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Cryptotanshinone from Salvia miltiorrhiza Bunge (Danshen) inhibited inflammatory responses via TLR4/MyD88 signaling pathway
Li, Xin Xing1,2; Zheng, Xiaoting3; Liu, Zhenjie1,2; Xu, Qiongming1,4; Tang, Hongzhen1,2; Feng, Jianfang1,2; Yang, Shilin1,2; Vong, Chi Teng3; Gao, Hongwei1,2; Wang, Yitao3
Source PublicationChinese Medicine

Background: Cryptotanshinone (CPT), as a major component of Salvia miltiorrhiza Bunge (Danshen), displays many pharmacological activities including anti-inflammatory effects. However, the exact cellular and molecular mechanisms of the anti-inflammatory activities of CPT remain to be elucidated. The present study was aimed to clarify its mechanisms on lipopolysaccharide (LPS)-induced inflammatory responses in mouse macrophages, RAW264.7 cells. Methods: In the current study, the anti-inflammatory properties of CPT were evaluated using LPS-stimulated RAW264.7 cell model. MTT assay was used to determine the viability of RAW264.7 cells. The anti-inflammatory effects of CPT were measured based on the detection of nitric oxide (NO) production (Griess and flow cytometry assay), and tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) release (ELISA). Cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) enzyme expressions were also determined by western blotting. Besides, by using flow cytometry, we also evaluated the effect of CPT on LPS-induced calcium influx. Finally, the underlying anti-inflammatory mechanisms of CPT were investigated using western blotting to assess the protein levels of toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), phosphatidylinositol 3-kinase (PI3K)/AKT, nuclear factor erythroid 2 related factor 2 (Nrf2), mitogen-activated protein kinase (MAPK), and nuclear factor-kappa B (NF-κB) pathways. Results: Our data showed that CPT inhibited LPS-induced pro-inflammatory cytokine release like IL-6, and TNF-α, as well as NO production. It displayed a significant inhibitory effect on the protein expressions such as iNOS, COX-2, NF-κB pathway like inhibitor of kappa B kinase (IKK)α/β, inhibitor of kappa B (IκB)-α and NF-κB/p65, PI3K/AKT pathway like PI3K and AKT, and MAPK pathway like c-Jun N-terminal kinase (JNK)1/2, extracellular signal-regulated kinase (ERK)1/2, and p38, in LPS-stimulated RAW264.7 macrophages. Moreover, the immunofluorescence results indicated that CPT suppressed NF-κB/p65 translocation from the cytoplasm into the nucleus. Further investigations showed that CPT treatment increased NAD(P)H quinone oxidoreductase-1 (NQO1) and heme oxygenase-1 (HO-1) expressions together with its upstream mediator, Nrf2. In addition, CPT inhibited LPS-induced toll-like receptor 4 (TLR4) and MyD88 expressions in RAW264.7 macrophages. Conclusions: Collectively, we suggested that CPT exerted significant anti-inflammatory effects via modulating TLR4-MyD88/PI3K/Nrf2 and TLR4-MyD88/NF-κB/MAPK pathways.

KeywordAnti-inflammation Cryptotanshinone Nrf2 Pi3k/akt Tlr4-myd88
URLView the original
Indexed BySCIE
WOS Research AreaIntegrative & Complementary Medicine ; Pharmacology & Pharmacy
WOS SubjectIntegrative & Complementary Medicine ; Pharmacology & Pharmacy
WOS IDWOS:000520429900001
Scopus ID2-s2.0-85082646207
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Cited Times [WOS]:13   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Corresponding AuthorGao, Hongwei; Wang, Yitao
Affiliation1.College of Pharmacy, Guangxi University of Chinese Medicine, Nanning, 530000, China
2.Guangxi Eng. Technology Research Center of Advantage Chinese Patent Drug and Ethnic Drug Development, Nanning, 530020, China
3.State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Room 1050, N22 Research Building, Macao
4.College of Pharmaceutical Science, Soochow University, Suzhou, 215123, China
Corresponding Author AffilicationInstitute of Chinese Medical Sciences
Recommended Citation
GB/T 7714
Li, Xin Xing,Zheng, Xiaoting,Liu, Zhenjie,et al. Cryptotanshinone from Salvia miltiorrhiza Bunge (Danshen) inhibited inflammatory responses via TLR4/MyD88 signaling pathway[J]. Chinese Medicine,2020,15(1).
APA Li, Xin Xing,Zheng, Xiaoting,Liu, Zhenjie,Xu, Qiongming,Tang, Hongzhen,Feng, Jianfang,Yang, Shilin,Vong, Chi Teng,Gao, Hongwei,&Wang, Yitao.(2020).Cryptotanshinone from Salvia miltiorrhiza Bunge (Danshen) inhibited inflammatory responses via TLR4/MyD88 signaling pathway.Chinese Medicine,15(1).
MLA Li, Xin Xing,et al."Cryptotanshinone from Salvia miltiorrhiza Bunge (Danshen) inhibited inflammatory responses via TLR4/MyD88 signaling pathway".Chinese Medicine 15.1(2020).
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