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Beneficial Effects of a Curcumin Derivative and Transforming Growth Factor-β Receptor I Inhibitor Combination on Nonalcoholic Steatohepatitis
- Title
- Beneficial Effects of a Curcumin Derivative and Transforming Growth Factor-β Receptor I Inhibitor Combination on Nonalcoholic Steatohepatitis
- Authors
- Ha, Kyung Bong; Lee, Eun Soo; Park, Na Won; Jo, Su Ho; Shim, Soyeon; Kim, Dae-Kee; Ahn, Chan Mug; Chung, Choon Hee
- Ewha Authors
- 김대기
- SCOPUS Author ID
- 김대기
- Issue Date
- 2023
- Journal Title
- DIABETES & METABOLISM JOURNAL
- ISSN
- 2233-6079
2233-6087
- Citation
- DIABETES & METABOLISM JOURNAL vol. 47, no. 4, pp. 500 - 513
- Keywords
- ALK5 inhibitor; Curcumin; Fibrosis; Non-alcoholic fatty liver disease; Transforming growth factor beta
- Publisher
- KOREAN DIABETES ASSOC
- Indexed
- SCIE; SCOPUS; KCI
- Document Type
- Article
- Abstract
- Background: Curcumin 2005-8 (Cur5-8), a derivative of curcumin, improves fatty liver disease via AMP-activated protein kinase activation and autophagy regulation. EW-7197 (vactosertib) is a small molecule inhibitor of transforming growth factor & beta; (TGF-& beta;) receptor I and may scavenge reactive oxygen species and ameliorate fibrosis through the SMAD2/3 canonical pathway. This study aimed to determine whether co-administering these two drugs having different mechanisms is beneficial.Methods: Hepatocellular fibrosis was induced in mouse hepatocytes (alpha mouse liver 12 [AML12]) and human hepatic stellate cells (LX-2) using TGF-& beta; (2 ng/mL). The cells were then treated with Cur5-8 (1 & mu;M), EW-7197 (0.5 & mu;M), or both. In animal ex-periments were also conducted during which, methionine-choline deficient diet, Cur5-8 (100 mg/kg), and EW-7197 (20 mg/kg) were administered orally to 8-week-old C57BL/6J mice for 6 weeks.Results: TGF-& beta;-induced cell morphological changes were improved by EW-7197, and lipid accumulation was restored on the ad-ministration of EW-7197 in combination with Cur5-8. In a nonalcoholic steatohepatitis (NASH)-induced mouse model, 6 weeks of EW-7197 and Cur5-8 co-administration alleviated liver fibrosis and improved the nonalcoholic fatty liver disease (NAFLD) ac-tivity score. Conclusion: Co-administering Cur5-8 and EW-7197 to NASH-induced mice and fibrotic hepatocytes reduced liver fibrosis and steatohepatitis while maintaining the advantages of both drugs. This is the first study to show the effect of the drug combination against NASH and NAFLD. Similar effects in other animal models will confirm its potential as a new therapeutic agent.
- DOI
- 10.4093/dmj.2022.0110
- Appears in Collections:
- 약학대학 > 약학과 > Journal papers
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