School of Traditional Chinese Medicine

Research Topics

This laboratory focuses on the physiological and pathological mechanisms underlying metabolic diseases and chronic inflammation, with particular emphasis on the integrated regulation of the gut–liver–kidney axis and its interactions with renal function deterioration, metabolic reprogramming, and inflammatory–immune imbalance. By integrating interdisciplinary approaches such as molecular pharmacology, immunometabolism, and microbiomics, the laboratory has established multiple disease models, including high-fat/high-sugar diet, bile duct ligation, and DSS- and LPS-induced models, for systematic investigation. The goal is to identify key signaling nodes and therapeutic strategies with translational potential.

1. Renal Physiology and Pathological Mechanisms
This laboratory investigates the roles of mitochondrial dysfunction and impaired autophagy in the progression of kidney injury. Special attention is given to regulatory molecules such as FXR and SIRT1 in order to elucidate their potential in maintaining renal function and reversing pathological changes, thereby laying the foundation for future precision intervention strategies.

2. Signal Regulation of the Gut–Liver–Kidney Axis
This research examines the bridging roles of the gut microbiota and metabolites such as bile acids in the regulation of liver and kidney function. It also evaluates the role of the FXR–Klotho–FGF pathway in intestinal barrier protection and tumor microenvironment regulation, while exploring functional intervention strategies with the potential to modulate communication along the gut–liver–kidney axis.

3. Metabolic Regulation in Obesity and MAFLD
This laboratory focuses on elucidating the key mechanisms by which a high-fat/high-sugar diet induces hepatic lipotoxicity, mitochondrial dysfunction, and immunometabolic imbalance, and further investigates the systemic regulatory network involved in the progression of metabolic dysfunction–associated fatty liver disease (MAFLD). Recent studies suggest that Losartan, through its regulatory effects on HIF-1α, macrophage polarization, and mitochondrial function, may provide mechanistic support for therapeutic strategies against MAFLD. An integrated evaluation platform is also being established to identify therapeutic targets with translational potential.

4. Regulation of Intestinal Barrier Function and Colitis
Using experimental colitis models, such as DSS- and LPS-induced models, this laboratory investigates the mechanisms governing intestinal barrier stability, mucosal immunity, and microbiota regulation. By combining natural compound interventions with multi-omics analyses, future studies aim to construct a molecular map of intestinal barrier injury and repair, thereby facilitating the development of potential therapeutic strategies with preventive and translational value.

Laboratory Members

Areas of Expertise

1. Renal Physiology and Pathology
2. Integrated Physiological Regulation of the Gut–Liver–Kidney Axis
3. Obesity and Metabolic Dysfunction–Associated Fatty Liver Disease (MAFLD)
4. Experimental Colitis and Intestinal Barrier Function

Publications

1. Yang CW, Liu HM, Chang ZY, Liu GH, Chang HH, Huang PY, Lee TY. Puerarin Modulates Hepatic Farnesoid X Receptor and Gut Microbiota in High-Fat Diet-Induced Obese Mice. Int J Mol Sci. 2024 May 12;25(10):5274. doi: 10.3390/ijms25105274.

2. Liu HM, Chang ZY, Yang CW, Chang HH, Lee TY. Farnesoid X Receptor Agonist GW4064 Protects Lipopolysaccharide-Induced Intestinal Epithelial Barrier Function and Colorectal Tumorigenesis Signaling through the αKlotho/βKlotho/FGFs Pathways in Mice. Int J Mol Sci. 2023 Nov 29;24(23):16932. doi: 10.3390/ijms242316932.

3. Huang PY, Liu HM, Ko YR, Chang ZY, Lee TY. Electroacupuncture relieves portal hypertension by improving vascular angiogenesis and linking gut microbiota in bile duct ligation rats. Front Microbiol. 2023 Jul 11;14:1207137. doi: 10.3389/fmicb.2023.1207137.

4. Wang CH, Liu HM, Chang ZY, Lee MC, Hsu CH, Lee TY. 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. Front Biosci (Landmark Ed). 2022 Aug 15;27(8):242. doi: 10.31083/j.fbl2708242.

5. Chou YT, Liu TT, Yang UC, Huang CC, Liu CW, Huang SF, Li TH, Liu HM, Lin MW, Yang YY, Lee TY, Huang YH, Hou MC, Lin HC. Intestinal SIRT1 Deficiency-Related Intestinal Inflammation and Dysbiosis Aggravate TNFα-Mediated Renal Dysfunction in Cirrhotic Ascitic Mice. Int J Mol Sci. 2021 Jan 27;22(3):1233. doi: 10.3390/ijms22031233.

