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Research Fellow/Chief/Shen, Yuh-Chiang

Current position:Research Fellow/Chief, Division of Clinical Chinese Medicine沈郁強實驗組合照
E-mail:yuhcs@nricm.edu.tw

 

Education:Ph.D., Institute of Pharmacology, National Yang-Ming University

 

Major Professional Experiences

1. Research Fellow, Basic Chinese Medicine, National Research Institute of Chinese Medicine 
2. Associate Research Fellow, Basic Chinese Medicine, National Research Institute of Chinese Medicine 
3. Assistant Research Fellow, Basic Chinese Medicine, National Research Institute of Chinese Medicine 
4. Associate Professor, Institute of Biomedical Science, National Chung-hsing University 
5. Adjunct Assistant Professor, General Education Center, National Taipei University of Nursing and Health Science 
6. Post Doctoral Fellow, Basic and Clinic Research, National Research Institute of Chinese Medicine 
7. Post Doctoral Fellow, Division of Cancer Research, National Health Research Institute 
8. Clinic Pharmacist, Department of Pharmacy, National Taiwan University Hospital 

 

Specialty
Elucidating anti-stroke drugs and mechanisms by traditional Chinese medicines (TCM), Leukocyte Cell and Molecular Biology, Inflammation Mechanism and Neuron Protection

 

Research Description
     Ischemic stroke is one of the leading causes of human death in the world. No effective and safe drug is available so far. Growing evidence shows that many experienced traditional Chinese herbal (TCM) remedies are neuroprotective and relative safe for ischemic stroke but lacking bio-oriented evaluation of these multiple ingredients in molecular, cellular and animal levels. The aim of our lab is to determine whether treatment of experienced traditional Chinese herbal remedies could effectively protect brain damage in an ischemic stroke animal model. As one of the classic TCM formula, Bu-yang Huan-wu Decoction 補陽還五湯 (BHD) has been used for improving neurological functional recovery in stroke-induced disability in China for more than 300 years and is the most famous and popular TCM formula clinically used for treating stroke-induced disability in Taiwan. Using an integrative neurofunctional and genomic approach in ischemic stroke mice, we found that BHD is able to protect mice against ischemic stroke and extend lifespan primarily through a significant modification of at least 377 out of 2431 genes that involved in inflammation, apoptosis, angiogenesis and blood coagulation, as well as in mediating neurogenesis and nervous system development. Our unpublished result also showed that there are at least 21 active components in BHD extract including paeoniflorin and many active components; We found oral administration of BHD (0.5-1.0 g/kg) twice daily starting from 2 h immediately after ischemia improved neuronal function by PET, dramatically reduced free radical production by IVIS live-imaging and diminished inflammatory marker gp91phox; BHD also showed BBB protective effect by preserving BBB structure protein occludin to prevent leakage of small molecule RhITC for amelioration of ischemic stroke induced brain injury. Using doublecortin (DCX) and ki67 as two markers for neurogenesis/proliferation study, we found BHD also enhanced cell proliferation and production of neural progenitor within the peri-infarct areas as well as SVZ and DGZ of the stroke mice. BHD achieves this effect majorly by enhancing angiogenesis for BBB remodeling, stimulating endogenous neurogenesis, migration and differentiation/maturation of neural progenitor/neuroblast via targeting many key molecules including GSK-3, Wnt/ b-catenin and Notch/NICD/Hes1.

 

Published Papers

NCBI PubMed :  Yuh-Chiang Shen (Please click!!)
 

  1. Shen, Y.-C., Lu, C.-K., Liou, K.-T., Hou, Y.-C., Lin, Y.-L., Wang, Y.-H., . . . Wang, H.-W. (2015). Common and unique mechanisms of Chinese herbal remedies on ischemic stroke mice revealed by transcriptome analyses. Journal of Ethnopharmacology. doi:10.1016/j.jep.2015.07.018.

