Dataset Information

Veronicastrum axillare Alleviates Lipopolysaccharide-Induced Acute Lung Injury via Suppression of Proinflammatory Mediators and Downregulation of the NF-?B Signaling Pathway.

ABSTRACT: Veronicastrum axillare is a traditional medical plant in China which is widely used in folk medicine due to its versatile biological activities, especially for its anti-inflammatory effects. However, the detailed mechanism underlying this action is not clear. Here, we studied the protective effects of V. axillare against acute lung injury (ALI), and we further explored the pharmacological mechanisms of this action. We found that pretreatment with V. axillare suppressed the release of proinflammatory cytokines in the serum of ALI mice. Histological analysis of lung tissue demonstrated that V. axillare inhibited LPS-induced lung injury, improved lung morphology, and reduced the activation of nuclear factor-?B (NF-?B) in the lungs. Furthermore, the anti-inflammatory actions of V. axillare were investigated in vitro. We observed that V. axillare suppressed the mRNA expression of interleukin-1? (IL-1?), IL-6, monocyte chemotactic protein-1 (MCP-1), cyclooxygenase-2 (COX-2), and tumor necrosis factor-? (TNF-?) in RAW264.7 cells challenged with LPS. Furthermore, pretreatment of V. axillare in vitro reduced the phosphorylation of p65 and I?B-? which is activated by LPS. In conclusion, our data firstly demonstrated that the anti-inflammatory effects of V. axillare against ALI were achieved through downregulation of the NF-?B signaling pathway, thereby reducing the production of inflammatory mediators.

SUBMITTER: Ma Q

PROVIDER: S-EPMC5116351 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Veronicastrum axillare Alleviates Lipopolysaccharide-Induced Acute Lung Injury via Suppression of Proinflammatory Mediators and Downregulation of the NF-κB Signaling Pathway.

Ma Quanxin Q Wang Kai K Yang Qinqin Q Ping Shun S Zhao Weichun W Shou Qiyang Q Zhou Weimin W Chen Minli M

Mediators of inflammation 20161106

Veronicastrum axillare is a traditional medical plant in China which is widely used in folk medicine due to its versatile biological activities, especially for its anti-inflammatory effects. However, the detailed mechanism underlying this action is not clear. Here, we studied the protective effects of V. axillare against acute lung injury (ALI), and we further explored the pharmacological mechanisms of this action. We found that pretreatment with V. axillare suppressed the r ...[more]

PMID: 27890971

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Project description:Nrf2 (Nuclear Factor Erythroid 2 Related Factor 2) transcription factor not only regulates oxidative stress response, but also represses inflammation by regulating cytokines production and cross-talking with NF-?B signaling pathways. Nrf2 plays an essential role in liver injury induced by oxidative stress and inflammation. Triptriolide (T11) is a minor component of Tripterygium wilfordii Hook F. (TwHF), which can be obtained by hydrolysis reaction of triptolide (T9). The major purpose of this study is to clarify the regulating effects of T11 on oxidative stress and inflammation in vivo and in vitro. LPS-stimulated RAW 264.7 cells were used to verify the regulating effects of T11 on oxidative stress (ROS and Nrf2 signaling pathway) and inflammatory cytokines production (TNF-?, IL-6 and IL-1?). The antioxidant responsive element (ARE) luciferase assay was employed to evaluate Nrf2 activation effect of T11 in HEK-293T cells. Lipopolysaccharides (LPS) induced acute liver injury (ALI) in BALB/c mice were used to study the protective effects (ALT, AST, MDA, SOD, histopathology and neutrophils/macrophages filtration) and the underlying protection mechanisms of ALI amelioration (Nrf2 and NF-?B signaling pathway) of T11. Firstly, the results showed that T11 can not only effectively decrease the productions of inflammatory cytokines (TNF-?, IL-6 and IL-1?), ROS and NO in LPS-stimulated RAW 264.7 cells, but also further significantly increase the activity of Nrf2 in HEK-293T cells. Secondly, the results suggested that T11 could dramatically decrease the oxidative stress responses (SOD and MDA) and inflammation (histopathology, neutrophils/macrophages filtration, TNF-?, IL-6 and IL-1? production) in LPS-induced ALI in BALB/c mice. Finally, the results implied that T11 could dramatically increase Nrf2 protein expression and decrease p-TAK1, p-I?B? and NF-?B protein expression both in vivo and in vitro. In conclusion, our findings indicated that T11 could alleviate LPS induced oxidative stress and inflammation by regulating Nrf2 and NF-?B signaling pathways in vitro and in vivo, which offers a novel insights for the application of TwHF in clinical.

Dataset Information

Veronicastrum axillare Alleviates Lipopolysaccharide-Induced Acute Lung Injury via Suppression of Proinflammatory Mediators and Downregulation of the NF-?B Signaling Pathway.

Publications

<i>Veronicastrum axillare</i> Alleviates Lipopolysaccharide-Induced Acute Lung Injury via Suppression of Proinflammatory Mediators and Downregulation of the NF-<i>κ</i>B Signaling Pathway.

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