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Indirubin improves antioxidant and anti-inflammatory functions in lipopolysaccharide-challenged mice.

ABSTRACT: Indirubin, a traditional Chinese medicine formulation from the Muricidae family, has been reported to exhibit abroad anti-cancer and anti-inflammation activities and mediate nuclear factor-?B (NF-?B) signal. Thus, this study aimed to investigate the protective effects of indirubin on LPS-induced acute lung injury and the potential mechanism in mice. The results showed that LPS treatment caused oxidative stress and inflammation in mice. Indirubin alleviated LPS-caused oxidative stress and inflammation via reducing MDA abundance and IL-1? and TNF-? expressions in mice. Meanwhile, indirubin improved lung NO production and inhibited NF-?B activation caused by LPS exposure. In conclusion, indirubin alleviated LPS-induced acute lung injury via improving antioxidant and anti-inflammatory functions, which might be associated with the NO and NF-?B signals.

SUBMITTER: Qi T

PROVIDER: S-EPMC5482685 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Indirubin improves antioxidant and anti-inflammatory functions in lipopolysaccharide-challenged mice.

Qi Tianjie T Li Haitao H Li Shuai S

Oncotarget 20170501 22

Indirubin, a traditional Chinese medicine formulation from the Muricidae family, has been reported to exhibit abroad anti-cancer and anti-inflammation activities and mediate nuclear factor-κB (NF-κB) signal. Thus, this study aimed to investigate the protective effects of indirubin on LPS-induced acute lung injury and the potential mechanism in mice. The results showed that LPS treatment caused oxidative stress and inflammation in mice. Indirubin alleviated LPS-caused oxidative stress and inflamm ...[more]

PMID: 28525368

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Project description:Lipopolysaccharides (LPS) induces liver inflammatory response by activating the TLR4/NF-κB signaling pathway. Antrodia cinnamomea polysaccharide (ACP) is a medicinal mushroom that can protect from intoxication, liver injury, and inflammation. Nevertheless, the effect of ACP on the liver antioxidant, anti-inflammatory capacity and cecal flora structure of LPS-challenged broilers remains unclear. The aim of this experiment was to investigate the effects of ACP on the anti-oxidative and anti-inflammatory capacities of the liver, and cecal microbiota in slow-growing broilers stimulated by LPS. A total of 750 slow-growing broilers (9-day-old) were assigned to five treatments with 6 replicates of 25 chicks per replicate: a control diet, the chicks were fed a control diet and challenged with LPS. Dietary treatments 3 to 5 were the control diet supplemented with 100, 200, 400 mg/kg ACP challenged with LPS, respectively. The groups of 100 mg/kg ACP supplementation significantly increased liver index, pancreas index, and bursa of Fabricius index (P < 0.05). The GSH-Px content of LPS-challenged broilers was lower than that of the control group (P < 0.001), but the content of MDA increased (P < 0.001). Feeding with 100 mg/kg ACP resulted in increased the activity of T-AOC, GSH-Px, and T-SOD, and decreased MDA content (P < 0.05). The activity of TNF-α, IL-1β, and IL-6 of the LPS group increased, but these indicators were decreased with supplemental 100 mg/kg ACP (P < 0.05). Dietary application of ACP up to 100 mg/kg down-regulated (P < 0.05) the expression of TLR4/NF-κB pathway in the liver induced by LPS. The results of 16S rRNA demonstrated that feeding with 100 mg/kg ACP can change the diversity and composition of the gut microbiota, and restrained the decline of beneficial cecal microbiota (typically Lactobacillus, Faecalibacterium, and Christensenellaceae R-7 group) in the challenged LPS group (P < 0.05). Conclusively, feeding a diet with 100 mg/kg ACP may have beneficial effects on liver damage and the bacterial microbiota diversity and composition in the ceca of LPS-stressed slow-growing broiler breeds, probably because of its combined favorable effects on antioxidants and cytokines contents, and restoration the decline of beneficial cecal microbiota.

Project description:Background:Sepsis-induced cardiomyopathy (SIC) is a common severe complication of sepsis that contributes to mortality. SIC is closely associated with excessive inflammatory responses, failed inflammation resolution, and apoptotic damage. Resolvin E1 (RvE1), an omega-3 polyunsaturated fatty acid (PUFA)-derived metabolite, has been reported to exert anti-inflammatory or proresolving activity in multiple animal models of inflammatory disease. However, the therapeutic potential of RvE1 in SIC remains undetermined, which was, therefore, the aim of the present study. Methods:C57BL/6J mice were randomly divided into three groups: control, lipopolysaccharide (LPS), and LPS + RvE1. Echocardiography, Western blotting (WB), quantitative real-time (QRT)-PCR, histological analyses, and flow cytometry were used to evaluate cardiac function, myocardial inflammation, and the underlying mechanisms. Results:The RvE1-injected group showed improved left ventricular (LV) function and reduced serum lactate dehydrogenase (LDH) and creatine kinase myocardial bound (CK-MB) levels. Compared to LPS treatment alone, RvE1 treatment inhibited the infiltration of neutrophils and macrophages into the heart and spleen and suppressed the secretion of pro-inflammatory cytokines, including interleukin (IL)-1?, IL-6, and monocyte chemoattractant protein (MCP)-1, in the heart. We also observed that the activation of the mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-?B signaling pathways was blocked by RvE1 treatment, and this inhibition contributed to the improvement in the inflammatory response induced by LPS. RvE1 inhibited LPS-induced M1 macrophage polarization and promoted macrophage polarization toward the M2-like phenotype in both the heart and spleen. In addition, LPS administration dysregulated cyclooxygenase (COX) and lipoxygenase (LOX) in the heart, which were rectified by RvE1 treatment. RvE1 also reduced myocardial apoptosis rate in response to LPS-induced heart injury. Conclusion:RvE1 protects the heart against SIC possibly through the inhibition of the MAPK and NF-?B inflammatory signaling pathways, modulation of macrophage polarization, and reduction in myocardial apoptosis. RvE1 may be a novel lipid mediator for the treatment of SIC.

