中藥分子藥理研究室

中醫分子藥理研究室
Molecular Pharmacology Laboratory of Chinese Medicine

 

主持人：李宗諺 教授

　　　　國立陽明大學 傳統醫藥學研究所博士

聯絡電話：03-2118800分機3537

電子郵件：joyamen@mail.cgu.edu.tw

實驗室位置：第二醫學大樓四樓

  研究主題

  • 肝臟學
  • 肥胖與脂肪肝
  • 脂肪肝與免疫耐受性
  • 抗氧化醫學
  • 中醫複方保肝機轉研究
  • 能量代謝與老化
  • 結腸炎

研究室特性

  • 著重自發性學習與科研邏輯學推論
  • 以多元面向探究生理病理與醫藥的發展

 

研究室簡介

草本植物或其萃取物作為慢性肝損傷的使用在全世界各地有相當的經驗。我們以分子醫學標的作為研究策略來探討藥用植物對肝纖維化/脂肪性肝炎的調控機制，希望以科學實驗的研究結果發展傳統醫學或草藥在醫學應用的有力證據。以分子機制為探討的重點，找出傳統複方或植物化合物的作用。目前，我們實驗室已建立肝纖維化//脂肪性肝炎的實驗動物研究平台。藉此系統，我們從傳統複方茵陳蒿湯，證明其所具有抗氧化特色對肝纖維化/脂肪性肝炎的明顯作用機制。由於本實驗室主要是著重中草藥對肝纖維化與脂肪肝肝炎等疾病的分子機制探討及發展治療學的應用用。因此透過相關研究，希望能夠發展出對這些疾病的預防或治療的新藥或輔助醫學。加上現在已經建立的數種分析介面，例如對於肝臟組織代謝與分子層面調控的精確探討，都能讓我們的研究更具競爭優勢，並提供相關預防及治療的研究標的作用基礎。

There has been an increasing interest worldwide in the use of herbal medicines in chronic liver injury. Systematic studies on the effect of specific traditional Chinese medicinal herbs on hepatic fibrosis and steatohepatitis are designed to obtain evidence-based scientific knowledge on appropriate use of traditional medicinal decoction. In our lab we have established in vivo hepatic fibrosis/steatohepatitis system in mouse models to carry out both the mechanistic and therapeutic studies. We have successfully demonstrated the use of these systems for evaluating the antioxidant properties of Yin-Chen-Hao-Tang. Currently, studies are in progress to elucidate the detailed molecular mechanisms underlying the anti-inflammatory/immuno-modulating effects of herbal medicines or certain phytocompounds. Our goal is to develop therapeutic approaches to effectively prevent and treat these diseases.

RESEARCH EXPERIENCE

我的研究工作重點是探討缺氧訊號在肝纖維化所扮演的角色，研發中草藥在此機轉的創新治療肝病方法。藉由目前所展出來的檢測操作平台，我們發現缺氧訊號觸發（細胞外基質ECM）形成級聯，導致線粒體功能障礙，使得關鍵的脂質和碳水化合物代謝異常，從而造成肝臟疾病。植基於肝臟疾病缺氧反應的主要角色，我們實驗室目前正在進行實驗來闡明肥胖症中脂肪肝的分子機制。同時，我們還研究了肥胖腸道微生物菌叢在缺氧訊號傳導過程中對膽汁流動的調節作用。我們針對肝纖維化的目標是持續關注線粒體功能障礙，調節缺氧和微生物群的穩定性，希望開發出適當的藥物作為肝臟疾病治療或預防之用。

My Research Focus on Hypoxia signaling in hepatic fibrosis and constructive creates new herbal remedy for liver diseases. Through current assay platform, we found that hypoxia signal triggers an (extracellular matrix, ECM) formation cascade leading to the mitochondria dysfunction and selective pathways of lipid and carbohydrate metabolism abnormity that is the main key of hypoxic response in liver diseases. Based on these findings, our lab is currently conducting experiments to elucidate the molecular mechanism of fatty liver in obesity. We are also investigating the roles of microbiota in regulating bile flow during hypoxia signaling in obese studies. Our aim in the fight against hepatic fibrosis is focus on mitochondrial dysfunction, regulation of hypoxia and microbiota stability.

