沈郁強（Shen, Yuh-Chiang）

沈郁強實驗組合照

姓名：沈郁強（Shen, Yuh-Chiang）
職稱：研究員兼中醫藥臨床研究組組長
電話：2820 -1999 轉 9101、9121
E-mail : yuhcs@nricm.edu.tw

學歷:
國立陽明大學 藥理學研究所 博士

主要經歷:
國立中國醫藥研究所 中醫基礎醫學組 研究員
國立中國醫藥研究所 中醫基礎醫學組 副研究員
國立中國醫藥研究所 中醫基礎醫學組 助理研究員
國立台北護理健康大學 護理系兼任教授 (部定)
台北醫學大學中草藥學程 兼任副教授
國立中國醫藥研究所 博士後研究員
國家衛生研究院 癌症研究組 博士後研究員
臺灣大學醫學院附設醫院藥劑部高考二級薦任公職藥師

專長:
創新中醫藥（iTCM）之系統性轉譯研究與多標靶治療策略，聚焦於將複雜疾病重新定義為動態網絡狀態（dynamic network states）與吸引子（attractor）轉換問題，並解析中風與神經退化疾病之神經保護機轉。專長涵蓋發炎與免疫調控（TLR、JAK/STAT、PI3K/AKT、NETosis）、白血球與細胞分子生物學，整合多體學（multi-omics）、動物模型與真實世界數據（RWD），建構跨尺度之臨床轉譯平台與系統醫學模型。

研究簡介:

現代醫學深受以分子層級為核心的還原論拆解系統（reductionism）所主導，將疾病視為離散分子異常的結果，並依賴單一靶點進行治療。此一框架雖在急性與機制明確的疾病中帶來革命性突破，卻難以充分解釋與有效治療如COVID-19、慢性發炎性疾病與神經退化疾病等複雜病症。愈來愈多證據顯示，這些疾病並非源於單一缺陷，而是跨越多層級生物網絡之整體重組與失衡。我們在此提出一個整合性的系統醫學框架，將疾病重新概念化為一種動態網絡狀態（dynamic network state），其穩定存在於涵蓋免疫、神經與代謝系統之病理吸引子（attractor）結構中。在此觀點下，疾病進程不再被視為線性分子事件的連鎖反應，而是不同穩定狀態之間的轉換；治療效果亦非來自單一節點的抑制，而是透過調控網絡拓撲結構，驅動系統跨越臨界點，回歸健康狀態。此一新範式為多組分治療策略提供了機制基礎，包括中醫藥在內，其低劑量、分散式的作用可誘導系統層級的重組，進而恢復生理性吸引子。透過以「吸引子動態（attractor dynamics）」重新詮釋疾病與治療，我們建立了一座連結還原論生物學與整體醫學的理論橋樑，並為複雜人類疾病的理解、預測與調控開啟全新方向。

沈研究員長期致力於創新中醫藥（iTCM）與中藥現代化，並提出「Evidence Chain（證據鏈）」結合本所智財中心「CMCTC（Clinical-driven Modernization of Chinese Traditional Medicine）」轉譯模式，建立從臨床觀察（bedside）、機制驗證（bench）到真實世界應用（real-world）的循環式轉譯研究框架。其研究突破傳統「單一病因－單一靶點」之線性醫學觀，提出「疾病作為動態狀態（disease as a dynamic state）」之系統醫學觀點，將複雜疾病理解為多層級生物網絡（神經、免疫、代謝）中的穩定吸引子（attractor states）；在此架構下，疾病並非單一分子異常，而是系統落入病理吸引子，治療亦非單點消除，而是透過跨越臨界轉換（critical state transition）引導系統回歸健康吸引子。於COVID-19疫情期間，其主導開發清冠一號（NRICM101）與清冠二號（NRICM102），結合多體學、RNA-Seq與動物模型，證實中藥複方透過多組分協同調控（multi-component synergy）與網絡重塑（network reconfiguration），調節關鍵發炎與免疫路徑（TLR、JAK/STAT、PI3K/AKT、NETosis），推動系統由疾病吸引子轉移至健康吸引子，顯著降低重症與死亡風險。在機制層面，其進一步提出複雜疾病本質為跨網絡臨界轉換問題，並以多標靶（multi-target）、網絡調控（network regulation）與吸引子重塑（attractor modulation）為核心策略，結合AI與網絡藥理學，闡明中藥複方在低濃度條件下透過湧現（emergence）與系統重組產生整體療效之機制。

