Browsing by Author "Chang, Shu-Lin"

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Cytopiloyne, a novel polyacetylenic glucoside from Bidens pilosa, functions as a T helper cell modulator
(2007-04-04)
Chiang, Yi-Ming
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Chang, Cicero Lee-Tian
;
Chang, Shu-Lin
;
Yang, Wen-Chin
;
Shyur, Lie-Fen
An extract of Bidens pilosa, an anti-diabetic Asteraceae plant, has recently been reported to modulate T cell differentiation and prevent the development of non-obese diabetes (NOD) in NOD mice. In this paper, a novel bioactive polyacetylenic glucoside, cytopiloyne (1), was identified from the Bidens pilosa extract using ex vivo T cell differentiation assays based on a bioactivity-guided fractionation and isolation procedure. Its structure was elucidated as 2 beta-D-glucopyranosyloxy-1-hydroxytrideca-5,7,9,11-tetrayne by various spectroscopic methods. Functional studies showed that cytopiloyne was able to inhibit the differentiation of naive T helper (Th0) cells into type I T helper (Th1) cells but to promote the differentiation of Th0 cells into type II T helper (Th2) cell. Accordingly, cytopiloyne also suppressed IFN-gamma expression and promoted IL-4 expression in mouse splenocytes ex vivo. These results suggest that cytopiloyne functions as a T cell modulator that may directly contribute to the ethnopharmacological effect of Bidens pilosa extract on preventing diabetes. Moreover, cytopiloyne can serve as an index compound for quality control of lot-to-lot extract preparations of Bidens pilosa. (c) 2006 Elsevier Ireland Ltd. All rights reserved.
Cytopiloyne, a polyacetylenic glucoside, prevents type 1 diabetes in nonobese diabetic mice
(2007-06-01)
Chang, Cicero Lee-Tian
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Chang, Shu-Lin
;
Lee, Yi-Mei
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Chiang, Yi-Ming
;
Chuang, Da-Yung
Some polyacetylenes from the plant Bidens pilosa have been reported to treat diabetes. In this study, we report that the cytopiloyne from B. pilosa, which is structurally different from the above-mentioned polyacetylenes and inhibits CD4(+) T cell proliferation, effectively prevents the development of diabetes in nonobese diabetic mice as evidenced by a normal level of blood glucose and insulin and normal pancreatic islet architecture. Cytopiloyne also suppresses the differentiation of type 1 Th cells but promotes that of type 2 Th cells, which is consistent with it enhancing GATA-3 transcription. Also, long-term application of cytopiloyne significantly decreases the level of CD4(+) T cells inside pancreatic lymph nodes and spleens but does not compromise total Ab responses mediated by T cells. Coculture assays imply that this decrease in CD4(+) T cells involves the Fas ligand/Fas pathway. Overall, our results suggest that cytopiloyne prevents type 1 diabetes mainly via T cell regulation.
Engineering Fungal Nonreducing Polyketide Synthase by Heterologous Expression and Domain Swapping
(2013-02-15)
Yeh, Hsu-Hua
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Chang, Shu-Lin
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Chiang, Yi-Ming
;
Bruno, Kenneth S.
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Oakley, Berl R.
We reannotated the A. niger NR-PKS gene, e_gw1_19.204, and its downstream R domain gene, est_GWPlus_C_190476, as a single gene which we named dtbA. Heterologous expression of dtbA In A. nidulans demonstrated that DtbA protein produces two polyketides, 2,4-dihydroxy-3,5,6-trimethylbenzaldehyde (1) and 6-ethyl-2,4-dihydroxy-3,5-dimethylbenzaldehyde (2). Generation of DtbA Delta R+TE chimeric PKSs by swapping the DtbA R domain with the AusA (austinol biosynthesis) or ANID_06448 TE domain enabled the production of two metabolites with carboxylic acids replacing the corresponding aldehydes.
