The Exploration of Anti-aging Nutraceuticals

PI : Tsong-Long Hwang

Research Expertise: Signal Transduction, Natural Pharmaceutics, New Drug Development

Researchers

Tsong-Long Hwang, Jia-You Fang, Sien-Hung Yang, Tai-Long Pan, Chin-Chuan Chen, Yann-Lii Leu

Yung-Fong Tsai, Huang-Ping Yu, Chun-Yu Chen, Ting-I Kao

Conceptual Framework

Study Purpose

Chinese herbal medicine provides valuable information in the development of modern medicine. The Chinese Herbal Medicine Research Team aims to develop translational research in Chinese herbal medicine and the development of new drugs based on Chinese herbal medicine. We have started and will continue to research and develop the extracts and pure compounds from Chinese herbal medicine for health promotion or diseases prevention purposes in the elders. The enzyme, cellular, and animals studies and clinical trials with the pure compounds and extracts are performed to establish the pharmacological and toxicological profiles. The biomarkers and risk factors developed from MMRC and HARC will be examined and studied to evaluate the efficacy and specificity of Chinese herbal medicine.

Development Strategy

1.  Establish high-throughput cell-based screening platforms and animal disease models to study the pharmacodynamics, pharmacology, and pharmacokinetics of potential herbal medicines.

2.  Study the potential herbal medicines for developing better therapeutic strategies for aging and/or aging related diseases.

3.  Development of potential herbal medicines for therapeutic approach and translational research.

4.  The structures of potential compounds from herbal medicines are used as leads in the development of new drugs.

Accomplishments

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.

【Patent】

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

2-AMINOBENZALDEHYDE OXIME DERIVATIVES, AND THE PREPARATION PROCESSES AND USES THEREOF.

Taiwan Patent Number: I 508938(Issued:2015/11/21)

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

2-AMINOBENZALDEHYDE OXIME DERIVATIVES, AND THE PREPARATION PROCESSES AND USES THEREOF.

Japan Patent Number: 5890512(Issued:2016/02/26)

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

FPR1 ANTAGONIST DERIVATIVES AND USE THEREOF

Taiwan Patent Number: I 537251(Issued:2016/06/11) 

5.  Chin-Chuan, Chen,Yann-Lii Leu, Tsong-Long Hwang, Jia-You Fang, Tai-Long Pan.

ACTIVATOR OF MAMMALIAN SIRT1

Taiwan Patent Number: I 556818(Issued: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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