Nonerythropoietic Erythropoietin Mimetic Peptide ARA290 Ameliorates Chronic Stress-Induced Depression-Like Behavior and Inflammation in Mice

Xu, Guizhou; Zou, Tao; Deng, Lijiao; Yang, Guang; Guo, Tingting; Wang, Yi; Niu, Chunxiao; Cheng, Qianqian; Yang, Xiqin; Dong, Jie; Zhang, Jiyan

doi:10.3389/fphar.2022.896601

Cited by 7 publications

(5 citation statements)

References 55 publications

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“…21 As anticipated, this study revealed no significant changes in peripheral blood erythropoietic parameters, serum AST, ALT, LDH, and spleen weight and length after ARA290 treatment. As mentioned earlier, the anti-apoptotic and anti-inflammatory activities of ARA290 have been confirmed by previous studies in various models, 22,23 and our results further demonstrated that these ARA290 effects extend to cerebral ischemic models. Untargeted LC-MS/MS analyses revealed that the primary differential metabolites affected by ARA290 were associated with the pathophysiology of the vascular endothelium, which may be related to its anti-apoptotic and anti-inflammatory properties.…”

Section: Temporal Changes In β Cr Protein Levels Are Related To Degre...supporting

confidence: 91%

Erythropoietin‐derived peptide ARA290 mediates brain tissue protection through the β‐common receptor in mice with cerebral ischemic stroke

Wang,

Yang,

Huang

et al. 2024

CNS Neurosci Ther

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AimTo explore the neuroprotective effects of ARA290 and the role of β‐common receptor (βCR) in a mouse model of middle cerebral artery occlusion (MCAO).MethodsThis study included male C57BL/6J mice that underwent MCAO and reperfusion. The neuroprotective effect of ARA290 on MCAO‐induced brain injury was investigated using neurological function tests (Longa and modified neurological severity score). Cerebral infarction was examined by 2, 3, 5‐triphenyl tetrazolium chloride staining, neuronal apoptosis was assessed by immunofluorescence staining, blood parameters were measured using a flow cytometry‐based automated hematology analyzer, liquid chromatography with tandem mass spectrometry was used to identify the serum metabolomics signature, inflammatory cytokines and liver index were detected by commercially available kits, and the protein levels of the erythropoietin (EPO) receptor and βCR were measured by western blot.ResultsARA290 exerted a qualitatively similar neuroprotective effect after MCAO as EPO. ARA290 significantly reduced neuronal apoptosis and the level of inflammatory cytokines in the brain tissue. However, ARA290's neuroprotective effect was significantly suppressed following the injection of siRNA against βCR.ConclusionARA290 provided a neuroprotective effect via βCR in cerebral ischemic mice without causing erythropoiesis. This study provides novel insights into the role of ARA290 in ischemic stroke intervention.

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Section: Temporal Changes In β Cr Protein Levels Are Related To Degre...supporting

confidence: 91%

Erythropoietin‐derived peptide ARA290 mediates brain tissue protection through the β‐common receptor in mice with cerebral ischemic stroke

Wang,

Yang,

Huang

et al. 2024

CNS Neurosci Ther

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“…Moreover, a study conducted by Xu et al further validated the anti-inflammatory effect of ARA290. Daily administration of ARA290 could ameliorate depression-like behavior during chronic stress induction in mouse models via reducing neutrophils in the bone marrow and meninges [25]. Here, we tested the efferocytosis ability of Pg.…”

