Methyl ferulic acid ameliorates alcohol-induced hepatic insulin resistance via miR-378b-mediated activation of PI3K-AKT pathway.

Abstract

A previous study indicated that microRNA-378b (miR-378b) plays a critical role in controlling hepatic insulin resistance by targeting insulin receptor (IR) and p110α in alcoholic liver disease (ALD). Methyl ferulic acid (MFA), a bioactive ingredient in Securidaca inappendiculata Hassk rhizomes, exhibits multiple pharmacological activities. It has been reported that MFA ameliorates insulin resistance in ALD, whereas the underlying molecular mechanism remains unclear. The objective of study was to evaluate the influence of MFA on insulin sensitivity in ethanol-induced L-02 cells as well as alcohol-fed mice and illuminate the function of miR-378b-mediated phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway in system. MFA was found to remarkably down-regulate miR-378b level and increase IR and p110α expressions. Furthermore, the effect of MFA on modulating miR-378b/PI3K-AKT pathway to enhance insulin sensitivity was corroborated by overexpressing and inhibiting miR-378b. Taken together, MFA exhibited a positive effect against ALD by attenuating the inhibition of miR-378b on IR/p110α and partly activating the insulin signaling to alleviate alcohol-induced hepatic insulin resistance.

• Authors: Yan Zhang, Jun Lu, Yu-Juan Zhong, Cheng-Fang Yang, Li Chen, Dan Wu, Meng-Wei Song, Lin Shi, Zu-Heng Ma, Li Li, Yong-Wen Li
• Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Biomed Pharmacother) Vol. 145 Pg. 112462 (Jan 2022) ISSN: 1950-6007 [Electronic] France
• PMID: 34844105 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

Chemical References

• Caffeic Acids
• MIRN378 microRNA, mouse
• MicroRNAs
• Phytochemicals
• 1-phosphatidylinositol 3-kinase p110 subunit, mouse
• Class I Phosphatidylinositol 3-Kinases
• Phosphatidylinositol 3-Kinase
• Receptor, Insulin
• Proto-Oncogene Proteins c-akt
• methyl ferulate

Topics

• Animals
• Caffeic Acids (pharmacology)
• Class I Phosphatidylinositol 3-Kinases (metabolism)
• Gene Expression Regulation (drug effects)
• Insulin Resistance (physiology)
• Liver Diseases, Alcoholic (drug therapy, metabolism)
• Mice
• MicroRNAs (metabolism)
• Phosphatidylinositol 3-Kinase (metabolism)
• Phytochemicals
• Proto-Oncogene Proteins c-akt (metabolism)
• Receptor, Insulin (metabolism)
• Securidaca
• Signal Transduction (drug effects)
• Up-Regulation