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Isoliquiritigenin attenuates LPS-induced AKI by suppression of inflammation involving NF-?B pathway.

ABSTRACT: Septic acute kidney injury (AKI) characterized as acute infection and renal inflammation, still lacks of effective therapies. Isoliquiritigenin (ISL) as a small molecular from licorice, is able to inhibit the expression of HMGB1. However, the role and mechanism of ISL in septic AKI has not been investigated. In this study, we used LPS injection to induce murine septic AKI. One hour before LPS injection, 50 mg/kg ISL was once orally given to the mice. For the in vitro study, HK2 human tubular cells were respectively treated with 50 ?M and 100 ?M ISL 5 hrs before 2 ?g/ml LPS stimulation. Then we observed that ISL ameliorated renal dysfunction and attenuated renal tubular injury. ISL inhibited the phosphorylation of I?B-? and NF-?B p65 after LPS induction both in vivo and in vitro. ISL also inhibited NF-?B p65 translocation from cytoplasm to the nucleus upon LPS stimulation. Further, NF-?B p65 translocation could trigger macrophage polarization, neutrophil activation and pro-inflammatory cytokines secretion in LPS-induced inflammation. These results showed that ISL could alleviate LPS-induced AKI by suppressing NF-?B p65 translocation and inhibiting inflammatory responses, indicating protective effects of ISL in LPS-induced acute renal inflammation. This study might be useful for designing potential clinical trials to prevent and treat sepsis induced AKI in patients with serious illness.

SUBMITTER: Tang Y

PROVIDER: S-EPMC6325500 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Isoliquiritigenin attenuates LPS-induced AKI by suppression of inflammation involving NF-κB pathway.

Tang Yun Y Wang Chan C Wang Yanmei Y Zhang Jiong J Wang Fang F Li Li L Meng Xianglong X Li Guisen G Li Yi Y Wang Li L

American journal of translational research 20181215 12

Septic acute kidney injury (AKI) characterized as acute infection and renal inflammation, still lacks of effective therapies. Isoliquiritigenin (ISL) as a small molecular from licorice, is able to inhibit the expression of HMGB1. However, the role and mechanism of ISL in septic AKI has not been investigated. In this study, we used LPS injection to induce murine septic AKI. One hour before LPS injection, 50 mg/kg ISL was once orally given to the mice. For the <i>in vitro</i> study, HK<sub>2</sub> ...[more]

PMID: 30662657

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Project description:BackgroundDocosahexaenoic acid (DHA) and DHA-derived lipid mediators have recently been shown to possess anti-inflammatory and pro-resolving properties. In fact, DHA can down-regulate lipolysaccharide (LPS)-induced activation of NF-κB via a PPARγ-dependent pathway. We sought to investigate the effects of the novel DHA-derived mediator resolvin D1 (RvD1) on LPS-induced acute lung injury and to determine whether these effects occur via a PPARγ-dependent pathway.MethodsBALB/c mice aged 6-8 weeks were randomly divided into seven groups: two control groups receiving saline or RvD1 (600 ng) without LPS; a control group receiving LPS only; an experimental group receiving RvD1 (300 ng) or RvD1 (600 ng), followed by LPS; a group receiving the PPARγ antagonist GW9662; and a group receiving GW9662, then RvD1 (600 ng) and finally LPS. LPS (50 μM) and saline were administered intratracheally. RvD1 was injected intravenously 24 h and 30 min before LPS, while GW9662 was injected intravenously 30 min before RvD1. Mice were killed at 6, 12, and 24 h. Samples of bronchoalveolar lavage fluid (BALF) were analyzed for cell counts and cytokine analysis. Lung tissues were collected for histology, Western blotting and electrophoretic mobility shift assays (EMSAs).ResultsAt all three time points, groups receiving either dose of RvD1 followed by LPS had significantly lower total leukocyte counts and levels of TNF-α and IL-6 levels in BALF than did the group given only LPS. RvD1 markedly attenuated LPS-induced lung inflammation at 24 h, based on hematoxylin-eosin staining of histology sections. RvD1 activated PPARγ and suppressed IκBα degradation and NF-κB p65 nuclear translocation, based on Western blots and EMSAs. The PPARγ inhibitor GW9662 partially reversed RvD1-induced suppression of IκBα degradation and p65 nuclear translocation.ConclusionsThese results suggest that RvD1 may attenuate lung inflammation of LPS-induced acute lung injury by suppressing NF-κB activation through a mechanism partly dependent on PPARγ activation.

Project description:ObjectivesBiosurfactants with anti-inflammatory activity may alleviate skin irritation caused by synthetic surfactants in cleaning products. Sophorolipid (SL) is a promising alternative to synthetic surfactants. However, there are few reports on the anti-inflammatory activity of SL and the underlying mechanism. The purpose of this work is to verify that lipopolysaccharide (LPS)-induced inflammation could be inhibited through targeting the pathway of nuclear factor-κB (NF-κB) in RAW264.7 cells.MethodsThe influence of SL on cytokine release was investigated by LPS-induced RAW264.7 cells using ELISA. The quantification of the protein expression of corresponding molecular markers was realized by Western blot analysis. Flow cytometry was employed to determine the levels of Ca2+ and reactive oxygen species (ROS). The relative expression of inducible nitric oxide synthase (INOS) and cyclooxygenase-2 (COX-2) was determined by RT-PCR. An immunofluorescence assay and confocal microscope were used to observe the NF-κB/p65 translocation from the cytoplasm into the nucleus. The likely targets of SL were predicted by molecular docking analysis.ResultsSL showed anti-inflammatory activity and reduced the release of inflammatory cytokines including interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and nitric oxide (NO). The experimental results show that SL suppressed the Ca2+ and ROS levels influx in the LPS-induced RAW264.7 cells and alleviated the LPS-induced expression of iNOS and COX-2, the LPS-induced translocation of NF-κB (p65) from the cytoplasm into the nucleus, and the expression of phosphorylated proteins such as p65 and IκBα. Furthermore, molecular docking analysis showed that SL may inhibit inflammatory signaling by competing with LPS to bind TLR4/MD-2 through hydrophobic interactions and by inhibiting IKKβ activation through the hydrogen bonding and hydrophobic interactions.ConclusionThis study demonstrated that SL exerted anti-inflammatory activity via the pathway of NF-κB in RAW264.7 cells.

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Isoliquiritigenin attenuates LPS-induced AKI by suppression of inflammation involving NF-?B pathway.

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Isoliquiritigenin attenuates LPS-induced AKI by suppression of inflammation involving NF-κB pathway.

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