Perillaldehyde Ameliorates<i>Aspergillus fumigatus</i>Keratitis by Activating the Nrf2/HO-1 Signaling Pathway and Inhibiting Dectin-1-Mediated Inflammation

Purpose To investigate the antifungal and anti-inflammatory effects of baicalein on Aspergillus fumigatus ( A. fumigatus ) keratitis and the underlying mechanisms. Methods The noncytotoxic antifungal concentration of baicalein was determined using CCK8, cell scratch assay, minimum inhibitory concentration, biofilm formation, scanning electron microscopy, propidium iodide uptake test and adherence assay in vitro and Draize test in vivo. In fungal keratitis (FK) mouse models, clinical score and plate count were used to evaluate FK severity, and myeloperoxidase assay and immunofluorescence staining were performed to examine neutrophil infiltration and activity. Real-time PCR, ELISA, and Western blot were performed to explore the anti-inflammatory activity of baicalein and the underlying mechanisms in vivo and in vitro. Results Baicalein at 0.25 mM (noncytotoxic) significantly inhibited A. fumigatus growth, biofilm formation, and adhesion in vitro. In A. fumigatus keratitis mice, baicalein mitigated FK severity, reduced fungal load, and inhibited neutrophil infiltration and activity. Baicalein not only suppressed mRNA and protein levels of proinflammatory factors IL-1β, IL-6, and TNF-α, but also inhibited the expression of thymic stromal lymphopoietin (TSLP) and TSLP receptor (TSLPR) in vivo and in vitro. In HCECs, mRNA and protein levels of IL-1β, IL-6, and TNF-α were significantly lower in the TSLP siRNA–treated group, while higher in the rTSLP-treated group than in the corresponding control. Baicalein treatment significantly inhibited rTSLP induced the expression of IL-1β, IL-6, and TNF-α. Conclusions Baicalein plays a protective role in mouse A. fumigatus keratitis by inhibiting fungal growth, biofilm formation, and adhesion, and suppressing inflammatory response via downregulation of the TSLP/TSLPR pathway.

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“…Then, the number of A. fumigatus colonies on the plate medium of the baicalein-treated group and the DMSO-treated group was counted. 44 …”

Section: Methodsmentioning

confidence: 99%

Baicalein Protects Against Aspergillus fumigatus Keratitis by Reducing Fungal Load and Inhibiting TSLP-Induced Inflammatory Response

Zhu

Peng

Zhang

et al. 2021

Invest. Ophthalmol. Vis. Sci.

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“…The primary cortical neurons were initially maintained under an anoxic (95% N 2 and 5% CO 2 ) condition to induce OGD insult in serum/glucose-free DMEM medium at 37°C for 3 h. After inducing OGD insult, the culture medium was replaced by neurobasal medium. Next, the cells were divided into separate groups including the OGD group without Lyc, the OGD + Lyc group (addition of 2.5,5,10 μM Lyc), and the OGD + Lyc + Brusatol (an Nrf2 inhibitor) group (addition of 10 μM Lyc and 100 nM Brusatol) ( Fan et al, 2020 ). The plates were then transferred to a normoxic incubator with 95% air and 5% CO 2 for 24 h.…”

Section: Methodsmentioning

confidence: 99%

Lycopene Exerts Neuroprotective Effects After Hypoxic–Ischemic Brain Injury in Neonatal Rats via the Nuclear Factor Erythroid-2 Related Factor 2/Nuclear Factor-κ-Gene Binding Pathway

Zheng

Zhu

et al. 2020

Front. Pharmacol.