團隊建立整合性轉譯平台，涵蓋中藥設計、品質控制（CMC/HPLC）、機制研究、動物模型與臨床及真實世界數據（RWD），形成可重現之轉譯生態系，並透過propensity score matching等方法，將RWD提升至近似RCT等級之證據；同時提出以「系統狀態轉移」作為臨床療效評估之新指標（beyond single biomarkers）。其研究進一步顯示，不同疾病可共享發炎與神經網絡失衡之核心機制，並對應至相似之病理吸引子結構，從而建立跨疾病可複製之轉譯模式。沈郁強研究員於2020至2025年間五度入選史丹佛大學全球前2%頂尖科學家名單，其研究不僅深化中醫藥的科學基礎，更以「吸引子動態（attractor dynamics）」為核心，建立融合東方醫學與現代系統科學之新醫學框架，開創兼具臨床價值、產業影響力與國際競爭力之典範。
 

期刊論文:限所內研究人員(用Email)點選編輯點此編輯

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

代表著作

  1. Wei WC, Tsai KC, Liaw CC, Chiou CT, Tseng YH, Liao GY, Lin YC, Chiou WF, Liou KT, Yu IS, Shen YC(*), Su YC. NRICM101 ameliorates SARS-CoV-2-S1-induced pulmonary injury in K18-hACE2 mice model. Front Pharmacol. 2023 Jun 21;14:1125414. doi: 10.3389/fphar.2023.1125414. PMID: 37416063; PMCID: PMC10320700. (*), 共同責任作者 (臺灣清冠一號有效治療COVID19研究)
  2. Wei WC, Liaw CC, Tsai KC, Chiou CT, Tseng YH, Chiou WF, Lin YC, Tsai CI, Lin CS, Lin CS, Liou KT, Yu IS, Shen YC(*), Su YC. Targeting spike protein-induced TLR/NET axis by COVID-19 therapeutic NRICM102 ameliorates pulmonary embolism and fibrosis. Pharmacol Res. 2022 Oct;184:106424. doi: 10.1016/j.phrs.2022.106424. Epub 2022 Sep 5. PMID: 36064077; PMCID: PMC9443660. (*),共同責任作者 (臺灣清冠二號有效治療COVID19重症研究)
  3. Chang CC, Wang YH, Yen JC, Liaw CC, Tsai KC, Wei WC, Chiou WF, Chiou CT, Liou KT, Shen YC(*), Su YC. NRICM101 in combatting COVID-19 induced brain fog: Neuroprotective effects and neurovascular integrity preservation in hACE2 mice. J Tradit Complement Med. 2024 Jul 3;15(1):36-50. doi: 10.1016/j.jtcme.2024.07.001. PMID: 39807266; PMCID: PMC11725119. (*), 共同責任作者 (臺灣清冠一號有效治療COVID後腦霧研究)
  4. Shen et al (2024). NRICM102: A Breakthrough in Treating Pulmonary Inflammation, Fibrosis, and COPD – A Multi-Target Approach to Respiratory Health. (臺灣清冠二號有效治療COPD研究; IP application)
  5. Shen et al (2024). Intervention of NRICM102 and N-acetylcysteine in mitigating hepatorenal toxicity and enhancing cellular defense against bongkrekic acid poisoning. (臺灣清冠二號有效治療邦克烈酸誘發肝腎衰竭研究; IP application)
  6. Chern CM, Lu CK, Liou KT, Wang YH, Tsai KC, Chang CL, Chang CC, Shen YC(*). Medicarpin isolated from Radix Hedysari ameliorates brain injury in a murine model of cerebral ischemia. J Food Drug Anal. 2021 Dec 15;29(4):581-605. doi: 10.38212/2224-6614.3377. PMID: 35649147; PMCID: PMC9931010. (*), 責任作者 (臺灣醒腦一號有效治療缺血型中風之研究1)
  7. Wang HW, Liou KT, Lin HJ, Shen YC(*). Deciphering the neuroprotective mechanisms of Bu-yang Huan-wu decoction by an integrative neurofunctional and genomic approach in ischemic stroke mice. J Ethnopharmacol. 2011 Oct 31;138(1):22-33. doi: 10.1016/j.jep.2011.06.033. Epub 2011 Jul 8. PMID: 21784143. (*), 責任作者 (臺灣醒腦一號有效治療缺血型中風之研究2)
  8. Shen YC, Lu CK, Liou KT, Hou YC, Lin YL, Wang YH, Sun HJ, Liao KH, Wang HW. Common and unique mechanisms of Chinese herbal remedies on ischemic stroke mice revealed by transcriptome analyses. J Ethnopharmacol. 2015 Sep 15;173:370-82. doi: 10.1016/j.jep.2015.07.018. Epub 2015 Jul 31. PMID: 26239152. 第一作者 (中藥臨床驗方有效治療缺血型中風研究)
     

