Sclareol attenuates liver fibrosis through SENP1-mediated VEGFR2 SUMOylation and inhibition of downstream STAT3 signaling.

Autor: Ge MX; Department of Pharmacy, Qilu Hospital of Shandong University, Jinan, China., Niu WX; Medical Department, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China., Bao YY; Key Laboratory of Biotechnology of Antibiotics, the National Health and Family Planning Commission (NHFPC), Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China., Lu ZN; Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing, China., He HW; Key Laboratory of Biotechnology of Antibiotics, the National Health and Family Planning Commission (NHFPC), Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Jazyk: angličtina
Zdroj: Phytotherapy research : PTR [Phytother Res] 2023 Sep; Vol. 37 (9), pp. 3898-3912. Date of Electronic Publication: 2023 May 02.
DOI: 10.1002/ptr.7845
Abstrakt: Liver fibrosis is a key global health care burden. Sclareol, isolated from Salvia sclarea, possesses various biological activities. Its effect on liver fibrosis remains unknown. This study was proposed to evaluate the antifibrotic activity of sclareol (SCL) and explore its underlying mechanisms. Stimulated hepatic stellate cells served as an in vitro liver fibrosis model. The expression of fibrotic markers was assessed by western blot and real-time PCR. Two classical animal models, bile duct-ligated rats and carbon tetrachloride-treated mice, were utilized for the in vivo experiments. The liver function and fibrosis degree were determined by serum biochemical and histopathological analyses. VEGFR2 SUMOylation was analyzed using coimmunoprecipitation assay. Our results indicated that SCL treatment restricted the profibrotic propensity of activated HSCs. In fibrotic rodents, SCL administration alleviated hepatic injury and reduced collagen accumulation. Mechanistic studies indicated that SCL downregulated the protein level of SENP1 and enhanced VEGFR2 SUMOylation in LX-2 cells, which affected its intracellular trafficking. Blockade of the interaction between VEGFR2 and STAT3 was observed, resulting in the suppression of downstream STAT3 phosphorylation. Our findings demonstrated that SCL has therapeutic efficacy against liver fibrosis through mediating VEGFR2 SUMOylation, suggesting that SCL may be a potential candidate compound for its treatment.
(© 2023 John Wiley & Sons Ltd.)
Databáze: MEDLINE
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