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Neonatal hypoxic-ischemic encephalopathy (HIE) is a brain injury caused by perinatal asphyxia and is the main cause of neonatal death and chronic neurological diseases. Protection of neuron after hypoxic-ischemic (HI) brain injury is considered as a potential therapeutic target of HI brain injury. To date, there are no effective medicines for neonatal HI brain injury. Lycopene (Lyc), a member of the carotenoids family, has been reported to have anti-oxidative and anti-inflammatory effects. However, its effects and potential mechanisms in HI brain injury have not yet to be systematically evaluated. In this study, we investigated whether Lyc could ameliorate HI brain injury and explored the associated mechanism both in vivo and in vitro experiments. In vivo study, Lyc significantly reduced infarct volume and ameliorated cerebral edema, decreased inflammatory response, promoted the recovery of tissue structure, and improved prognosis following HI brain injury. In vitro study, results showed that Lyc reduced expression of apoptosis mediators in oxygen-glucose deprivation (OGD)-induced primary cortical neurons. Mechanistically, we found that Lyc-induced Nrf2/NF-κB pathway could partially reversed by Brusatol (an Nrf2 inhibitor), indicated that the Nrf2/NF-κB pathway was involved in the therapy of Lyc. In summary, our findings indicate that Lyc can attenuated HI brain injury in vivo and OGD-induced apoptosis of primary cortical neurons in vitro through the Nrf2/NF-κB signaling pathway.

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“…Dectin-1 can identify a variety of fungi, 167 including yeast, 168 Candida albicans , 169 , 170 Pneumocystis carinii , 171 , 172 Cryptococcus, 173 , 174 and Aspergillus. 175 , 176 The ligand of Dectin-1 is β-1,3-glucan, which can activate downstream signals through tyrosine kinase-dependent and tyrosine kinase-independent pathways after recognition and binding of the ligand. 177 , 178 Glycosylation is an important modification of the posttranslational modification of proteins (including antibodies), 179 which can significantly change the structure and function of proteins or antibodies, so it is also a key mechanism for the immune system to regulate biological activity.…”

Section: Prrs and Ligand-recognition Mechanismsmentioning

confidence: 99%

Pattern recognition receptors in health and diseases

2021

Sig Transduct Target Ther

726

515

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Pattern recognition receptors (PRRs) are a class of receptors that can directly recognize the specific molecular structures on the surface of pathogens, apoptotic host cells, and damaged senescent cells. PRRs bridge nonspecific immunity and specific immunity. Through the recognition and binding of ligands, PRRs can produce nonspecific anti-infection, antitumor, and other immunoprotective effects. Most PRRs in the innate immune system of vertebrates can be classified into the following five types based on protein domain homology: Toll-like receptors (TLRs), nucleotide oligomerization domain (NOD)-like receptors (NLRs), retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs), C-type lectin receptors (CLRs), and absent in melanoma-2 (AIM2)-like receptors (ALRs). PRRs are basically composed of ligand recognition domains, intermediate domains, and effector domains. PRRs recognize and bind their respective ligands and recruit adaptor molecules with the same structure through their effector domains, initiating downstream signaling pathways to exert effects. In recent years, the increased researches on the recognition and binding of PRRs and their ligands have greatly promoted the understanding of different PRRs signaling pathways and provided ideas for the treatment of immune-related diseases and even tumors. This review describes in detail the history, the structural characteristics, ligand recognition mechanism, the signaling pathway, the related disease, new drugs in clinical trials and clinical therapy of different types of PRRs, and discusses the significance of the research on pattern recognition mechanism for the treatment of PRR-related diseases.

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Perillaldehyde AmelioratesAspergillus fumigatusKeratitis by Activating the Nrf2/HO-1 Signaling Pathway and Inhibiting Dectin-1-Mediated Inflammation

Abstract: Perillaldehyde ameliorates aspergillus fumigatus keratitis by activating the Nrf2/HO-1 signaling pathway and inhibiting Dectin-1-mediated inflammation.

Cited by 42 publications

References 49 publications

Baicalein Protects Against Aspergillus fumigatus Keratitis by Reducing Fungal Load and Inhibiting TSLP-Induced Inflammatory Response

Baicalein Protects Against Aspergillus fumigatus Keratitis by Reducing Fungal Load and Inhibiting TSLP-Induced Inflammatory Response

Lycopene Exerts Neuroprotective Effects After Hypoxic–Ischemic Brain Injury in Neonatal Rats via the Nuclear Factor Erythroid-2 Related Factor 2/Nuclear Factor-κ-Gene Binding Pathway

Pattern recognition receptors in health and diseases

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