AUTHOR=Ma Yunfei , Liu Ying , Ma Yunyan , Jiang Nan , Wang Lei , Wang Bowei , Niu Wanting , Hu Yanjun , Lin Qingrong , Yu Bin TITLE=Mangiferin Relieves Lipopolysaccharide-Induced Injury by Up-Regulating miR-181a via Targeting PTEN in ATDC5 Cells JOURNAL=Frontiers in Pharmacology VOLUME=11 YEAR=2020 URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2020.00137 DOI=10.3389/fphar.2020.00137 ISSN=1663-9812 ABSTRACT=Background

Mangiferin (MF) was reported to possess anti-inflammatory activity. This investigation tried to probe into the underlying mechanism of MF in osteoarthritis.

Methods

ATDC5 cells were pretreated with series concentrations of MF (0.1, 1, 5, 10, 15, 20 μM) for 2 h and then were exposed to lipopolysaccharide (LPS) (5 μg/ml) for 12 h to construct the inflammatory injury model. The cell viability, productions of pro-inflammatory cytokines and enzymes were respectively measured by employing CCK-8 assay, western blot, ELISA, and quantitative reverse-transcription (qRT)-PCR. miR-181a expression was altered by employing cell transfection. Dichloro-dihydro-fluorescein diacetate (DCFH-DA) method was employed for detection of reactive oxygen species (ROS) generation. Dual luciferase activity assay was conducted for analyzing the relationship between miR-181a and PTEN. The underlying mechanism was determined by employing western blot.

Results

High doses of MF treatment (15 and 20 μM) noticeably induced inflammatory injury exhibiting as increased the productions of pro-inflammatory cytokines, enzymes and ROS, activated NF-κB pathway and deactivated PTEN/PI3K/AKT pathway in ATDC5 cells. Besides, MF treatment notably remitted LPS-induced inflammatory injury through deactivation of NF-κB pathway and activation of PTEN/PI3K/AKT pathway. PTEN was a target of miR-181a. Inhibition of miR-181a remarkably reversed MF-triggered impacts on ATDC5 cells.

Conclusion

MF attenuated LPS-induced inflammatory damage through miR-181a/PTEN axis and thereby inhibiting NF-κB pathway and activating PI3K/AKT pathway.