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Andrographolide attenuates oxidative stress injury in cigarette smoke extract exposed macrophages through inhibiting SIRT1/ERK signaling.

Abstract：

:Andrographolide (AG), an ingredient extracted from traditional Chinese herbal medicine Andrographis paniculata, has been demonstrated to have potent anti-inflammatory and anti-oxidative stress properties. The purpose of this study was to investigate whether and how AG attenuated CSE-induced mitochondrial dysfunction, inflammation and oxidative stress in RAW 264.7 cells (a mouse macrophages line). The results showed that AG significantly reduced CSE-induced upregulation of pro-inflammatory cytokines (i.e., TNF-α and IL-1β) in the RAW 264.7 cells. AG inhibited CSE-induced production of reactive oxygen species (ROS) and prevented the reduction of superoxide dismutase (SOD) and glutathione/oxidized glutathione (GSH/GSSG) ratio, indicating the anti-oxidative stress effects of AG in macrophages. AG also improved mitochondrial function and mitochondrial membrane potential. In addition, AG inhibited CSE-induced increase of heme oxygenase (HO)-1, matrix metalloproteinase (MMP)-9 and MMP-12. Moreover, AG increased SIRT1 transcription and expression, suggesting AG inhibits mitochondrial dysfunction, inflammation and oxidative stress via a SIRT1 dependent signaling. We also demonstrated that AG inhibited CSE-induced ERK phosphorylation, and treatment with PD980589, a ERK inhibitor, reversed CSE-induced inflammation and oxidative stress. These results indicated that AG may prevent COPD via the inhibition of SIRT1/ERK signaling pathway, and subsequently inhibition of mitochondrial dysfunction, inflammation, and oxidative stress in macrophages.

journal_name

Int Immunopharmacol

journal_title

International immunopharmacology

authors

Zhang XF,Ding MJ,Cheng C,Zhang Y,Xiang SY,Lu J,Liu ZB

doi

10.1016/j.intimp.2020.106230

subject

Has Abstract

pub_date

2020-04-01 00:00:00

pages

106230

eissn

1567-5769

issn

1878-1705

pii

S1567-5769(19)31533-4

journal_volume

81

pub_type

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