Fol. Biol. 2021, 67, 126-133

https://doi.org/10.14712/fb2021067030126

Luteoloside Ameliorates Palmitic Acid-Induced in Vitro Model of Non-alcoholic Fatty Liver Disease via Activating STAT3-Triggered Hepatocyte Regeneration

Y. X. Zhu1, L. Zhu1, Y. F. Chen1, J. M. Xu1, Z. L. Shen1, R. J. Liu1, J. Zou1, Mingqing Yuan1, Fan Ye1, Qingqi Zeng2

1Department of Pharmacy, Affiliated Kunshan Hospital of Jiangsu University, Kunshan 215300, Jiangshu, China
2Jiangsu Health Vocational College; Nanjing 210023, China

Received May 2021
Accepted September 2021

Luteoloside (Lute), a bioactive natural ingredient, widely exists in nature and possesses hepatoprotective and hepatocyte proliferation-promoting properties. This study aimed to investigate whether Lute could counteract non-alcoholic fatty liver disease (NAFLD)-caused hepatocyte damage via its stimulation of hepatocyte regeneration efficacy and to explore the involved mechanism. LO2 cells and primary hepatocytes were used to examine the hepatocyte proliferation effects of Lute under physiological conditions and in the palmitic acid (PA)- induced in vitro model of NAFLD. STAT3 and cell cycle-related proteins (cyclin D1, c-myc and p21) were evaluated by Western blot. Under physiological conditions, LO2 cells and primary hepatocytes treated with various concentration of Lute for 12 and 24 h showed increased hepatocyte proliferation, especially with 20 μM treatment for 24 h. More notably, under the model conditions, co-incubation with 20 μM of Lute also markedly reversed PA-induced inhibition of cell proliferation and viability in primary hepatocytes. Mechanistically, Lute could activate STAT3 and subsequently increase cyclin D1 and cmyc expression, which positively regulates cell cycle progression, and decrease expression of p21, an inhibitor of cell cycle progression. Furthermore, Luteinduced hepatocyte proliferation-promoting efficacy was abolished by STAT3 inhibitor stattic. Collectively, Lute can alleviate PA-induced hepatocyte damage via activating STAT3-mediated hepatocyte regeneration.

Funding

This work was supported by the Project of State Administration of Chinese Medicine (NZYJDMF-2020001), Medical Scientific Research Project of Jiangsu Provincial Health Commission (ZDB2020020) and University-Level Project of Jiangsu Health Vocational College (JKA201916).

References

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