Project description:Inflammation and oxidative stress are essential for the pathogenesis of fulminant hepatic failure (FHF). Asiatic acid (AA), which is a pentacyclic triterpene that widely occurs in various vegetables and fruits, has been reported to possess antioxidant and anti-inflammatory properties. In this study, we investigated the protective effects of AA against lipopolysaccharide (LPS) and d-galactosamine (GalN)-induced FHF and the underlying molecular mechanisms. Our findings suggested that AA treatment effectively protected against LPS/d-GalN-induced FHF by lessening the lethality; decreasing the alanine transaminase and aspartate aminotransferase levels, interleukin (IL)-1β, IL-6, and tumor necrosis factor-α production, malondialdehyde formation, myeloperoxidase level and reactive oxygen species generation (i.e., H2O2, NO, and [Formula: see text]), and increasing the glutathione and superoxide dismutase contents. Moreover, AA treatment significantly inhibited mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) signaling pathway activation via the partial induction of programmed cell death 4 (PDCD4) protein expressions, which are involved in inflammatory responses. Furthermore, AA treatment dramatically induced the expression of the glutamate-cysteine ligase modifier subunit, the glutamate-cysteine ligase catalytic subunit, heme oxygenase-1, and NAD (P) H: quinoneoxidoreductase 1 (NQO1), which are largely dependent on activation of the nuclear factor-erythroid 2-related factor 2 (Nrf2) through the induction of AMP-activated protein kinase (AMPK) and glycogen synthase kinase-3β (GSK3β) phosphorylation. Accordingly, AA exhibited protective roles against LPS/d-GalN-induced FHF by inhibiting oxidative stress and inflammation. The underlying mechanism may be associated with the inhibition of MAPK and NF-κB activation via the partial induction of PDCD4 and upregulation of Nrf2 in an AMPK/GSK3β pathway activation-dependent manner.

Project description:This study aimed to evaluate the effects of maternal nucleotide (NT) supplementation on intestinal morphology and immune function in lipopolysaccharide-challenged newborn piglets. At 85 d gestation, 12 sows were selected and assigned to two groups: the CON group (basal diet, n = 6) and the NT group (basal diet with 1 g/kg NT mixture, n = 6). After parturition, newborn piglets were collected without suckling. Piglets from the CON group were intraperitoneally injected with sterile saline or lipopolysaccharide (LPS, 10 mg/kg body weight), and divided into the C-CON (n = 6) and C-LPS groups (n = 6). Piglets from the NT group received the same treatment and were divided into the N-CON (n = 6) and N-LPS groups (n = 6). The blood and small intestinal samples of piglets were collected 1 h after injection. The results showed that: (1) maternal NT supplementation increased the concentrations of serum complement C3 and C4 (P < 0.05), and suppressed the increase in serum hypersensitive C-reactive protein in LPS-challenged newborn piglets (P < 0.05); (2) maternal NT supplementation increased the villus height and the ratio of villus height to crypt depth in the duodenum of newborn piglets (P < 0.05) and inhibited the LPS-induced decrease in the villus height in the jejunum and ileum (P < 0.05). (3) The LPS-induced increased levels of interleukin-6 in the jejunum and tumor necrosis factor-α in the ileum of newborn piglets were suppressed by maternal NT supplementation (P < 0.05). (4) In the jejunum of newborn piglets, maternal NT supplementation inhibited the LPS-induced increase in toll-like receptor 4 (TLR4) mRNA and protein expression (P < 0.05) and the decrease of nuclear factor-κB inhibitor α (IκBα) protein expression (P < 0.05). In the ileum, piglets had a lower nuclear factor-κB (NFκB) mRNA expression in the NT groups than the CON groups (P < 0.05), and maternal NT supplementation suppressed the decrease of IκBα mRNA in LPS-treated piglets (P < 0.05). In conclusion, maternal NT supplementation could promote the intestinal development and immune function of newborn piglets, and may improve LPS-induced intestinal inflammatory responses via the TLR4/IκBα/NFκB pathway.

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Indirubin improves antioxidant and anti-inflammatory functions in lipopolysaccharide-challenged mice.

Publications

Indirubin improves antioxidant and anti-inflammatory functions in lipopolysaccharide-challenged mice.

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