中草藥抗老化功能標的探索研究團隊

主持人：黃聰龍 教授

研究專長：發炎免疫藥理學、分子訊號機轉、藥物研發、天然物藥學

研究團隊成員: 

黃聰龍老師、方嘉佑老師、楊賢鴻醫師、 潘台龍老師、陳金銓老師、呂彥禮老師

蔡永豐醫師、 余黃平醫師、陳俊宇醫師、 高定一醫師

研究架構圖:

研究計畫:

中草藥在現代醫藥的研究和發展上，提供許多寶貴的資訊。中草藥研究團隊的目標在發展中草藥轉譯醫學，並透過中草藥的經驗準則和研究成果來發展新藥。隨著高齡化社會的來臨，老人疾病在近年來已成為迫切解決的問題，因此針對老人疾病的新藥和保健食品開發已經是刻不容緩的議題，而中草藥在這個領域方向提供了一個解決之道。中草藥研究團隊在研究和發展中草藥萃取物和純化物，促進高齡化老年人的身體健康和疾病治療上已經有一定成果也將持續精進。透過酵素、細胞和動物研究以及臨床試驗，詳細建立中草藥萃取物和純化物的藥理學和毒理學知識，並運用MMRC和HARC研究發現的疾病生物指標與危險因子探討與評估中草藥在老年人好發疾病之有效性與專一性。

目標

開發中草藥單方、複方與純化合物應用於老年人好發疾病之保健、預防及治療。

方法

整合團隊人員的學術專長，建立研究平台，系統性進行中草藥研發。

1、化學製備平台：中草藥備制與分析；最適化製程建立；有效成分和指標成分的鑑定。

2、抗老化細胞研究平台：抗發炎；免疫調節；抑制皮膚老化；降低肝臟細胞氧化壓力；酵母菌生命週期；酵素活性。

3、動物疾病實驗模式：肺損傷；肝硬化；光老化皮膚病；牛皮癬；腳掌浮腫發炎；代謝疾病。

主要成果

1.      Lin KH, Tseng YJ, Chen BW, Hwang TL, Chen HY, Dai CF, Sheu JH. Tortuosenes A and B, New Diterpenoid Metabolites from the Formosan Soft Coral Sarcophyton tortuosum. Org Lett. 2014 Mar 7;

       16(5):1314-7.

2.      Lee WR, Shen SC, Chen WY, Aljuffali IA, Suen SY, Fang JY. Noninvasive delivery of siRNA and plasmid DNA into skin by fractional ablation: Erbium:YAG laser versus CO2 laser .Eur J Pharm Biopharm. 2014 Apr;86(3):315-23. 

3.      Lin CH, Aljuffali IA, Fang JY. Lasers as an approach for promoting drug delivery via skin. Expert Opin. Drug Deliv. 2014 Apr;11(4):599-614.

4.      Chen CY, Liaw CC, Chen YH, Chang WY, Chung PJ, Hwang TL*. A novel immunomodulatory effect of ugonin U in human neutrophils via stimulation of phospholipase C. Free Radic Biol Med. 2014 Jul;72:222-31

5.      Hsieh PW, Wen CJ, Yu HP, Aljuffali IA, Huang YH, Fang JY. Nanostructured lipid carriers containing a high percentage of a pluronic copolymer increase the biodistribution of novel PDE4 inhibitors for the treatment of traumatic hemorrhage. J Biomed Nanotechnol.  2014 Aug;10(8):1520-35.

6.      Hwang TL, Aljuffali IA, Lin CF, Chang YT, Fang JY. Cationic additives in nanosystems activate cytotoxicity and inflammatory response of human neutrophils: lipid nanoparticles versus polymeric nanoparticles. Int J Nanomedicine. 2015 Jan 7;10:371-85

7.      Tsai YF, Yu HP, Chang WY, Liu FC, Huang ZC, Hwang TL*. Sirtinol inhibits neutrophil elastase activity and attenuates lipopolysaccharide-mediated acute lung injury in mice. Sci Rep. 2015 Feb 10;5:8347.