HONORS AND INVITED SPEECHES

2013. 12th Meeting of the Consortium for Globalization of Chinese Medicine (CGCM) Proteomics approach of active component of Yin-Chen-Hao-Tang on steatohepatitis in leptin deficiency ob/ob mice. (oral presentation)

2014. 49th Annual meeting of the Association for the Study of the Liver (EASL) Ursodeoxycholic acid via regulation of bile acids and mammalian target of rapamycin to improve lipid metabolism disorders with non-alcoholic and alcohol-induced fatty liver disease. Young Investigator Reward

2015. 50th Annual meeting of the Association for the Study of the Liver (EASL) Combine therapy with losartan and YC-1 produces browning phenomenon of white adipose mass in ob/ob mice. Young Investigator Reward

2016. 5th European Immunology & 2nd Innate Immunity and Immune System Diseases Berlin, Germany July 21-23, 2016. Electroacupuncture prevents white adipose tissue inflammation through modulation of hypoxia-1a-dependent pathway in obese animals. (oral presentation)

PUBLICATIONS (Since 2012)

  1. Cheng-Hui Wang, Hsuan-Miao Liu, Zi-Yu Chang, Chung-Hua Hsu, Tzung-Yan Lee. Antioxidants rich herbal formula Ger-Gen-Chyn-Lian-Tang protects lipotoxicity and ameliorates inflammation signaling through regulation of mitochondrial biogenesis and mitophagy in nonalcoholic fatty liver disease mice. Frontiers in Bioscience-Landmark (Landmark Ed). 2022, 27(8):242. (SCI) (I.F.:3.115; R/C= 207/297 in BIOCHEMISTRY & MOLECULAR BIOLOGY)
  2. Geng-Hao Liu, Xin-Cheng Zhuo, Yueh-Hsiang Huang, Hsuan-Miao Liu, Ren-Chin Wu, Chia-Jung Kuo, Ning-Hung Chen, Li-Pang Chuang, Shih-Wei Lin, Yen-Lung Chen, Huang-Yu Yang, Tzung-Yan Lee. Alterations in Gut Microbiota and Upregulations of VPAC2 and Intestinal Tight Junctions Correlate with Anti-Inflammatory Effects of Electroacupuncture in Colitis Mice with Sleep Fragmentation. Biology-Basel. 2022, 11(7), 962. (I.F.: 5.168; R/C= 21/94 in BIOLOGY)
  3. Ching-Chuan Yeh, Hsuan-Miao Liu, Ming-Chung Lee, Yann-Lii Leu, Wei-Han, Chiang, Hen-Hong Chang, Tzung-Yan Lee. Phytochemical-rich herbal formula ATG-125 protects against sucrose-induced gastrocnemius muscle atrophy by rescuing Akt signaling and improving mitochondrial dysfunction in young adult mice. Molecular Medicine Reports. 2022, 25(2): 57. (I.F.: 3.423; R/C= 97/195 in MEDICINE, RESEARCH & EXPERIMENTAL)
  4. Zi-Yu Chang, Hsuan-Miao Liu, Yann-Lii Leu, Chung-Hua Hsu, Tzung-Yan Lee. Modulation of gut microbiota combined with upregulation of intestinal tight junction explains anti-inflammatory effect of Corylin on colitis-associated cancer in mice. International Journal of Molecular Sciences. 2022, 23(5): 2667. (I.F.: 6.208; R/C= 69/296 in BIOCHEMISTRY & MOLECULAR BIOLOGY)
  5. Hsuan-Miao Liu, Cheng-Hui Wang, Zi-Yu Chang, Tse-Hung Huang, Tzung-Yan Lee. Losartan attenuates insulin resistance and regulates browning phenomenon of white adipose tissue in ob/ob Mice. Current Issues in Molecular Biology. 2021, 3(3): 1828-1843. (I.F.: 2.976; R/C= 216/296 in BIOCHEMISTRY & MOLECULAR BIOLOGY)
  6. Cheng-Hui Wang, Hsuan-Miao Liu, Zi-Yu Chang, Tse-Hung Huang, Tzung-Yan Lee. Losartan Prevents Hepatic Steatosis and Macrophage Polarization by Inhibiting HIF-1α in a Murine Model of NAFLD. International Journal of Molecular Sciences. 2021, 22(15): 7841. (I.F.: 6.208; R/C= 69/296 in BIOCHEMISTRY & MOLECULAR BIOLOGY)
