Sodium Tanshinone IIA Sulfonate Decreases Cigarette Smoke-Induced Inflammation and Oxidative Stress via Blocking the Activation of MAPK/HIF-1α Signaling Pathway

Frontiers in Pharmacology
Ruijuan GuanWenju Lu

Abstract

Aberrant activation of hypoxia-inducible factor (HIF)-1α is frequently encountered and promotes oxidative stress and inflammation in chronic obstructive pulmonary disease (COPD). The present study investigated whether sodium tanshinone IIA sulfonate (STS), a water-soluble derivative of tanshinone IIA, can mediate its effect through inhibiting HIF-1α-induced oxidative stress and inflammation in cigarette smoke (CS)-induced COPD in mice. Here, we found that STS improved pulmonary function, ameliorated emphysema and decreased the infiltration of inflammatory cells in the lungs of CS-exposed mice. STS reduced CS- and cigarette smoke extract (CSE)-induced upregulation of tumor necrosis factor (TNF)-α and interleukin (IL)-1β in the lungs and macrophages. STS also inhibited CSE-induced reactive oxygen species (ROS) production, as well as the upregulation of heme oxygenase (HO)-1, NOX1 and matrix metalloproteinase (MMP)-9 in macrophages. In addition, STS suppressed HIF-1α expression in vivo and in vitro, and pretreatment with HIF-1α siRNA reduced CSE-induced elevation of TNF-α, IL-1β, and HO-1 content in the macrophages. Moreover, we found that STS inhibited CSE-induced the phosphorylation of ERK, p38 MAPK and JNK in macrophages, and i...Continue Reading

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Citations

Nov 28, 2019·Naunyn-Schmiedeberg's Archives of Pharmacology·Walaa Yehia AbdelzaherMina Ezzat Attya
Jan 20, 2021·Expert Review of Clinical Pharmacology·Jun FengJunshuai Wang
Feb 9, 2021·Frontiers in Immunology·Nathan P CrillyPetros C Karakousis

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Methods Mentioned

BETA
lavage
ELISA
Transfection
PCR
FCS
Scanning densitometry

Software Mentioned

SigmaPlot
Image Pro Plus
Image J

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