選單
現職:
國立陽明交通大學中醫學系教授
Professor, School of Chinese Medicine, NYCU
國立陽明交通大學傳統醫藥研究所 合聘教授
學歷：
美國內布拉斯加州立大學生命科學院 博士
University of Nebraska-Lincoln, Nebraska, USA
School of Biological Sciences (Ph.D.)
美國內布拉斯加州立大學農藝系 碩士
University of Nebraska-Lincoln, Nebraska, USA
Department of Agronomy (Master)
國立臺灣大學 農藝系 學士
National Taiwan University, Taipei, Taiwan.
Department of Agronomy (Bachelor)
經歷：
2010–2024 衛生福利部國家中醫藥研究所 研究員
1995– 2000 國立中國醫藥研究所 副研究員
2002–2024 臺北醫學大學 生藥學系所 兼任副教授
2003–2006 臺灣大學 農藝學研究系所 兼任副教授
學術著作
*Corresponding author
研究計畫-(五年內計畫)
國科會計畫：
I have been interested in polysaccharides production, structure and biological function in fungi. Much of the work I have done in the past used Antrodia cinnamomea as a model for polysaccharide structure and function. For the past five years Dr. Tung-Yi Lin and myself have been working on production, purification, and characterization of sulfated polysaccharides in fungi and how this sulfated polysaccharides responds to anti-cancer and anti-inflammatory activities. My interests in this system is how to use cultured mycelia to provide the opportunity to fine-tune the biosynthetic pathway of sulfated polysaccharide. These polysaccharides from different sources could differ somewhat in structure and composition. Different physicochemical parameters of polysaccharides, such as solubility, primary structure, molecular weight, extent of branching by side-chain substituents, and the charge on the polymer, all appear to influence their biological activities.
Recently, we have also created a series of polysaccharides isolated from Poria cocos, Ganoderma lucidum, Pycnoporus sanguineus, and Rigidoporus ulmarius cultured with different carbon-sourced medium. We have examined the physiological consequence of these cultured mycelia. Sulfated polysaccharide was fully characterized according to its molecular weight distribution and sugar composition. We have observed that different carbon sources generate different polymers with different degrees of polymerization, producing more or less water-soluble may possess higher or lower biological activity. We are in the process of bio-activity assay.
In preparation the bioactive sulfated polysaccharide (SPS) of Antrodia cinnamomea we discovered that a sulfated salt (SO4 2-) could change in the sugar compositions, and degree of sulfation in the SPS. The more the SO4 2-, the higher the sulfation degree. We observed that the degree of sulfation affected the antiangiogenic and neuroprotective properties. These results are consistent with those of Parish et al. who found that the inhibitory activity against human angiogenesis of SPS was critically dependent on the chain length and degree of sulfation. We are continuing to characterize the minimum length of sulfated oligosaccharides with the greatest anti-angiogenic activity by using fragmentation of SPS. In addition, we first demonstrated the existence of lipopolysaccharides (LPS) in medicinal fungus, Antrodia cinnamomea (J. Agri. Food Chem. 2005, 53, 469-474). Chemical and functional properties were investigated on the fungus LPS. Compositional analysis revealed that sorbitol, fucose, galactose and glucose were the neutral sugars in LPS of A. cinnamomea. Compared that with Escherichia coli O129 LPS, galactosamine, glucosamine, galactose, and glucose, were the predominant monosaccharide species in E. coli O129 LPS molecules, whereas galactosamine and glucosamine were absent in A. cinnamomea LPS. Since these properties are different from those of bacterial LPS, the function between fungus and bacterial LPS are also discussed.
We also have Dr. Chia-Chuan Chang to join to elucidate partial structural of fungal polysaccharide by using 1H, 13C and 2D NMR spectroscopy, including NOESY and HMBC experiments for linkage and sequence analysis. We are planning to fractionate and identify the structure of active polysaccharides in anti-cancer and anti-inflammation. Recently, we discovered a novel 2-O sulfated 1,3-/1,4-galactoglucan from cultured mycelia of A. cinnamomea (International Journal of Biological Macromolecules 2023, 241, 124559). By comparing the result of cultured mycelia in the same species but grows in the wield, we may uncover novel function of this species. This work has applied implications for the development of candidates for cancer therapy. Submerged culture may increase the yield potential to achieve the demands of commercial-scale of mycelial and polysaccharide production.
In the past 20 years, major research progress focused on (1) In vitro manipulation of the production of Antrodia cinnamomea and its biological activity. (2) Production of medicinal fungus, Poria cocos, Pycnoporus sanguineus, Armillaria mellea, Fomitopsis pinicola, Rigidoporus ulmarius with biological activities. (3) Precursor-feeding strategy to produce effective compounds of plant. These topics and publications are described as follows.