  2. Chern, C.-M., Wang, Y.-H., Liou, K.-T., Hou, Y.-C., Chen, C.-C., & Shen, Y.-C. (2014). 2-Methoxystypandrone ameliorates brain function through preserving BBB integrity and promoting neurogenesis in mice with acute ischemic stroke. Biochemical Pharmacology, 87(3), 502-514. doi: 10.1016/j.bcp.2013.11.018

  3. Wong, Y. K., Chou, M. K., Shen, Y. C., Wang, Y. H., Yen, J. C., Chen, C. F., . . . Liao, J. F. (2014). Preventive effect of baicalein on methamphetamine-induced amnesia in the passive avoidance test in mice. Pharmacology, 93(5-6), 278-285. doi:10.1159/000365008

  4. Chang, C. L., Chen, H. S., Shen, Y. C., Lai, G. H., Lin, P. K., & Wang, C. M. (2013). Phytochemical composition, antioxidant activity and neuroprotective effect of Crataegus pinnatifida fruit. South African Journal of Botany, 88, 432-437. doi:10.1016/j.sajb.2013.08.017

  5. Hou, Y.-C., Lu, C.-K., Wang, Y.-H., Chern, C.-M., Liou, K.-T., Wang, H.-W., & Shen, Y.-C. (2013). Unique mechanisms of sheng yu decoction (聖愈湯 Shèng Yù Tang) on ischemic stroke mice revealed by an integrated neurofunctional and transcriptome analysis. Journal of Traditional and Complementary Medicine, 3(4), 240-249. doi:10.4103/2225-4110.119703

  6. Liao JF, She YC, Huang YT, Chen CF. Pharmacology of Polysaccharide from Ginseng Species. International J Biomedical and Pharmaceutical Sciences, 2013, in press

  7. Shen, Y.-C., Yen, J.-C., & Liou K.-T. (2013). Ameliorative effects of caffeic acid phenethyl ester on an eccentric exercise-induced skeletal muscle injury by down-regulating NF-κB mediated inflammation. Pharmacology, 91(3-4), 219-228. doi:10.1159/000348412

  8. Chen, H.-J., Shen, Y.-C., Lin, C.-Y., Tsai, K.-C., Lu, C.-K., Shen, C.-C., & Lin, Y.-L. (2012). Metabolomics study of Buyang Huanwu Tang Decoction in ischemic stroke mice by 1H NMR. Metabolomics, 8(5), 974-984. doi:10.1007/s11306-011-0394-0

  9. Chern, C.-M., Liao, J.-F., Wang, Y.-H., & Shen, Y.-C. (2012). Melatonin ameliorates neural function by promoting endogenous neurogenesis through the MT2 melatonin receptor in ischemic-stroke mice. Free Radical Biology & Medicine, 52(9), 1634-1647. doi:10.1016/j.freeradbiomed.2012.01.030

  10. Lai, J.-K., Wu, H.-C., Shen, Y.-C., Hsieh, H.-Y., Yang, S.-Y., & Chang, C.-C. (2012). Krüppel-like factor 4 is involved in cell scattering induced by hepatocyte growth factor. Journal of Cell Science, 125, 4853-4864. doi:10.1242/jcs.108910

  11. Liao, Y.-R., Kuo, P.-C., Liang, J.-W., Shen, Y.-C., & Wu, T.-S. (2012). An efficient total synthesis of a potent anti-inflammatory agent, benzocamphorin f, and its anti-inflammatory activity. International Journal of Molecular Sciences, 13(8), 10432-10440. doi:10.3390/ijms130810432

  12. Pan, M.-Y., Shen, Y.-C., Lu, C.-H., Yang, S.-Y., Ho, T.-F., Peng, Y.-T., & Chang, C.-C. (2012). Prodigiosin activates endoplasmic reticulum stress cell death pathway in human breast carcinoma cell lines. Toxicology and Applied Pharmacology, 265(3), 325-334. doi:10.1016/j.taap.2012.08.034

  13. Reddy, M. V. B., Shen, Y.-C., Ohkoshi, E., Kenneth, F. B., Qian, K., Lee, K.-H., & Wu, T.-S. (2012). Bis-chalcone analogues as potent NO production inhibitors and as cytotoxic agents. European Journal of Medicinal Chemistry, 47(1), 97-103. doi:10.1016/j.ejmech.2011.10.026

  14. Vijaya Bhaskar Reddy M†, Shen YC†, Ohkoshi E, Bastow KF, Qian K, Lee KH, Wu TS. Bis-chalcone analogues as potent NO production inhibitors and as cytotoxic agents. Eur J Med Chem, 47(1):97-103, 2012. (†equal first author; IF = 3.5, Chemistry, Medicinal 13/59=22%)

  15. Chang, C.-C., Wang, Y.-H., Chern, C.-M., Liou, K.-T., Hou, Y.-C., Peng, Y.-T., & Shen, Y.-C. (2011). Prodigiosin inhibits gp91phox and iNOS expression to protect mice against the oxidative/nitrosative brain injury induced by hypoxia–ischemia. Toxicology and Applied Pharmacology, 257(1), 137-147. doi:10.1016/j.taap.2011.08.027