6. Wang CH, Liu HM, Chang ZY, Huang TH, Lee TY. Losartan Prevents Hepatic Steatosis and Macrophage Polarization by Inhibiting HIF-1α in a Murine Model of NAFLD. Int J Mol Sci. 2021 Jul 22;22(15):7841. doi: 10.3390/ijms22157841.

7. Liu GH, Zhuo XC, Huang YH, Liu HM, Wu RC, Kuo CJ, Chen NH, Chuang LP, Lin SW, Chen YL, Yang HY, Lee TY. 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 Jun 25;11(7):962. doi: 10.3390/biology11070962.

8. Chang ZY, Liu HM, Leu YL, Hsu CH, Lee TY. Modulation of Gut Microbiota Combined with Upregulation of Intestinal Tight Junction Explains Anti-Inflammatory Effect of Corylin on Colitis-Associated Cancer in Mice. Int J Mol Sci. 2022 Feb 28;23(5):2667. doi: 10.3390/ijms23052667.

9. Liu HM, Wang CH, Chang ZY, Huang TH, Lee TY. Losartan Attenuates Insulin Resistance and Regulates Browning Phenomenon of White Adipose Tissue in ob/ob Mice. Curr Issues Mol Biol. 2021 Oct 28;43(3):1828-1843. doi: 10.3390/cimb43030128.

10. Yeh CC, Liu HM, Lee MC, Leu YL, Chiang WH, Chang HH, Lee TY. 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. Mol Med Rep. 2022 Feb;25(2):57. doi: 10.3892/mmr.2021.12572.

11. Chen YS, Liu HM, Lee TY. Ursodeoxycholic Acid Regulates Hepatic Energy Homeostasis and White Adipose Tissue Macrophages Polarization in Leptin-Deficiency Obese Mice. Cells. 2019 Mar 16;8(3):253. doi: 10.3390/cells8030253.

12. Chang ZY, Chen CC, Liu HM, Yeh YC, Lin TY, Lee TY, Huang TH. Positive Effects of Ger-Gen-Chyn-Lian-Tang on Cholestatic Liver Fibrosis in Bile Duct Ligation-Challenged Mice. Int J Mol Sci. 2019 Aug 26;20(17):4181. doi: 10.3390/ijms20174181.

13. Huang TH, Chen CC, Liu HM, Lee TY, Shieh SH. Resveratrol Pretreatment Attenuates Concanavalin A-induced Hepatitis through Reverse of Aberration in the Immune Response and Regenerative Capacity in Aged Mice. Sci Rep. 2017 Jun 2;7(1):2705. doi: 10.1038/s41598-017-02881-z.

14. Liu HM, Liao JF, Lee TY. Farnesoid X receptor agonist GW4064 ameliorates lipopolysaccharide-induced ileocolitis through TLR4/MyD88 pathway related mitochondrial dysfunction in mice. Biochem Biophys Res Commun. 2017 Aug 26;490(3):841-848. doi: 10.1016/j.bbrc.2017.06.129.

15. Liu GH, Liu HM, Chen YS, Lee TY. Effect of Electroacupuncture in Mice with Dextran Sulfate Sodium-Induced Colitis and the Influence of Gut Microbiota. Evid Based Complement Alternat Med. 2020 Apr 27;2020:2087903. doi: 10.1155/2020/2087903.

16. Tsai YL, Liu CW, Hsu CF, Huang CC, Lin MW, Huang SF, Li TH, Lee KC, Hsieh YC, Yang YY, Lee TY, Liu HM, Huang YH, Hou MC, Lin HC. Obeticholic acid ameliorates hepatorenal syndrome in ascitic cirrhotic rats by down-regulating the renal 8-iso-PGF2α-activated COX-TXA2 pathway. Clin Sci (Lond). 2020 Aug 14;134(15):2055-2073. doi: 10.1042/CS20200452.

17. Li TH, Tsai YL, Hsu CF, Liu CW, Huang CC, Yang YY, Tsai HC, Huang SF, Hsieh YC, Liu HM, Lee TY, Hou MC, Tsai CY, Lin HC. Propranolol Is Associated with Lower Risk of Incidence of Hepatocellular Carcinoma in Patients with Alcoholic Cirrhosis: A Tertiary-Center Study and Indirect Comparison with Meta-Analysis. Gastroenterol Res Pract. 2020 Apr 9;2020:1892584. doi: 10.1155/2020/1892584.

18. Liu HM, Lee TY, Liao JF. GW4064 attenuates lipopolysaccharide‑induced hepatic inflammation and apoptosis through inhibition of the Toll‑like receptor 4‑mediated p38 mitogen‑activated protein kinase signaling pathway in mice. Int J Mol Med. 2018 Mar;41(3):1455-1462. doi: 10.3892/ijmm.2018.3366.