專利佈局

  1. 沙巴蛇草之萃取方法、其萃取物以及用於治療骨質疏鬆、神經退化性疾病、骨骼肌萎縮及促進傷口癒合之用途
  2. 治療或預防神經性疾病之藥物 (臺灣醒腦一號)
  3. 植物組成物、中草藥組成物在製備治療肺損傷藥物中之用途(臺灣清冠二號)
  4. 植物組成物、中草藥組成物及其用途 (臺灣清冠二號)
  5. USE OF PLANT COMPOSITION, TRADITIONAL CHINESE MEDICINE COMPOSITION IN PREPARING MEDICINE FOR TREATING COVID-19 (臺灣清冠二號)
  6. PLANT COMPOSITION, TRADITIONAL CHINESE MEDICINE COMPOSITION AND USE THEREOF (臺灣清冠二號)
  7. 牛膝萃取方法、牛膝萃取物、其用途及包含其之藥物組合
  8. A composition of Chinese medicine ingredients for treating neurodegenerative diseases (臺灣清腦一號)
  9. A composition of  food ingredients for use as a preventive, therapeutic, or ameliorating agent for acute central nervous system injuries and resulting sequelae (臺灣醒腦一號)

Publication List (2011-2023)

  1. Liu SH, Huang HT, Lo IW, Lin YC, Liao GY, Chao CH, Huang HC, Chang FR, Li TL, Shen YC*, Liaw CC. Potential natural product 3,4-seco-schitriterpenoids from Kadsura japonica L. as anti-neuroinflammatory agents. Bioorg Chem. 2023 Sep 6;141:106843. doi: 10.1016/j.bioorg.2023.106843. Epub ahead of print. PMID:37696148.
  2. Lin SY, Chang CL, Liou KT, Kao YK, Wang YH, Chang CC, Kuo TBJ, Huang HT, Yang CCH, Liaw CC, Shen YC*. The protective role of Achyranthes aspera extract against cisplatin-induced nephrotoxicity by alleviating oxidative stress, inflammation, and PANoptosis. J Ethnopharmacol. 2023 Aug 28;319(Pt 1):117097. doi: 10.1016/j.jep.2023.117097. Epub ahead of print. PMID: 37648176.
  3. Chang SS, Huang HT, Wei WC, Lo IW, Lin YC, Chao CH, Liao GY, Shen YC, Chen JJ, Li TL, Lin LT, Tai CJ, Kuo YH, Liaw CC. Anti-inflammatory effect of euphane-and tirucallane-type triterpenes isolated from the traditional herb <i>Euphorbia neriifolia</i> L. Front Chem. 2023 Jun 23;11:1223335. doi: 10.3389/fchem.2023.1223335. PMID: 37426336; PMCID: PMC10326319.
  4. Wei WC, Tsai KC, Liaw CC, Chiou CT, Tseng YH, Liao GY, Lin YC, Chiou WF, Liou KT, Yu IS, Shen YC*, Su YC. NRICM101 ameliorates SARS-CoV-2-S1-induced pulmonary injury in K18-hACE2 mice model. Front Pharmacol. 2023 Jun 21;14:1125414. doi:10.3389/fphar.2023.1125414. PMID: 37416063; PMCID: PMC10320700.
  5. Huang HT, Lo IW, Liao GY, Lin YC, Shen YC, Huang HC, Li TL, Lee KT, Kuo YH, Liaw CC. Anti-inflammatory sesquiterpene and triterpene acids from <i>Mesona procumbens</i> Hemsley. Front Chem. 2022 Sep 15;10:1003356. doi: 10.3389/fchem.2022.1003356. PMID: 36186589; PMCID: PMC9520569.
  6. Wei WC, Liaw CC, Tsai KC, Chiou CT, Tseng YH, Chiou WF, Lin YC, Tsai CI, Lin CS, Lin CS, Liou KT, Yu IS, Shen YC*, Su YC. Targeting spike protein-induced TLR/NET axis by COVID-19 therapeutic NRICM102 ameliorates pulmonary embolism and fibrosis. Pharmacol Res. 2022 Oct;184:106424. doi: 10.1016/j.phrs.2022.106424. Epub 2022 Sep 5. PMID: 36064077; PMCID: PMC9443660.
