPS production. 79 Figure 5. 2 Effect of initial pH and medium composition on the morphology of mycelial pellets. 80 Figure 6. 1 Total ion chromatogram (a) and UV spectra (b) of GFE-EA and G. formosanum mycelia ethanolic extract for ganoderic acid analysis 88 Figure 6. 2 Dried mycelia of G. formosanum produced by 500-L industrial bioreactor. 89 Figure 6. 3 Full-scan mass spectrum of GFE-EA fractions. 90 Figure 6. 4 Effect of G. formosanum EPS on lung tumor-bearing C57BL/6J mice. 92 LIST of TABLES Table 2. 1 Comparison of Ganoderma fruiting bodies and mycelia 5 Table 2. 2 Major bioactive components of Ganoderma species 6 Table 2. 3 Bioactivities of Ganodoerma metabolites reported in the past 5 years (2013-2017) 10 Table 2. 4 Strategies for Ganoderma metabolites production in submerged fermentation. 17 Table 2. 5 Ongoing clinical trial of Ganoderma drugs. 25 Table 3. 1 Inhibitory effects of ethanolic extract of G. formosanum and its solvent soluble fractions on cell-free tyrosinase. 35 Table 4. 1 Analysis of variance of tyrosinase-based TLC assay conducted by different operators. 62 Table 4. 2 Gage R&R Nested analysis of tyrosinase-based TLC assay conducted by different operators. 62 Table 5. 1 Levels of factors chosen for the Box-Behnken design. 73 Table 5. 2 Box-Behnken design matrix and experimental results of EPS production, biomass accumulation and final pH. 74 Table 5. 3 Carbon and nitrogen sources selection for G. formosanum EPS production. 77 Table 5. 4 Analysis of variance (ANOVA) for response surface quadratic model. 78 Table 5. 5 Comparison of basic and optimum medium on EPS production. 81 Table 5. 6 Monosaccharide composition of EPS from basic and optimum medium. 82 | |
dc.language.iso | en | |
dc.title | 臺灣紫芝活性代謝物之最適化生產與活性探討 | zh_TW |
dc.title | Optimized Production and Functional Evaluation of Bioactive Metabolites from Ganoderma formosanum | en |
dc.type | Thesis | |
dc.date.schoolyear | 105-2 | |
dc.description.degree | 博士 | |
dc.contributor.oralexamcommittee | 沈偉強,陳宏彰,劉啟德,劉?睿 | |
dc.subject.keyword | 臺灣紫芝,美白活性,酪胺酸?薄膜層析平台,美白藥物篩選,胞外多醣體,β-葡聚醣, | zh_TW |
dc.subject.keyword | Ganoderma formosanum,depigmenting activity,tyrosinase-based TLC bioautography,anti-melanogenic drug screening,EPS,β-glucan., | en |
dc.relation.page | 112 | |
dc.identifier.doi | 10.6342/NTU201702288 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2017-07-31 | |
dc.contributor.author-college | 生物資源暨農學院 | zh_TW |
dc.contributor.author-dept | 生物科技研究所 | zh_TW |
顯示於系所單位: | 生物科技研究所 |
文件中的檔案:
檔案 | 大小 | 格式 | |
---|---|---|---|
ntu-106-1.pdf 目前未授權公開取用 | 3.44 MB | Adobe PDF |
系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。