  16. Chern, C.-M., Liou, K.-T., Wang, Y.-H., Liao, J.-F., Yen, J.-C., & Shen, Y.-C. (2011). Andrographolide inhibits PI3K/AKT-dependent NOX2 and iNOS expression protecting mice against hypoxia/ischemia-induced oxidative brain injury. Planta Medica, 77(15), 1669-1679. doi:10.1055/s-0030-1271019

  17. Hsu, J.-W., Wang, S.-J., Lin, C.-L., Hsieh, W.-C., Lirng, J.-F., Shen, Y.-C., . . . Chou, Y.-H. (2011). Short term vs. long term test–retest reproducibility of 123I-ADAM for the binding of serotonin transporters in the human brain. Psychiatry Research : Neuroimaging, 194(3), 224-229. doi:10.1016/j.pscychresns.2011.04.011

  18. Huang, N.-K., Lin, J.-H., Lin, J.-T., Lin, C.-I., Liu, E. M., Lin, C.-J., . . . Chern, Y. (2011). A new drug design targeting the adenosinergic system for Huntington's disease. PLoS One, 6(6). doi:10.1371/journal.pone.0020934

  19. Reddy, M. V. B., Shen, Y.-C., Yang, J.-S., Hwang, T.-L., Kenneth, F. B., Qian, K., . . . Wu, T.-S. (2011). New bichalcone analogs as NF-κB inhibitors and as cytotoxic agents inducing Fas/CD95-dependent apoptosis. Bioorganic & Medicinal Chemistry, 19(6), 1895-1906. doi:10.1016/j.bmc.2011.02.004

  20. Shi, L.-S., Chao, C.-H., Shen, D.-Y., Chan, H.-H., Chen, C.-H., Liao, Y.-R., . . . Lee, K.-H. (2011). Biologically active constituents from the fruiting body of Taiwanofungus camphoratus. Bioorganic & Medicinal Chemistry, 19(1), 677-683. doi:10.1016/j.bmc.2010.10.032

  21. Thang, T. D., Kuo, P.-C., Yu, C.-S., Shen, Y.-C., Thanh, T. V., Kuo, Y.-H., . . . Wu, T.-S. (2011). Chemical constituents of the leaves of Glochidion obliquum and their bioactivity. Archives of Pharmacal Research, 34(3), 383-389. doi:10.1007/s12272-011-0305-y

  22. Wang, H.-W., Liou, K.-T., Wang, Y.-H., Lu, C.-K., Lin, Y.-L., Lee, I. J., . . . Shen, Y.-C. (2011). Deciphering the neuroprotective mechanisms of Bu-yang Huan-wu decoction by an integrative neurofunctional and genomic approach in ischemic stroke mice. Journal of Ethnopharmacology, 138(1), 22-33. doi:10.1016/j.jep.2011.06.033

  23. Yen, D. H. T., Chen, L.-C., Shen, Y.-C., Chiu, Y.-C., Ho, I. C., Lou, Y.-J., . . . Yen, J.-C. (2011). Protein kinase A-dependent neuronal nitric oxide synthase activation mediates the enhancement of baroreflex response by adrenomedullin in the nucleus tractus solitarii of rats. Journal of Biomedical Science, 18:32. doi:10.1186/1423-0127-18-32

  24. Wu SJ, Leu YL, Chen CH, Chao CH, Shen DY, Chan HH, Lee EJ, Wu TS†, Wang YH, Shen YC†, Qian K, Bastow KF, Lee KH. Camphoratins A-J, potent cytotoxic and anti-inflammatory triterpenoids from the fruiting body of Taiwanofungus camphoratus. J Nat Prod, 73(11):1756-62, 2010. (equal corresponding author) (IF = 3.29, Integrated & Complimentary medicine, 29/197=15 %)

  25. Hou YC, Liou KT, Chern CM, Wang YH, Liao JF, Chang S, Chou YH and Shen YC* Preventive effect of silymarin in cerebral ischemia-reperfusion induced brain injury in the rats, Phytomedicine 2010; 17: 963-73. (corresponding author) (IF = 2.972, Integrated & Complimentary medicine, 2/22=9%)

  26. Chan YY, Li CH, Shen YC, Wu TS. Anti-inflammatory principles from the stem and root barks of Citrus medica. Chem Pharm Bull (Tokyo), 58(1):61-5, 2010. (IF = 1.56, Chemistry, Multidisciplinary, 67/152=44%)

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