Dihydrotanshinone exhibits an anti-inflammatory effect in vitro and in vivo through blocking TLR4 dimerization

Yuan, Renyikun; Huang, Liting; Du, Lijun; Jiao, Feng; Li, Jun; Luo, Yingying; Xu, Qiong; Yang, Shilin; Feng, Yulin

doi:10.1016/j.phrs.2019.02.017

Cited by 69 publications

(58 citation statements)

References 45 publications

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“…MyD88, the downstream protein of TLR4, is often needed to activate TAK1. Subsequently, NF-κB and MAPK pathways are activated during inflammatory processes [4,42]. Our results showed that CPT reduced the protein expressions of TLR4 and MD2 in LPS-stimulated macrophages.…”

Section: Discussionmentioning

confidence: 58%

“…The flow cytometric analyses of the measurement of NO and calcium levels were performed as previously described [4]. Briefly, 2 × 10 5 RAW264.7 cells were seeded onto 24-well plates and cultured overnight.…”

Section: Flow Cytometry Assay For the Measurement Of Nitric Oxide (Nomentioning

confidence: 99%

“…When LPS is released from the bacterial membrane, it will be sensed by the TLR4-MD-2 heterodimer [4,5]. The TLR4 heterodimer will then recruit the downstream protein MyD88, which is often needed to activate NF-κB and MAPK pathways during inflammatory processes [5,7].…”

Section: Cpt Exerted Anti-inflammatory Effects Via Inhibiting Tlr4/ Mmentioning

confidence: 99%

“…It is beneficial for the treatment of inflammatory-related diseases to clearly understand the mechanisms of inflammation [2,3]. Toll-like receptor-4 (TLR4), one of the best characterized pattern recognition receptors, is highly related to inflammatory responses [4]. It forms a heterodimer with MD-2 that recognizes lipopolysaccharide (LPS) [5].…”

Section: Introductionmentioning

confidence: 99%

“…In macrophages, calcium, as a second signal messenger, plays an important role in the activation of macrophages, such as transcriptional control, and the activation of kinases, and phosphatases [4,14]. An increase in intracellular Ca 2+ in accordance with LPS stimulation has been shown to be involved in the inflammatory process for the transcriptional activation, and leads to TNF-α, IL-6, IL-1β, and NO release [4,14].…”

Section: Introductionmentioning

confidence: 99%

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Cryptotanshinone from Salvia miltiorrhiza Bunge (Danshen) inhibited inflammatory responses via TLR4/MyD88 signaling pathway

Zheng

Liu

et al. 2020

Chin Med

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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. © The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article' s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article' Conclusions: Collectively, we suggested that CPT exerted s...

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Section: Discussionmentioning

confidence: 58%

Section: Flow Cytometry Assay For the Measurement Of Nitric Oxide (Nomentioning

confidence: 99%

Section: Cpt Exerted Anti-inflammatory Effects Via Inhibiting Tlr4/ Mmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Cryptotanshinone from Salvia miltiorrhiza Bunge (Danshen) inhibited inflammatory responses via TLR4/MyD88 signaling pathway

Zheng

Liu

et al. 2020

Chin Med

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Rotundic acid reduces LPS‐induced acute lung injury in vitro and in vivo through regulating TLR4 dimer

Yuan

Wang

et al. 2021

Phytotherapy Research

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Acute lung injury (ALI) is a serious clinical disease. Rotundic acid (RA), a natural ingredient isolated from Ilex rotunda Thunb, exhibits multiple pharmacological activities. However, RA's therapeutic effect and mechanism on ALI remain to be elucidated. The present study aimed to further clarify its regulating effects on inflammation in vitro and in vivo. Our results indicated that RA significantly inhibited the overproduction of interleukin‐6 (IL‐6), tumor necrosis factor‐α (TNF‐α), cyclooxygenase‐2 (COX‐2), and inducible nitric oxide synthase (iNOS). RA decreased ROS production and calcium influx. In addition, RA inhibited the activation of PI3K, MAPK, and NF‐κB pathways and enhanced the activity of nuclear factor E2‐related factor 2 (Nrf2) signaling. The cellular thermal shift assay and docking results indicated that RA bind to TLR4 to block TLR4 dimerization. Furthermore, RA pretreatment effectively inhibited ear edema induced by xylene and LPS‐induced endotoxin death and had a protective effect on LPS‐induced ALI. Our findings collectively indicated that RA has anti‐inflammatory effects, which may serve as a potential therapeutic option for pulmonary inflammation.

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Synthesis of 2,3‐dihydrofurans via Lewis acid‐Catalyzed [4+1] Cycloaddition of Enynones with Sulfoxonium Ylides in Ionic Liquids: A Mild and Green Platform

Ding

Chen

et al. 2020

ChemistrySelect

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The zinc‐catalyzed [4+1] cycloadddition followed by intramolecular insertion reaction between enynones and sulfoxonium ylides for the synthesis of multisubstituted 2,3‐dihydrofurans in ionic liquids is described. This highly efficient and step‐economical reaction displays excellent functional group compatibility and stereoselectivity. The reaction media colud maintain high reaction activity even after six cycles.

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Dihydrotanshinone exhibits an anti-inflammatory effect in vitro and in vivo through blocking TLR4 dimerization

Cited by 69 publications

References 45 publications

Cryptotanshinone from Salvia miltiorrhiza Bunge (Danshen) inhibited inflammatory responses via TLR4/MyD88 signaling pathway

Cryptotanshinone from Salvia miltiorrhiza Bunge (Danshen) inhibited inflammatory responses via TLR4/MyD88 signaling pathway

Rotundic acid reduces LPS‐induced acute lung injury in vitro and in vivo through regulating TLR4 dimer

Synthesis of 2,3‐dihydrofurans via Lewis acid‐Catalyzed [4+1] Cycloaddition of Enynones with Sulfoxonium Ylides in Ionic Liquids: A Mild and Green Platform

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