  7. Tseng YH, Lin SJ, Hou SM, Wang CH, Cheng SP, Tseng KY, Lee MY, Lee SM, Huang YC, Lin CJ, Lin CK, Tsai TL, Lin CS, Cheng MH, Fong TS, Tsai CI, Lu YW, Lin JC, Huang YW, Hsu WC, Kuo HH, Wang LH, Liaw CC, Wei WC, Tsai KC, Shen YC, Chiou WF, Lin JG, Su YC. Curbing COVID-19 progression and mortality with traditional Chinese medicine among hospitalized patients with COVID-19: A propensity score-matched analysis. Pharmacol Res. 2022 Oct;184:106412. doi: 10.1016/j.phrs.2022.106412. Epub 2022 Aug 23. PMID: 36007774; PMCID: PMC9395232.
  8. Chern CM, Lu CK, Liou KT, Wang YH, Tsai KC, Chang CL, Chang CC, Shen YC*. Medicarpin isolated from Radix Hedysari ameliorates brain injury in a murine model of cerebral ischemia. J Food Drug Anal. 2021 Dec 15;29(4):581-605. doi: 10.38212/2224-6614.3377. PMID: 35649147; PMCID: PMC9931010.
  9. Chen LL, Lee MH, Chang CL, Liou KT, Liu SH, Chern CM, Chen HI, Shen YC*, Wang YH. Suppression of Inflammatory and Fibrotic Signals by Cinnamon (<i>Cinnamomum cassia</i>) and Cinnamaldehyde in Cyclophosphamide-Induced Overactive Bladder in Mice. Evid Based Complement Alternat Med. 2021 Dec 22;2021:5205759. doi:10.1155/2021/5205759. PMID: 34976095; PMCID: PMC8716214.
  10. Kung YY, Kuo TBJ, Lai CT, Shen YC, Su YC, Yang CCH. Disclosure of suboptimalhealth status through traditional Chinese medicine-based body constitution and pulse patterns. Complement Ther Med. 2021 Jan;56:102607. doi: 10.1016/j.ctim.2020.102607. Epub 2020 Nov 19. PMID: 33220452.
  11. Chen LL, Shen YC, Ke CC, Imtiyaz Z, Chen HI, Chang CH, Lee MH. Efficacy of cinnamon patch treatment for alleviating symptoms of overactive bladder: A,double-blind, randomized, placebo-controlled trial. Phytomedicine. 2021 Jan; 80:153380. doi: 10.1016/j.phymed.2020.153380. Epub 2020 Oct 12. PMID: 33091856.
  12. Chern CM, Zhou H, Wang YH, Chang CL, Chiou WF, Chang WT, Yao CH, Liou KT, Shen YC*. Osthole ameliorates cartilage degradation by downregulation of NF-κB and HIF-2α pathways in an osteoarthritis murine model. Eur J Pharmacol. 2020 Jan15;867:172799. doi: 10.1016/j.ejphar.2019.172799. Epub 2019 Nov 22. PMID:31765607.
  13. Wang YH , Chern CM , Liou KT , Kuo YH , Shen YC* . Ergostatrien-7,9(11),22-trien-3β-ol from Antrodia camphorata ameliorates ischemic stroke brain injury via downregulation of p65NF-κ-B and caspase 3, and activation of Akt/GSK3/catenin-associated neurogenesis. Food Funct. 2019 Aug1;10(8):4725-4738. doi: 10.1039/c9fo00908f. Epub 2019 Jul 15. PMID: 31304955.
  14. Hsu WH, Shen YC, Shiao YJ, Kuo CH, Lu CK, Lin TY, Ku WC, Lin YL. Combined proteomic and metabolomic analyses of cerebrospinal fluid from mice with ischemic stroke reveals the effects of a Buyang Huanwu decoction in neurodegenerative disease. PLoS One. 2019 Jan 15;14(1):e0209184. doi: 10.1371/journal.pone.0209184. PMID: 30645580; PMCID: PMC6333407.