8.      Chen CH, Chang CC, Shih TH, Aljuffali IA, Yeh TS, Fang JY.Self-nanoemulsifying drug delivery systems ameliorate the oral delivery of silymarin in rats with Roux-en-Y gastric bypass surgery. International Journal of Nanomedicine,  2015 Mar 25;10:2403-16.

9.      Aljuffali IA, Pan TL, Sung CT, Chang SH, Fang JY. Anti-PDGF receptor β antibody-conjugated squarticles loaded with minoxidil for alopecia treatment by targeting hair follicles and dermal papilla cells.Nanomedicine: Nanotechnology, Biology, and Medicine 2015 Aug;11(6):1321-30.

10.  Hung CF, Chen WY, Hsu CY, Aljuffali IA, Shih HC, Fang JY. Cutaneous penetration of soft nanoparticles via photodamaged skin: Lipid-based and polymer-based nanocarriers for drug delivery. European Journal of Pharmaceutics and Biopharmaceutics. 2015 Aug;94:94-105.

11.  Fang CL, Wen CJ, Aljuffali IA, Sung CT, Huang CL, Fang JY.Passive targeting of phosphatiosomes increases rolipram delivery to the lungs for treatment of acute lung injury: An animal study. Journal of Controlled Release. 2015 Sep 10;213:69-78.

12.  Huang CY, Sung PJ, Uvarani C, Su JH, Lu MC, Hwang TL, Dai CF, Wu SL, Sheu JH. Glaucumolides A and B, Biscembranoids with New Structural Type from a Cultured Soft Coral Sarcophyton glaucum. Sci Rep. 2015 Nov 4;5:15624.

13.  Tsai YF, Yu HP, Chung PJ, Leu YL, Kuo LM, Chen CY, Hwang TL*. Osthol attenuates neutrophilic oxidative stress and hemorrhagic shock-induced lung injury via inhibition of phosphodiesterase 4. Free Radic Biol Med. 2015 Dec;89:387-400.

14.  Chen CY, Leu YL, Fang Y, Lin CF, Kuo LM, Sung WC, Tsai YF, Chung PJ, Lee MC, Kuo YT, Yang HW, Hwang TL*. Anti-inflammatory effects of Perilla frutescens in activated human neutrophils through two independent pathways: Src family kinases and Calcium. Sci Rep. 2015 Dec:14;5:18204.

15.  Yang SC, Aljuffali IA, Sung CT, Lin CF, Fang JY. Antimicrobial activity of topically-applied soyaethyl morpholinium ethosulfate micelles against Staphylococcus species .Nanomedicine (Lond). 2016 Mar;11(6):657-71.

16.  Chen PJ, Wang YL, Kuo LM, Lin CF, Chen CY, Tsai YF, Shen JJ, Hwang TL*. Honokiol suppresses TNF-α-induced neutrophil adhesion on cerebral endothelial cells by disrupting polyubiquitination and degradation of IκBα. Sci Rep. 2016 May 23;6:26554.

17.  Lee CW, Lin ZC, Hu SC, Chiang YC, Hsu LF, Lin YC, Lee IT, Tsai MH, Fang JY.Urban particulate matter down-regulates filaggrin via COX2 expression/PGE2 production leading to skin barrier dysfunction. Sci Rep. 2016 Jun 17;6:27995.

18.  Liu KS, Chen YW, Aljuffali IA, Chang CW, Wang JJ, Fang JY. Topically applied mesoridazine exhibits the strongest cutaneous analgesia and minimized skin disruption among tricyclic antidepressants: The skin absorption assessment. Eur J Pharm Biopharm. 2016 Aug;105:59-68.

19.  Aljuffali IA, Lin CF, Chen CH, Fang JY.The codrug approach for facilitating drug delivery and bioactivity. Expert Opin Drug Deliv. 2016 Sep;13(9):1311-25.

20.  Wang PW, Hung YC, Li WT, Yeh CT, Pan TL. Systematic revelation of the protective effect and mechanism of Cordycep sinensis on diethylnitrosamine-induced rat hepatocellular carcinoma with proteomics. Oncotarget. 2016 Sep 13;7(37):60270-60289.

