Silibinin protects GLUTag cells from PA-induced injury via suppressing endoplasmic reticulum stress

ABSTRACT

Silibinin is a natural flavonoid with anti-diabetic activity. Glucagon-like peptide−1 (GLP−1), an intestinal hormone mainly secreted from L cells, which regulates insulin production and sensitivity, appears to be a potential therapeutic strategy for T2DM. The current study aims to determine the protective effect of silibinin against palmitic acid (PA)-induced damage in GLUTag cells. The results revealed that PA triggered endoplasmic reticulum (ER) stress and apoptosis in GLUTag cells, while silibinin attenuated PA-induced lipotoxicity. Based on the estrogen-like effects of silibinin and the role of estrogen receptors in regulating glycolipid metabolism, the involvement of estrogen receptors in the protective effects of silibinin in GLUTag cells was further investigated. The results showed that estrogen receptor α- and β-specific inhibitors reversed the inhibitory impact of silibinin on ER stress. Our study demonstrated that silibinin protects GLUTag cells from PA-induced injury by decreasing ER stress under the regulation of estrogen receptors α and β.

KEYWORDS:

• Silibinin
• palmitic acid
• estrogen receptors α and β
• ER stress

Acknowledgements

We thank Dr. Daniel J. Drucker of The University of Toronto for kindly providing GLUTag cell line.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Author contribution

Conceptualization, X.S., C.C. and F.X.; methodology, X.L., L.Z. and F.X.; data collection, X.S., C.C., X.L. and L.Z.; validation, X.Z. and N.C.; formal analysis, W.L., Z.J. and C.C.; writing-original draft preparation, X.S., C.C. and L.Z.; writing-review and editing, F.X. and T.I.; funding acquisition, F.X.; supervision, F.X. and T.I. All authors have read and agreed to the published version of the manuscript. All data were generated in-house. All authors agree to be accountable for all aspects of work ensuring integrity and accuracy.

Additional information

Funding

This work was funded by National Natural Science Foundation of China [grant number 81803603], Natural Science Foundation of Liaoning Province [grant number 2020-MS-195], Foundation of Liaoning Educational Committee [grant number LJKZ0932], Project funded by China Postdoctoral Science Foundation [grant number 2021M691324, 2017M621161, 2018T110462], Shenyang Young and Middle-aged Scientific and Technological Innovation Talents Support Project [grant number RC220420], and Excellent Young Scholars Program of Shenyang Pharmaceutical University [grant number YQ202114].