  15. Wang YH, Liou KT, Tsai KC, Liu HK, Yang LM, Chern CM, Shen YC*. GSK-3 inhibition through GLP-1R allosteric activation mediates the neurogenesis promoting effect of P7C3 after cerebral ischemic/reperfusional injury in mice. Toxicol Appl Pharmacol. 2018 Oct 15;357:88-105. doi: 10.1016/j.taap.2018.08.023. Epub 2018 Sep 4. PMID: 30189238.
  16. Shen YC, Juan CW, Lin CS, Chen CC, Chang CL. NEUROPROTECTIVE EFFECT OF <i>TERMINALIA CHEBULA</i> EXTRACTS AND ELLAGIC ACID IN PC12 CELLS. Afr J Tradit Complement Altern Med. 2017 Jun 5;14(4):22-30. doi: 10.21010/ajtcam.v14i4.3. PMID: 28638863; PMCID: PMC5471469.
  17. Huang YL, Shen CC, Shen YC, Chiou WF, Chen CC. Anti-inflammatory and Antiosteoporosis Flavonoids from the Rhizomes of Helminthostachys zeylanica. J  Nat Prod. 2017 Feb 24;80(2):246-253. doi: 10.1021/acs.jnatprod.5b01164. Epub 2017 Feb 7. PMID: 28169537.
  18. Chien MY, Chuang CH, Chern CM, Liou KT, Liu DZ, Hou YC, Shen YC*. Salvianolic acid A alleviates ischemic brain injury through the inhibition of inflammation  and apoptosis and the promotion of neurogenesis in mice. Free Radic Biol Med. 2016 Oct;99:508-519. doi: 10.1016/j.freeradbiomed.2016.09.006. Epub 2016 Sep 5. PMID: 27609227.
  19. Chen HJ, Shen YC*, Shiao YJ, Liou KT, Hsu WH, Hsieh PH, Lee CY, Chen YR, Lin YL. Multiplex Brain Proteomic Analysis Revealed the Molecular Therapeutic Effects of Buyang Huanwu Decoction on Cerebral Ischemic Stroke Mice. PLoS One. 2015 Oct 22;10(10):e0140823. doi: 10.1371/journal.pone.0140823. PMID: 26492191; PMCID: PMC4619651.
  20. Shen YC, Lu CK, Liou KT, Hou YC, Lin YL, Wang YH, Sun HJ, Liao KH, Wang HW. Common and unique mechanisms of Chinese herbal remedies on ischemic stroke mice revealed by transcriptome analyses. J Ethnopharmacol. 2015 Sep 15;173:370-82. doi: 10.1016/j.jep.2015.07.018. Epub 2015 Jul 31. PMID: 26239152.
  21. Wong YK, Chou MK, Shen YC, Wang YH, Yen JC, Chen CF, Lin SK, Liao JF. Preventive effect of baicalein on methamphetamine-induced amnesia in the passive avoidance test in mice. Pharmacology. 2014;93(5-6):278-85. doi: 10.1159/000365008. Epub 2014 Aug 21. PMID: 25170749.
  22. Hou YC, Lu CK, Wang YH, Chern CM, Liou KT, Wang HW, Shen YC*. Unique mechanisms of sheng yu decoction ( shèng yù tang) on ischemic stroke mice revealed by an integrated neurofunctional and transcriptome analysis. J Tradit Complement Med. 2013 Oct;3(4):240-9. doi: 10.4103/2225-4110.119703. PMID: 24716184; PMCID: PMC3925003.
  23. Chern CM, Wang YH, Liou KT, Hou YC, Chen CC, Shen YC*. 2-Methoxystypandrone ameliorates brain function through preserving BBB integrity and promoting neurogenesis in mice with acute ischemic stroke. Biochem Pharmacol. 2014 Feb 1;87(3):502-14. doi: 10.1016/j.bcp.2013.11.018. Epub 2013 Dec 14. PMID: 24342702.