21.  Chen YL, Hwang TL, Yu HP, Fang JY, Chong KY, Chang YW, Chen CY, Yang HW, Chang WY, Hsieh PW. Ilex kaushue and Its Bioactive Component 3,5-Dicaffeoylquinic Acid Protected Mice from Lipopolysaccharide-Induced Acute Lung Injury. Sci Rep. 2016 Sep 29;6:34243. doi: 10.1038/srep34243.

22.  Fang JY, Wang PW, Huang CH, Chen MH, Wu YR, Pan TL.Skin aging caused by intrinsic or extrinsic processes characterized with functional proteomics. Proteomics. 2016 Oct;16(20):2718-2731.

23.  Aljuffali IA, Lin YK, Fang JY.Noninvasive approach for enhancing small interfering RNA delivery percutaneously. Expert Opin Drug Deliv. 2016;13(2):265-80.

24.  Chen CY, Yang CH, Tsai YF, Liaw CC, Chang WY, Hwang TL*. Ugonin U stimulates NLRP3 inflammasome activation and enhances inflammasome-mediated pathogen clearance. Redox Biol. 2016 Dec 18;11:263-74.

25.  Hsu CY, Chen CH, Aljuffali IA, Dai YS, Fang JY. Nanovesicle delivery to the liver via retinol binding protein and platelet-derived growth factor receptors: How targeting ligands affect biodistribution. Nanomedicine (Lond). 2017 Feb;12(4):317-331.

26.  Yang SC, Chang SH, Hsieh PW, Huang YT, Ho CM, Tsai YF, Hwang TL*. Dipeptide HCH6-1 inhibits neutrophil activation and protects against acute lung injury by blocking FPR1. Free Radic Biol Med. 2017 Feb 21;106:254-69.

27.  Lin MH, Hung CF, Aljuffali IA, Sung CT, Huang CT, Fang JY.Cationic amphiphile in phospholipid bilayer or oil-water interface of nanocarriers affects planktonic and biofilm bacteria killing. Nanomedicine. 2017 Feb;13(2):353-361.

28.  Tsai YF, Chu TC, Chang WY, Wu YC, Chang FR, Yang SC, Wu TY, Hsu YM, Chen CY, Chang SH, Hwang TL*. 6-Hydroxy-5,7-dimethoxy-flavone suppresses the neutrophil respiratory burst via selective PDE4 inhibition to ameliorate acute lung injury. Free Radic Biol Med. 2017 Mar 3;106:379-92.

【專利】

1.   Pei-Wen Hsieh, Tsong-Long Hwang, Wen-Hui Wang, Ting-Yi Wang.

Oxime-based compound, pharmaceutical composition containing the same and method for preparing the same cross-reference to related application.

United States Patent Number:US9,073,833 B1. (Issued:2015/07/07)

2.  謝珮文、黃聰龍、王雯慧、王婷儀

2-胺基苯甲醛肟衍生物及其製備方法與用途。

中華民國發明專利第 I 508938號(2015/11/21)

3.  謝珮文、黃聰龍、王雯慧、王婷儀

2-胺基苯甲醛肟衍生物及其製備方法與用途。

日本特許證 特許第5890512號(2016/02/26) 

4.  黃聰龍、謝珮文、黃吟婷、洪志豪。

FPR1拮抗劑的衍生物及其用途。

中華民國發明專利第 I 537251號(2016/06/11) 

5.  陳金銓、呂彥禮、黃聰龍、方嘉佑、潘台龍。

哺乳類SIRT1的活化劑。

中華民國發明專利第 I 556818號(2016/11/11) 

6.  Tsong-Long Hwang, Pei-Wen Hsieh, Yin-Ting Huang,Chih-Hao Hung.

FPR1 ANTAGONIST DERIVATIVES AND USE THEREOF

United States Patent Number:US 9,593,144 B2. (Issued:2017/03/14)

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