  7. Geng-Hao Liu, Hsuan-Miao Liu, Yu-Sheng Chen, Tzung-Yan Lee. Effect of Electroacupuncture in Mice with Dextran Sulfate Sodium-Induced Colitis and the Influence of Gut Microbiota. Evidence-Based Complementary and Alternative Medicine. 2020, 2020: 2087903. (I.F.: 2.650; R/C= 16/30 in INTEGRATIVE & COMPLEMENTARY MEDICINE)
  8. Zi-Yu Chang, Chin-Chang Chen, Hsuan-Miao Liu, Yuan-Chieh Yeh, Tung-Yi Lin, Tzung-Yan Lee, Tse-Hung Huang. Positive Effects of Ger-Gen-Chyn-Lian-Tang on Cholestatic Liver Fibrosis in Bile Duct Ligation-Challenged Mice. International Journal of Molecular Sciences. 2019, 20(17): 4181. (I.F.: 6.208; R/C= 69/296 in BIOCHEMISTRY & MOLECULAR BIOLOGY)
  9. Chen YS, Liu HM, Lee TY. (2019) Ursodeoxycholic acid regulates hepatic energy homeostasis and white adipose tissue macrophages polarization in leptin-deficiency obese mice. Cells. 2019, 8, 253 (4.829, 55/190) (Corresponding author)
  10. Chen YP, Liu YW, Lee D, Qiu JT, Lee TY, Liu SJ. (2019) Biodegradable andrographolide-eluting nanofibrous membranes for the treatment of cervical cancer. Int J Nanomedicine. 9;14:421-429. (4.976, 18/252)
  11. Chen YP, Liu HY, Liu YW, Lee TY, and Shih-Jung Liu. (2019) Determination of Electrospinning Parameters’ Strength in Poly(D,L)-lactide-co-glycolide Micro/Nanofiber Diameter Tailoring. J Nanomater. Article ID 2626085. (2.207, 128/284)
  12. Li TH, Yang YY, Huang CC, Liu CW, Tsai HC, Lin MW, Tsai CY, Huang SF, Wang YW, Lee TY, Huang YH, Hou MC, Lin HC. (2019) Elafibranor interrupts adipose dysfunction-mediated gut and liver injury in mice with alcoholic steatohepatitis. Clin Sci (Lond). 13;133(3):531-544. (5.220, 17/133)
  13. Liu GH, Tsai MY, Chang GJ, Wu CM, Lin SK, Chen YS, Lee TY. (2018) Safety Assessment of the Auto Manipulation Device for Acupuncture in Sprague-Dawley Rats: Preclinical Evaluation of the Prototype. Evid Based Complement Alternat Med. 6;2018:5708393. (Corresponding author) (2.064, 10/27)
  14. Lee TY, Leu YL, Wen CK. (2017) Modulation of HIF-1α and STAT3 signaling contributes to anti-angiogenic effect of YC-1 in mice with liver fibrosis. Oncotarget 8(49):86206-86216. (5.168, 44/217)
  15. Liu HM, Liao JF, Lee TY. (2017) Farnesoid X receptor agonist GW4064 ameliorates lipopolysaccharide-induced ileocolitis through TLR4/MyD88 pathway related mitochondrial dysfunction in mice. Biochem Biophys Res Commun. 490:841-848. (Corresponding author) (2.559, 35/72)
  16. Huang TH, Chen CC, Liu HM, Lee TY, Shieh SH. (2017) Resveratrol Pretreatment Attenuates Concanavalin A-induced Hepatitis through Reverse of Aberration in the Immune Response and Regenerative Capacity in Aged Mice. Sci Rep. 7:2705. (Corresponding author) (4.122, 12/64)
  17. Liu HM, Liao JF, Lee TY. (2018) GW4064 attenuates lipopolysaccharide-induced hepatic inflammation and apoptosis through inhibited toll like receptor 4- mediated p38 mitogen activated protein kinase signal pathway in mice. Int J Mol Med. 41(3):1455-1462 (Corresponding author) (2.784, 65/133)
  18. Chen ST, Lee TY, Tsai TH et al.,(2017) Traditional Chinese medicine Danggui Buxue Tang inhibits  colorectal cancer growth through induction of autophagic cell death. Oncotarget, 8(51): 88563-88574. (5.168, 44/217)
