Isovitexin Exerts Anti-Inflammatory and Anti-Oxidant Activities on Lipopolysaccharide-Induced Acute Lung Injury by Inhibiting MAPK and NF-κB and Activating HO-1/Nrf2 Pathways

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Isoorientin Ameliorates APAP-Induced Hepatotoxicity via Activation Nrf2 Antioxidative Pathway: The Involvement of AMPK/Akt/GSK3β

Oxidative stress has been highlighted as therapeutic targets for acetaminophen (APAP)-induced hepatotoxicity. Isoorientin (Iso), a well-known flavonoid-like compound, has been shown to have antioxidant potential. However, the effect of Iso on APAP-induced liver injury has not yet been elucidated. The present study investigated the hepatoprotective effect of Iso and its underlying mechanism. C57BL/6J mice were used to evaluate the hepatoprotective effect of Iso in vivo and HepG2 cells were utilized to further decipher the mechanisms of Iso -induced Nrf2 activation. We found that Iso treatment significantly reduced APAP-induced hepatotoxicity by reducing the lethality, histopathological liver changes, and alanine transaminase (ALT) and aspartate aminotransferase (AST) levels in serum. These effects were accompanied by decreased malondialdehyde (MDA) formation and myeloperoxidase level (MPO), and by decreased superoxide dismutase (SOD) and glutathione (GSH) depletion. Moreover, Iso induced Nrf2 activation and translocation as well as upstream AMPK/Akt/GSK3β activation. Furthermore, Iso effectively alleviated mitochondrial dysfunction by reducing c-jun N-terminal kinase phosphorylation and translocation, Bax mitochondrial translocation, and apoptosis-inducing factor and cytochrome c release. Further mechanistic investigations revealed that the activation of Nrf2 by Iso via the AMPK/Akt/GSK3β pathway contributed to the hepatoprotective activity of Iso in vitro. In addition, the Iso-mediated inhibition of APAP-induced the lethality, histopathological changes and mitochondrial dysfunction observed in WT mice was nearly absent in Nrf2-/- mice. In summary, Iso ameliorated APAP-induced hepatotoxicity by activating Nrf2 via the AMPK/Akt/GSK3β pathway

Pterostilbene Activates the Nrf2-Dependent Antioxidant Response to Ameliorate Arsenic-Induced Intracellular Damage and Apoptosis in Human Keratinocytes

The NF-E2 p45-related factor 2 (Nrf2), a transcription factor that regulates the cellular adaptive response to oxidative stress, is a target for limiting tissue damage from exposure to environmental toxins, including arsenic. In the current study, we determine whether Pterostilbene (Pts), as a potent activator of Nrf2, has a protective effect on arsenic-induced cytotoxicity and apoptosis in human keratinocytes. Human keratinocytes (HaCaT) or mouse epidermal cells (JB6) were pretreated with Pts for 24 h prior to arsenic treatment. Harvested cells were analyzed by MTT, DCFH-DA, commercial kits, Flow cytometry assay and western blot analysis. Our results demonstrated that Pts effectively regulated the viability in HaCaT and JB6 cells, decreased the reactive oxygen species (ROS) generation and lipid peroxidation (MDA), and improved the NaAsO2-induced depletion of superoxide dismutase (SOD). Moreover, Pts treatment further dramatically inhibited NaAsO2-induced apoptosis, specifically the mitochondrial mediation of apoptosis, which coincided with the effective recovery of NaAsO2-induced mitochondrial membrane potential (ΔΨm) depolarization and cytochrome c release from the mitochondria. Furthermore, arsenic-induced decrease of anti-apoptotic factor Bcl-2 and Bcl-xl, and increase of pro-apoptotic factor Bax and Bad, as well as survival signal related factor caspase 3 activation were reversed by Pts treatment. Further mechanistic studies confirmed that Pts increased antioxidant enzyme expression in a dose-dependent manner, which was related to Nrf2 nuclear translocation. In addition, the effects of Pts on NaAsO2-induced cell viability were largely weakened when Nrf2 was knocked down. Together, our results provide evidence for the use of Pts to activate the Nrf2 pathway to alleviate arsenic-induced dermal damage

Asiatic Acid Exhibits Anti-inflammatory and Antioxidant Activities against Lipopolysaccharide and d-Galactosamine-Induced Fulminant Hepatic Failure

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 O2−), 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

Two-step fabrication of nanoporous copper films with tunable morphology for SERS application

peer-reviewedIt is important to design and fabricate nanoporous metals (NPMs) with optimized microstructures for specific applications. In this contribution, nanoporous coppers (NPCs) with controllable thicknesses and pore sizes were fabricated via the combination of a co-sputtering of Cu/Ti with a subsequent dealloying process. The effect of dealloying time on porous morphology and the corresponding surface enhanced Raman scattering (SERS) behaviors were systematically investigated. Transmission electron microscopy (TEM) identified the presences of the gaps formed between ligaments and also the nanobumps on the nanoparticle-aggregated ligament surface, which were likely to contribute as the “hot spots” for electromagnetic enhancement. The optimal NPC film exhibited excellent SERS performance towards Rhodamine 6G (R6G) with a low limiting detection (10−9 M), along with good uniformity and reproducibility. The calculated enhancement factor of ca. 4.71 × 107 was over Au substrates and comparable to Ag systems, promising the proposed NPC as a cheap candidate for high-performance SERS substrate

Different Effects of Farrerol on an OVA-Induced Allergic Asthma and LPS-induced Acute Lung Injury

BACKGROUND: Farrerol, isolated from rhododendron, has been shown to have the anti-bacterial activity, but no details on the anti-inflammatory activity. We further evaluated the effects of this compound in two experimental models of lung diseases. METHODOLOGY/PRINCIPAL FINDINGS: For the asthma model, female BALB/c mice were challenged with ovalbumin (OVA), and then treated daily with farrerol (20 and 40 mg/kg, i.p.) as a therapeutic treatment from day 22 to day 26 post immunization. To induce acute lung injury, female BALB/c mice were injected intranasally with LPS and treated with farrerol (20 and 40 mg/kg, i.p.) 1 h prior to LPS stimulation. Inflammation in the two different models was determined using ELISA, histology, real-time PCR and western blot. Farrerol significantly regulated the phenotype challenged by OVA, like cell number, Th1 and Th2 cytokines levels in the BALF, the OVA-specific IgE level in the serum, goblet cell hyperplasia in the airway, airway hyperresponsiveness to inhaled methacholine and mRNA expression of chemokines and their receptors. Furthermore, farrerol markedly attenuated the activation of phosphorylation of Akt and nuclear factor-κB (NF-κB) subunit p65 both in vivo and in vitro. However, farrerol has no effect on the acute lung injury model. CONCLUSION/SIGNIFICANCE: Our finding demonstrates that the distinct anti-inflammatory effect of farrerol in the treatment of asthma acts by inhibiting the PI3K and NF-κB pathway