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Anti-inflammatory effects of guggulsterone on murine macrophage by inhibiting LPS-induced inflammatory cytokines in NF-κB signaling pathway

Authors Zhang J, Shangguan Z, Chen C, Zhang H, Lin Y

Received 19 January 2016

Accepted for publication 14 March 2016

Published 1 June 2016 Volume 2016:10 Pages 1829—1835

DOI https://doi.org/10.2147/DDDT.S104602

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Prof. Dr. Wei Duan


Jin-Hua Zhang,1,2,* Zhao-Shui Shangguan,3,* Chao Chen,4 Hui-Jie Zhang,4 Yi Lin1

1College of Chemical Engineering, Huaqiao University, 2Department of Pharmacy, Xiamen Medical College, 3Central Laboratory, The First Affiliated Hospital of Xiamen University, 4Xiamen Diabetes Institute, The First Affiliated Hospital of Xiamen University, Xiamen, People’s Republic of China

*These authors contributed equally to this work

Abstract:
The present study was aimed to investigate the effects of guggulsterone (GS) on proinflammatory responses as well as the underlying molecular mechanisms in macrophage upon lipopolysaccharide (LPS) stimulation. Effects of GS on viability of Raw264.7 cells were examined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Real-time polymerase chain reaction (PCR) was employed to examine the mRNA expression of cytokines, including interleukin 1β (IL-1β), tumor necrosis factor-alpha (TNF-α), and inducible nitric oxide synthase (iNOS). Phosphorylations of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinases (p38), and inhibitor of nuclear factor kappaB (IκB) were determined using immunoblotting. The results revealed that GS was not toxic to Raw264.7 cells at designated concentrations. We demonstrated that GS significantly suppressed the elevated mRNA expression of proinflammatory cytokines, including IL-1β, TNF-α, and iNOS in a dose-dependent manner. GS treatment reduced the level of IκB phosphorylation in LPS-stimulated macrophages in a dose-dependent manner. Use of BAY 11-7082, an inhibitor of nuclear factor-kappaB (NF-κB), led to significantly suppressing effects on IL-1β and TNF-α expression similar as that of GS-treated cells. Our findings suggest that GS possesses anti-inflammatory activity, which may be attributed to downregulation of iNOS and inhibition of NF-κB activity in LPS-stimulated Raw264.7 cells.

Keywords: Anti-inflammatory effects, guggulsterone, lipopolysaccharides, NF-κB, IL-1β, TNF-α

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