IGF-1 receptor is involved in the regulatory effects of icariin and icaritin in astrocytes under basal conditions and after an inflammatory challenge
Autor: | Na Li, Mei Zhang, Wen-Di Zhang, Su Chen, Zhong-Rui Du, Wen-Fang Chen |
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Rok vydání: | 2021 |
Předmět: |
Lipopolysaccharides
0301 basic medicine medicine.drug_class Primary Cell Culture Pharmacology Neuroprotection Receptor IGF Type 1 Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Mesencephalon medicine Animals Humans Receptor Protein kinase B Cells Cultured Neuroinflammation Flavonoids Neurotoxicity Receptor antagonist medicine.disease Disease Models Animal 030104 developmental biology chemistry Astrocytes Neuroinflammatory Diseases Biological regulation Icariin 030217 neurology & neurosurgery Signal Transduction |
Zdroj: | European Journal of Pharmacology. 906:174269 |
ISSN: | 0014-2999 |
Popis: | Icariin and icaritin, the major active components of Epimedii Genus, are considered as promising drugs with anti-inflammatory, anti-aging and neuroprotective effects. Our previous studies have demonstrated that icariin and icaritin can protect against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)/1-methyl-4-phenylpyridinium (MPP+)-induced neurotoxicity on dopaminergic neurons via insulin-like growth factor-1 receptor (IGF-1 receptor) signaling. In the present study, we aimed to evaluate the role of IGF-1 receptor signaling in mediating the anti-inflammatory effects of icariin and icaritin against lipopolysaccharide (LPS)-induced neuroinflammation as well as their biological regulation effects in midbrain primary astrocytes. Our results showed that both icariin and icaritin significantly inhibited LPS-induced mRNA expressions of tumor necrosis factor (TNF-α) and interleukin-1β (IL-1β). Pre-treatment with IGF-1 receptor antagonist JB-1 could significantly block the anti-inflammatory effects of icariin and icaritin on LPS-induced up-regulations of TNF-α, IL-1β, cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). Under basal conditions of astrocytes, icariin and icaritin treatment alone increased the phosphorylation of ERK1/2 and AKT, which could be blocked by JB-1. Moreover, the mRNA expressions of glutamate transptor-1 (GLT-1) and glutamate-aspartate transporter (GLAST) could be up-regulated by icariin and icaritin in a time-dependent manner via IGF-1 receptor. Taken together, our results suggest for the first time that both icariin and icaritin exert regulatory effects in astrocytes under basal conditions and after an inflammatory challenge via IGF-1 receptor signaling pathway. |
Databáze: | OpenAIRE |
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