  19. Chen CA, Liu CK, Hsu ML, Chi CW, Ko CC, Chen JS, Lai CT, Chang HH, Lee TY, Lai YL, Chen YJ. (2017) Daphnoretin modulates differentiation and maturation of human dendritic cells through down-regulation of c-Jun N-terminal kinase. Int Immunopharmacol. 51:25-301598-017-02881-z. (3.118, 80/155)
  20. Chang CM, Wu WH, Kuo BI, Lee TY, Liu CY, Chang HH. (2017) Corrigendum to "Using a questionnaire among patient, resident doctor and senior supervisor: Are their answers the same?  Complement Ther Med. 32:115. (2.084, 9/27)
  21. Chen CC, Lee TY, Kwok CF, Hsu YP, Shih KC, Lin YJ, Ho LT. (2017) Using proteomics to discover novel biomarkers for fatty liver development and response to CB1R antagonist treatment in an obese mouse model. Proteomics. 17(1-2) 1600292 (1 of 9). (3.532, 21/79)
  22. Liu CK, Chen CA, Lee TY, Chang HH, Liao HF, Chen YJ. Rice protein prolamin promotes anti-leukemia immunity and inhibits leukemia growth in vivo. Food Chem Toxicol. 2017 Sep 22. pii: S0278-6915(17)30562-8. (3.977, 10/133)
  23. Chen ST, Lee TY, Tsai TH, Lin YC, Lin CP, Shieh HR, Hsu ML, Chi CW, Lee MC, Chang HH, Chen YJ. The Traditional Chinese Medicine DangguiBuxue Tang Sensitizes Colorectal Cancer Cells to Chemoradiotherapy. Molecules. 2016 Dec 6;21(12). pii: E1677. (3.098, 68/171)
  24. Chang HH, Luo SF, Hsue YT, Chang CM, Lee TY, Huang YC, Hsu ML, Chen YJ. Modulation of Endothelial Injury Biomarkers by Traditional Chinese Medicine LC in Systemic Lupus Erythematosus Patients Receiving Standard Treatments. Sci Rep. 2016 Feb 5;6:19622. (4.122, 12/64)
  25. Chen CC, Lee TY, Kwok CF, Hsu YP, Shih KC, Lin YJ, Ho LT. Cannabinoid receptor type 1 mediates high-fat diet-induced insulin resistance by increasing forkhead box O1 activity in a mouse model of obesity. Int J Mol Med. 2016 Mar;37(3):743-54. (2.784, 65/133)
  26. Liao HR, Chien CR, Chen JJ, Lee TY, Lin SZ, Tseng CP. The anti-inflammatory effect of 2-(4-hydroxy-3-prop-2-enyl-phenyl)-4-prop-2-enyl-phenol by targeting Lyn kinase in human neutrophils. Chem Biol Interact. 2015 Jul 5;236:90-101. (3.296, 28/87)
  27. Chen CC, Lee TY, Kwok CF, Hsu YP, Shih KC, Lin YJ, Ho LT. Major urinary protein 1 interacts with cannabinoid receptor type 1 in fatty acid-induced hepatic insulin resistance in a mouse hepatocyte model. Biochem Biophys Res Commun. 2015 May 15;460(4):1063-8. (2.559, 35/72)
  28. Wen CK, Lee TY. Electroacupuncture prevents white adipose tissue inflammation through modulation of hypoxia-inducible factors-1α-dependent pathway in obese mice. BMC Complement Altern Med. 2015 Dec 29;15:452. (Corresponding author) (2.109, 8/27)
  29. Lee PC, Yang YY, Lee WP, Lee KC, Hsieh YC, Lee TY, Lin HC. Comparative portal hypotensive effects as propranolol of vitamin D₃ treatment by decreasing intrahepatic resistance in cirrhotic rats. J Gastroenterol Hepatol. 2015 Mar;30(3):628-37. (3.483, 27/80)
  30. Lee PC, Yang YY, Huang CS, Hsieh SL, Lee KC, Hsieh YC, Lee TY, Lin HC. Concomitant inhibition of oxidative stress and angiogenesis by chronic hydrogen-rich saline and N-acetylcysteine treatments improves systemic, splanchnic and hepatic hemodynamics of cirrhotic rats. Hepatol Res. 2015 May;45(5):578-88. (3.418, 31/80)