Section: Discussionmentioning

confidence: 99%

The Role of Macrophage Efferocytosis in the Pathogenesis of Apical Periodontitis

Guan,

Wang,

et al. 2024

IJMS

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Macrophages (Mφs) play a crucial role in the homeostasis of the periapical immune micro-environment caused by bacterial infection. Mφ efferocytosis has been demonstrated to promote the resolution of multiple infected diseases via accelerating Mφ polarization into M2 type. However, the Mφ efferocytosis–apical periodontitis (AP) relationship has not been elucidated yet. This study aimed to explore the role of Mφ efferocytosis in the pathogenesis of AP. Clinical specimens were collected to determine the involvement of Mφ efferocytosis in the periapical region via immunohistochemical and immunofluorescence staining. For a further understanding of the moderator effect of Mφ efferocytosis in the pathogenesis of AP, both an in vitro AP model and in vivo AP model were treated with ARA290, a Mφ efferocytosis agonist. Histological staining, micro-ct, flow cytometry, RT-PCR and Western blot analysis were performed to detect the inflammatory status, alveolar bone loss and related markers in AP models. The data showed that Mφ efferocytosis is observed in the periapical tissues and enhancing the Mφ efferocytosis ability could effectively promote AP resolution via facilitating M2 Mφ polarization. Collectively, our study demonstrates the functional importance of Mφ efferocytosis in AP pathology and highlights that accelerating Mφ efferocytosis via ARA290 could serve as an adjuvant therapeutic strategy for AP.

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“…EPO and non-erythropoietic derivatives have also shown potential pro-cognitive effects in psychiatric disorders [ 60 ]. The non-erythropoietic derivative ARA290 can reduce inflammation and depression, which prolongs stress in rodents [ 61 ]. Studies have found that MDD may be related to neuronal plasticity damage8.…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics and systems biology approach to identify the pathogenetic link of neurological pain and major depressive disorder

Hu,

Fu,

Cai

et al. 2024

Exp. Biol. Med.

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Neurological pain (NP) is always accompanied by symptoms of depression, which seriously affects physical and mental health. In this study, we identified the common hub genes (Co-hub genes) and related immune cells of NP and major depressive disorder (MDD) to determine whether they have common pathological and molecular mechanisms. NP and MDD expression data was downloaded from the Gene Expression Omnibus (GEO) database. Common differentially expressed genes (Co-DEGs) for NP and MDD were extracted and the hub genes and hub nodes were mined. Co-DEGs, hub genes, and hub nodes were analyzed for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment. Finally, the hub nodes, and genes were analyzed to obtain Co-hub genes. We plotted Receiver operating characteristic (ROC) curves to evaluate the diagnostic impact of the Co-hub genes on MDD and NP. We also identified the immune-infiltrating cell component by ssGSEA and analyzed the relationship. For the GO and KEGG enrichment analyses, 93 Co-DEGs were associated with biological processes (BP), such as fibrinolysis, cell composition (CC), such as tertiary granules, and pathways, such as complement, and coagulation cascades. A differential gene expression analysis revealed significant differences between the Co-hub genes ANGPT2, MMP9, PLAU, and TIMP2. There was some accuracy in the diagnosis of NP based on the expression of ANGPT2 and MMP9. Analysis of differences in the immune cell components indicated an abundance of activated dendritic cells, effector memory CD8+ T cells, memory B cells, and regulatory T cells in both groups, which were statistically significant. In summary, we identified 6 Co-hub genes and 4 immune cell types related to NP and MDD. Further studies are needed to determine the role of these genes and immune cells as potential diagnostic markers or therapeutic targets in NP and MDD.

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Nonerythropoietic Erythropoietin Mimetic Peptide ARA290 Ameliorates Chronic Stress-Induced Depression-Like Behavior and Inflammation in Mice

Cited by 7 publications

References 55 publications

Erythropoietin‐derived peptide ARA290 mediates brain tissue protection through the β‐common receptor in mice with cerebral ischemic stroke

Erythropoietin‐derived peptide ARA290 mediates brain tissue protection through the β‐common receptor in mice with cerebral ischemic stroke

The Role of Macrophage Efferocytosis in the Pathogenesis of Apical Periodontitis

Bioinformatics and systems biology approach to identify the pathogenetic link of neurological pain and major depressive disorder

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