  24. Shen YC, Yen JC, Liou KT. Ameliorative effects of caffeic acid phenethyl ester on an eccentric exercise-induced skeletal muscle injury by down-regulating NF-κb mediated inflammation. Pharmacology. 2013;91(3-4):219-28. doi: 10.1159/000348412. Epub 2013 Apr 3. PMID: 23571777.
  25. Pan MY, Shen YC, Lu CH, Yang SY, Ho TF, Peng YT, Chang CC. Prodigiosin activates endoplasmic reticulum stress cell death pathway in human breast carcinoma cell lines. Toxicol Appl Pharmacol. 2012 Dec 15;265(3):325-34. doi: 10.1016/j.taap.2012.08.034. Epub 2012 Sep 12. PMID: 22982536.
  26. Liao YR, Kuo PC, Liang JW, Shen YC, Wu TS. An efficient total synthesis of a potent anti-inflammatory agent, benzocamphorin F, and its anti-inflammatory activity. Int J Mol Sci. 2012;13(8):10432-10440. doi: 10.3390/ijms130810432. Epub 2012 Aug 21. PMID: 22949872; PMCID: PMC3431870.
  27. Lai JK, Wu HC, Shen YC, Hsieh HY, Yang SY, Chang CC. Krüppel-like factor 4 is involved in cell scattering induced by hepatocyte growth factor. J Cell Sci. 2012 Oct 15;125(Pt 20):4853-64. doi: 10.1242/jcs.108910. Epub 2012 Aug 1. PMID: 22854048.
  28. Chern CM, Liao JF, Wang YH, Shen YC*. Melatonin ameliorates neural function by promoting endogenous neurogenesis through the MT2 melatonin receptor in ischemic-stroke mice. Free Radic Biol Med. 2012 May 1;52(9):1634-47. doi: 10.1016/j.freeradbiomed.2012.01.030. Epub 2012 Feb 10. PMID: 22330064.
  29. 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. 2012 Jan;47(1):97-103. doi: 10.1016/j.ejmech.2011.10.026. Epub 2011 Oct 20. PMID: 22115618.
  30. Hsu JW, Wang SJ, Lin CL, Hsieh WC, Lirng JF, Shen YC, Liao MH, Chou YH. Short term vs. long term test-retest reproducibility of ¹²³I-ADAM for the binding of serotonin transporters in the human brain. Psychiatry Res. 2011 Dec 30;194(3):224-229. doi: 10.1016/j.pscychresns.2011.04.011. Epub 2011 Nov 10.PMID: 22079655.
  31. Chang CC, Wang YH, Chern CM, Liou KT, Hou YC, Peng YT, Shen YC*. Prodigiosin inhibits gp91(phox) and iNOS expression to protect mice against the oxidative/nitrosative brain injury induced by hypoxia-ischemia. Toxicol Appl Pharmacol. 2011 Nov 15;257(1):137-47. doi: 10.1016/j.taap.2011.08.027. Epub 2011Sep 7. PMID: 21925195.
  32. Wang HW, Liou KT, Wang YH, Lu CK, Lin YL, Lee IJ, Huang ST, Tsai YH, Cheng YC, Lin HJ, Shen YC*. Deciphering the neuroprotective mechanisms of Bu-yang Huan-wu decoction by an integrative neurofunctional and genomic approach in ischemic stroke mice. J Ethnopharmacol. 2011 Oct 31;138(1):22-33. doi: 10.1016/j.jep.2011.06.033. Epub 2011 Jul 8. PMID: 21784143.