  31. Huang TH, Chiu YH, Chan YL, Wang H, Li TL, Liu CY, Yang CT, Lee TY, You JS, Hsu KH, Wu CJ. Antrodia cinnamomea alleviates cisplatin-induced hepatotoxicity and enhances chemo-sensitivity of line-1 lung carcinoma xenografted in BALB/cByJ mice. Oncotarget. 2015 Sep 22;6(28):25741-54. (5.168, 44/217)
  32. Chang CM, Wu WH, Kuo BI, Lee TY, Liu CY, Chang HH. Using a questionnaire among patient, resident doctor and senior supervisor: Are their answers the same? Complement Ther Med. 2014 Apr;22(2):296-303. (2.084, 9/27)
  33. Lee TY, Chang HH, Wen CK, Huang TH, Chang YS. Modulation of thioacetamide-induced hepatic inflammations, angiogenesis and fibrosis by andrographolide in mice. J Ethnopharmacol. 2014 Dec 2;158 Pt A:423-30. (3.115, 4/27)
  34. Yang YY, Hsieh SL, Lee PC, Yeh YC, Lee KC, Hsieh YC, Wang YW, Lee TY, Huang YH, Chan CC, Lin HC. Long-term cannabinoid type 2 receptor agonist therapy decreases bacterial translocation in rats with cirrhosis and ascites. J Hepatol. 2014 Nov;61(5):1004-13. (15.040, 4/80)
  35. Yang YY, Lee PC, Huang YT, Lee WP, Kuo YJ, Lee KC, Hsieh YC, Lee TY, Lin HC. Involvement of the HIF-1α and Wnt/β-catenin pathways in the protective effects of losartan on fatty liver graft with ischaemia/reperfusion injury. Clin Sci (Lond). 2014 Jan;126(2):163-74. (5.220, 17/133)
  36. Chang ZY, Lee TY, Huang TH, Wen CK, Chien RN, Chang HH. Hepatoprotective effects of Ger-Gen-Chyn-Lian-Tang in thioacetamide-induced fibrosis in mice. J Chin Med Assoc. 2014 Jul;77(7):360-6. (Corresponding author) (1.660, 72/155)
  37. Wen CK, Lee TY. Electroacupuncture decreases the leukocyte infiltration to white adipose tissue and attenuates inflammatory response in high fat diet-induced obesity rats. Evid Based Complement Alternat Med. 2014;2014:473978. (Corresponding author) (2.064, 10/27)
  38. Liu CY, Wu WH, Huang TP, Lee TY, Chang HH. A novel model for exploring the correlation between patterns and prescriptions in clinical practice of traditional Chinese medicine for systemic lupus erythematosus. Complement Ther Med. 2014 Jun;22(3):481-8. (2.084, 9/27)
  39. Yang YY, Huang YT, Lee TY, Chan CC, Yeh YC, Lee KC, Lin HC. Rho-kinase-dependent pathway mediates the hepatoprotective effects of sorafenib against ischemia/reperfusion liver injury in rats with nonalcoholic steatohepatitis. Liver Transpl. 2012 Nov;18(11):1371-83. (3.756, 8/25)
  40. Kuo JJ, Chang HH, Tsai TH, Lee TY. Curcumin ameliorates mitochondrial dysfunction associated with inhibition of gluconeogenesis in free fatty acid-mediated hepatic lipoapoptosis. Int J Mol Med. 2012 Sep;30(3):643-649. (Corresponding author) (2.784, 65/133)
  41. Kuo JJ, Chang HH, Tsai TH, Lee TY. Positive effect of curcumin on inflammation and mitochondrial dysfunction in obese mice with liver steatosis. Int J Mol Med. 2012 Sep;30(3):673-9. (Corresponding author) (2.784, 65/133)
  42. Yang YY, Tsai TH, Huang YT, Lee TY, Chan CC, Lee KC, Lin HC. Hepatic endothelin-1 and endocannabinoids-dependent effects of hyperleptinemia in nonalcoholic steatohepatitis-cirrhotic rats. Hepatology 2012 May;55(5):1540-50. (14.079, 5/80)
  43. Yang YY, Lee TY, Huang YT, Chan CC, Yeh YC, Lee FY, Lee SD, Lin HC. Asymmetric dimethylarginine (ADMA) determines the improvement of hepatic endothelial dysfunction by vitamin E in cirrhotic rats. Liver Int. 2012 Jan;32(1):48-57. (4.500, 16/80 )