Flavonoids, centaurein and centaureidin, from Bidens pilosa, stimulate IFN-gamma expression
(2007-06-13)
Chang, Shu-Lin
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Chiang, Yi-Ming
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Chang, Cicero Lee-Tian
;
Yeh, Hsu-Hua
;
Shyur, Lie-Fen
Bidens pilosa is used as an ethnical medicine for bacterial infection or immune modulation in Asia, America and Africa. Here, we employed an IFN-gamma promoter-driven luciferase reporter construct and T cells to characterize immunomodulatory compounds from this plant based on a bioactivity-guided isolation principle. We found that PHA, a positive control, caused a six-fold increase in IFN-gamma promoter activity. In contrast, hot water crude extracts from Bidens pilosa and its butanol subfraction increased IFN-gamma promoter activity to two- and six-fold, respectively. Finally, centaurein (EC50 = 75 mu g/ml) and its aglycone, centaureidin (EC50 = 0.9 mu g/ml), isolated from this butanol subtraction, augmented IFN-gamma promoter activity by similar to four-fold. Consistent with the role of centaurein or its aglycone in IFN-gamma regulation, we showed that centaurein induced the activity of NEAT and NF kappa B enhancers, located within the IFN-gamma promoter, in Jurkat cells. Overall, our results showed that centaurein regulated IFN-gamma transcription, probably via NFAT and NF kappa B in T cells. (c) 2007 Elsevier Ireland Ltd. All rights reserved.
Illuminating the Diversity of Aromatic Polyketide Synthases in Aspergillus nidulans
(2012-05-16)
Ahuja, Manmeet
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Chiang, Yi-Ming
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Chang, Shu-Lin
;
Praseuth, Mike B.
;
Entwistle, Ruth
Genome sequencing has revealed that fungi have the ability to synthesize many more natural products (NPs) than are currently known, but methods for obtaining suitable expression of NPs have been inadequate. We have developed a successful strategy that bypasses normal regulatory mechanisms. By efficient gene targeting, we have replaced, en masse, the promoters of nonreducing polyketide synthase (NR-PKS) genes, key genes in NP biosynthetic pathways, and other genes necessary for NR-PKS product formation or release. This has allowed us to determine the products of eight NR-PKSs of Aspergillus nidulans, including seven novel compounds, as well as the NR-PKS genes required for the synthesis of the toxins alternariol (8) and cichorine (19).
Reconstitution of the early steps of gliotoxin biosynthesis in Aspergillus nidulans reveals the role of the monooxygenase GliC
(2013-04-01)
Chang, Shu-Lin
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Chiang, Yi-Ming
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Yeh, Hsu-Hua
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Wu, Tung-Kung
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Wang, Clay C. C.
The gliotoxin, a member of the epipolythiodioxopiperazine (ETP), has received considerable attention from the scientific community for its wide range of biological activity. Despite the identification of gliotoxin cluster, however, the sequence of steps in the gliotoxin biosynthesis has remained elusive. As an alternative to the gene knock-out and biochemical approaches used so far, here we report using a heterologous expression approach to determine the sequence of the early steps of gliotoxin biosynthesis in Aspergillus nidulans. We identified the GliC, a monooxygenases that involved in the second step of gliotoxin biosynthesis pathway through the catalyzing the hydroxylation at the alpha-position of L-Phe. (C) 2013 Elsevier Ltd. All rights reserved.
The effect of centaurein on interferon-gamma expression and Listeria infection in mice
(2007-02-15)
Chang, Shu-Lin
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Yeh, Hsu-Hua
;
Lin, Yu-Shiun
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Chiang, Yi-Ming
;
Wu, Tung-Kung
We previously found that centaurein enhanced IFN-gamma transcription in T cells. Here, we demonstrate that centaurein increased the IFN-gamma expression in T and NK cells and the serum IFN-gamma level in mice. Centaurein elevated the transcription of T-bet but not GATA-3, which is consistent with its effect on that of IFN-gamma but not IL-4. Additionally, centaurein effectively protected mice against Listeria infection. Moreover, centaurein per se or in combination with antibiotics could treat Listeria infection. Our mechanistic studies suggest that centaurein augments IFN-gamma expression via a transcriptional up-regulation of T-bet and that centaurein protects against or treats Listeria infection via a modulation of IFN-gamma expression. (c) 2006 Elsevier Inc. All rights reserved.