Dataset Information

Triptriolide Alleviates Lipopolysaccharide-Induced Liver Injury by Nrf2 and NF-?B Signaling Pathways.

ABSTRACT: 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.

SUBMITTER: Yang YQ

PROVIDER: S-EPMC6124152 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Triptriolide Alleviates Lipopolysaccharide-Induced Liver Injury by Nrf2 and NF-κB Signaling Pathways.

Yang Yi-Qi YQ Yan Xiao-Teng XT Wang Kai K Tian Rui-Min RM Lu Zhao-Yu ZY Wu Li-Lan LL Xu Hong-Tao HT Wu Yun-Shan YS Liu Xu-Sheng XS Mao Wei W Xu Peng P Liu Bo B

Frontiers in pharmacology 20180829

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-κB signaling pathways. Nrf2 plays an essential role in liver injury induced by oxidative stress and inflammation. Triptriolide (T11) is a minor component of <i>Tripterygium wilfordii</i> Hook F. (TwHF), which can be obtained by hydrolysis reaction of triptolide (T9). The major purpose of ...[more]

PMID: 30210350

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Project description:Pterostilbene (PTER) is a kind of stilbene compound with biological activity isolated from plants such as red sandalwood, blueberry and grape. It has anti-tumor, anti-bacterial, anti-oxidation and other pharmacological activities. However, the underlying mechanism of the protective effect of PTER on lipopolysaccharide (LPS)-induced acute lung injury (ALI) remained not clarified. In this study, LPS was used to establish a mouse model of ALI. Bronchoalveolar lavage fluid (BALF) was collected for inflammatory cells, and the wet-to-dry weight ratio of the lungs was measured. The activities of myeloperoxidase (MPO), antioxidant indexes such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and oxidation index such as malondialdehyde (MDA) in lung tissues of mice were measured by the corresponding kits. The levels of Cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), TNF-α, IL-6 and IL-1β in lung tissues of mice were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The activities of Nrf2, HO-1, p-p65 and p-IκB were determined by western blotting. The results showed that the model of LPS-induced ALI was successfully replicated, and it was found that PTER could significantly improve the pathological degree of ALI such as sustained the integrity of the lung tissue structure, alleviated pulmonary interstitial edema and alveolar wall thickening, reduced infiltrated inflammatory cells. PTER could decrease the number of inflammatory cells and obviously inhibit the increase of W/D ratio caused by LPS. PTER could also significantly reduce LPS-induced MPO and MDA, and increase LPS-decreased SOD, CAT and GSH-Px in the lungs. In addition, it was also found that PTER has the ability to decrease LPS-induced production of COX-2, iNOS, TNF-α, IL-6 and IL-1β. The underlying mechanism involved in the protective effect of PTER on ALI were via activating Nrf2 and HO-1, and inhibiting the phosphorylation of p65 and IκB. These results suggested that PTER can protect LPS-induced ALI in mice by inhibiting inflammatory response and oxidative stress, which provided evidence that PTER may be a potential therapeutic candidate for LPS-induced ALI intervention.

Dataset Information

Triptriolide Alleviates Lipopolysaccharide-Induced Liver Injury by Nrf2 and NF-?B Signaling Pathways.

Publications

Triptriolide Alleviates Lipopolysaccharide-Induced Liver Injury by Nrf2 and NF-κB Signaling Pathways.

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