Publications in Chinese

  1. 李宗諺 中醫陰陽循行的量子元素. 中醫學，2017, 6(2), 40-45.
  2. 李宗諺 生命興衰的可能回饋. 中醫學，2017, 6(2), 46-50.
  3. 李宗諺 陰陽觀點的老化修復論. 中醫學，2017, 6(2), 68-75.
  4. 陈怡斌，邱健泰，李宗谚. 艾叶萃取物引发子宫颈癌细胞凋亡的机制探讨. 成都中医药大学学报，2015, 38(1), 17-20
  5. 陳彥融，陳濘宏，李宗諺，張哲慈，林康平，張恒鴻. 阻塞性睡眠呼吸中止症患者之中醫體質與生活品質相關性分析. 中醫藥雜誌，2014, 25(2), 167-175
  6. 周彥廷，楊仕哲，吳文祥，李宗諺，張恒鴻. 腦性麻痹中醫治療之現況探討. 中醫藥雜誌，2013, 24(1): 121-127
  7. 朱元锵，李宗谚，王国辉，陈舜鼎，张恒鸿. 末期肾病血瘀证患者与动脉硬化的关系. 中醫學，2013, 2, 1-6
  8. 周立盛，陳彥融，陳濘宏，李宗諺，黃伯瑜，張恒鴻. 阻塞型睡眠呼吸中止症候群中醫辨證文獻探討. 中醫藥研究論叢，2013, 16 (02), 23-29

GRANDS (Since 2012)

葛根芩連湯對於高脂飲食誘發非酒精性脂肪肝以及法尼醇X受體缺陷致癌鼠肝臟內膽汁酸動態平衡和泛素-蛋白?體系統調控之研究MOST109-2320-B-182-023-MY3 (2020/8/1-2023/7/31).NT$4,000,000.

龍膽瀉肝湯對於法尼醇X受體缺陷致癌鼠肝臟內自噬作用以及腸道微生物菌叢的調控研究. MOST106-2320-B-182-005-MY3 (2017/8/1-2020/7/31). NT$2,734,000.

葛根芩連湯對肝纖維化小鼠肝臟大麻素受體及缺氧誘導因子調控研究MOST103-2320-B-182-002-MY3 (2014/8/1- 2017/7/31). NT$3,300,000.

溫膽湯改善肥胖鼠及糖尿病鼠葡萄糖與脂質代謝的恆定機制研究MOST102-2320-B-182-015-MY3 (2014/8/1- 2016/7/31;). NT$1,960,000.

虎杖對脂質代謝異常的脂肪肝小鼠肝臟法尼酯X受體與膽酸生合成的調控機制MOST102-2320-B-182-014 (2013/8/1- 2014/9/30). NT$950,000.

洋耆草醯胺類化合物對肥胖脂肪肝小鼠肝內mTOR/AKT傳導路徑與脂質異常調控研究MOST101-2320-B-182-017 (2012/8/1- 2013/7/31;). NT$900,000.

蛋白質體學研究薑黃對肥胖、血脂異常、脂肪肝病變小鼠血循內皮前趨細胞與肝臟老化蛋白表現的機制. MOST98-2320-B-182-021-MY3 (2009/8/1- 2012/7/31) NT$2,400,000..

期刊論文編審

  • Liver International
  • Cytokine
  • Journal of Pharmacy and Pharmacology
  • Journal of Medicinal Food
  • Chinese Medicine
  • Method and Findings in Experimental and Clinical Pharmacology
  • British Journal of Pharmacology
  • Journal of Chinese Integrative Medicine
  • Hepatology International
  • Journal of Medicinal Food.
  • European Journal of Gastroenterology & Hepatology 
  • BMC Gastroenterology
  • PLos