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Dihydronortanshinone, a natural product, alleviates LPS-induced inflammatory response through NF-κB, mitochondrial ROS, and MAPK pathways
Wu X.4; Gao H.4; Hou Y.4; Yu J.4; Sun W.4; Wang Y.4; Chen X.1; Feng Y.2; Xu Q.-M.3; Chen X.4
2018-09-15
Source PublicationToxicology and Applied Pharmacology
ISSN10960333 0041008X
Volume355Pages:1-8
Abstract

Inflammation is considered to be the common pathophysiological basis for a series of diseases. Documented data showed the anti-inflammatory effects of Salvia miltiorrhiza Bunge (Danshen), a traditional herb. The pharmacological activities of dihydronortanshinone (DNT), a tanshinone isolated from Danshen, remain unknown. In this study, the anti-inflammatory effects and underlying mechanisms of DNT were investigated with a lipopolysaccharide (LPS)-induced RAW264.7 macrophage model. DNT significantly suppressed LPS-induced inflammatory mediators such as nitrite oxide (NO), tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), inducible nitric oxide synthase (iNOS). LPS-induced reactive oxygen species (ROS) generation was inhibited by DNT, rotenone (Rot), thenoyltrifluoroacetone (TTFA), and antimycin A (AA). Furthermore, DNT inhibited LPS-induced NF-κBp65 phosphorylation, nuclear translocation, as well as JNK1/2 and p38MAPK phosphorylation. In addition, DNT interrupted Toll-like receptor 4 (TLR4) dimerization and molecular docking results suggested that it was buried in the pocket of TLR4-MD2 complex. In conclusion, DNT inhibited LPS-induced inflammation mainly through NF-κB, mitochondrial ROS, and MAPK pathways possibly mediated by interfering LPS-TLR4-MD2 complex.

KeywordDihydronortanshinone Inflammation Lps Macrophage
DOIhttp://doi.org/10.1016/j.taap.2018.06.007
URLView the original
Indexed BySCI
Language英语
WOS Research AreaPharmacology & Pharmacy ; Toxicology
WOS SubjectPharmacology & Pharmacy ; Toxicology
WOS IDWOS:000442193300001
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Cited Times [WOS]:5   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Affiliation1.Zunyi Medical College
2.Jiangxi University of Traditional Chinese Medicine
3.Soochow University
4.Universidade de Macau
Recommended Citation
GB/T 7714
Wu X.,Gao H.,Hou Y.,et al. Dihydronortanshinone, a natural product, alleviates LPS-induced inflammatory response through NF-κB, mitochondrial ROS, and MAPK pathways[J]. Toxicology and Applied Pharmacology,2018,355:1-8.
APA Wu X..,Gao H..,Hou Y..,Yu J..,Sun W..,...&Chen X..(2018).Dihydronortanshinone, a natural product, alleviates LPS-induced inflammatory response through NF-κB, mitochondrial ROS, and MAPK pathways.Toxicology and Applied Pharmacology,355,1-8.
MLA Wu X.,et al."Dihydronortanshinone, a natural product, alleviates LPS-induced inflammatory response through NF-κB, mitochondrial ROS, and MAPK pathways".Toxicology and Applied Pharmacology 355(2018):1-8.
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