We first perform a hybrid machine learning approach (ANFIS-NM) to identify the potent factors and optimize the cultivation conditions of A. cinnamomea (Bioresource Technology 2023, 369, 128412; Biomass and Bioenergy 2022, 158, 106349). We investigated the hyphal growth-promoting factors of Antrodia cinnamomea from the host-related species, Cinnamomum camphora (International Journal of Food Microbiology 2006, 106, 32-38). We identified the HGF was in the polysaccharide fraction of C. camphora, and it maximally stimulated growth compared to that of the control.
We demonstrate the biological functions and the underlying mechanisms of sulfated polysaccharides of A. cinnamomea (International Journal of Biological Macromolecules 2023, 241, 124559; International Journal of Biological Macromolecules 2023, 238, 124144; International Journal of Biological Macromolecules 2023, 226, 1236-1247; International Journal of Biological Macromolecules 2021, 170, 307-316; International Journal of Biological Macromolecules 2020, 162, 1476-1483; International Journal of Biological Macromolecules 2020, 159, 1013-1021; International Journal of Biological Macromolecules 2020, 148, 715-721; Carbohydrate Polymers 2019, 216, 204-212; Carbohydrate Polymers 2019, 210, 175-184; Carbohydrate Polymers 2018, 202, 536-544; International Journal of Biological Macromolecules 2018, 120, 952-958; International Journal of Biological Macromolecules 2018, 113, 1198-1205; Carbohydrate Polymers 2017, 167, 229-239; International Journal of Biological Macromolecules 2017, 95, 1144-1152; Food Hydrocolloids 2016, 53, 37-45; Carbohydrate Polymers 2012, 90, 134-139; Carbohydrate Polymers 2011, 83, 545-553; Process Biochemistry 2009, 44, 453-459). We were the first attempt to purify SPS from a fungal species, A. cinnamomea. We determined the physiological nature and chemical architecture of the bioactive domains of the SPS. We prepared series of SPS in our fermentation library of A. cinnamomea. There were significant qualitative changes in the sugar compositions, and degree of sulfation, which influenced their biological activities.
In addition to sulfated polysaccharide, Dr. Nai-Kuei Huang and myself examined the ethanolic extract of A. cinnamomea both in chemical composition and neuroprotection activity. Dr. Huang used a serum deprivation-induced apoptosis in neuronal-like pheochromocytoma (PC12) cells as a cell stress model, and we found that A. cinnamomea was effective in preventing serum-deprived apoptosis according to results of the MTT assay and Hoechst staining. We demonstrated the active component of A. cinnamomea is adenosine (ADO) and the targeting site in this model is A2A-R(Life Sciences 2006, 79, 225-232). A. cinnamomea prevented serum deprivation-induced PC12 cell apoptosis through a PKA-dependent pathway and suppression of JNK and p38 activities (Journal of Agricultural Food Chemistry 2008, 56, 865-74).
Fomitopsis pinicola is another fungus I am interested. It is now being marketed as a tea and food supplement. The fungus is very common on dead trees and plays a very important ecological role in the degradation of woody forest litter. Although the mechanisms underlying the antitumor effects of the extract have still not been clarified, its tumoricidal effects have been confirmed. We found the highest mycelial yield and polysaccharide production change with the time of cultivation. Harvest time selection is also an important factor to obtain maximal fungal production (Process Biochemistry 2008, 43, 829-834). Both polysaccharides and its ethanolic extract were prepared and showed no toxicity to endothelial cells (ECs). Extracted polysaccharides had a strong inhibitory effect on vascular endothelial growth factor (VEGF)-induced tube formation in ECs in a dose-dependent manner. Furthermore, the ethanolic extract dose-dependently suppressed production of the interferon (IFN)-γ-induced inflammation marker, IP-10. These results suggest that different extracts from F. pinicola play different roles in regulating the angiogenic process and inflammation.
I am also working on in vitro production of secondary metabolites in plant cell system. I used precursor-feeding strategy on undifferentiated cell cultures of Solanum lyratum, a medicinal plant, to produceα-solanine, solanidine, and solasodine (Process Biochemistry 2007, 42, 899-903). In this study, S. lyratum cells were fed exogenous plant sterols including cholesterol, stigmasterol, and mixed sterols (β-sitosterol, campesterol, and dihydrobrassicasterol). The maximal solasodine level in cells was 11.19 mg/g dry weight (DW) after 0.05~1 mg/l stigmasterol feeding, which was about tenfold higher than the control. With regard to solanidine levels, the maximal level in cells was 5.84 mg/g DW after feeding with 20 mg/l cholesterol. It is evident that precursor-feeding strategy described above is applicable at least to steroidal alkaloids accumulation in suspension cultures of S. lyratum and could be useful for in vitro production of solasodine and solanidine.
