Callistephin enhances the protective effects of isoflurane on microglial injury through downregulation of inflammation and apoptosis

Zhao,Lili; Chen,Shibiao; Liu,Tianyin; Wang,Xiuhong; Huang,Haijin; Liu,Weicheng

doi:10.3892/mmr.2019.10282

Callistephin enhances the protective effects of isoflurane on microglial injury through downregulation of inflammation and apoptosis

Authors:
- Lili Zhao
- Shibiao Chen
- Tianyin Liu
- Xiuhong Wang
- Haijin Huang
- Weicheng Liu
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Affiliations: Department of Anesthesiology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China
Published online on: May 22, 2019 https://doi.org/10.3892/mmr.2019.10282
Pages: 802-812

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Abstract

Microglia are the major immune cells in the central nervous system. Microglial activation can be beneficial or detrimental depending on the stimuli and the physiopathological environment. Microglial activation is involved in a variety of neurodegenerative disorders. Different anesthetic agents have exhibited diverse effects on microglial activation and the engulfment process. The anthocyanin callistephin has been demonstrated to have antioxidant and anti‑inflammatory properties, and these were assessed in the present study, with a focus on its effect on microglial activation. Mouse microglial cells C8‑4B were treated with 100 ng/µl lipopolysaccharide (LPS) and 1 ng/µl interferon‑γ. Cells were subsequently treated with 2% isoflurane, 100 µM callistephin or both. LPS promoted apoptosis in C8‑B4 cells, and this was reduced following treatment with isoflurane and callistephin. LPS‑treated C8‑B4 cells also exhibited enhanced production of reactive oxygen species and nitric oxide, excessive engulfment and increased caspase 3/7 activity. These detrimental alterations were suppressed following co‑treatment with isoflurane and callistephin. LPS‑induced apoptosis was facilitated via the expression of B‑cell lymphoma‑2 like 1 and poly (ADP‑ribose) polymerase, which were subsequently restored following treatment with isoflurane and callistephin. Callistephin was demonstrated to be involved in the modulation of inducible nitric oxide synthase, cytochrome c oxidase subunit 2, tumor necrosis factor‑α and nuclear factor‑κ B. Callistephin enhanced the protective effects of isoflurane by modulating engulfment and apoptosis in C8‑B4 cells. The potential underlying mechanism was identified to be the suppression of p38 phosphorylation. The present study thus suggested that the negative effects on microglial activity induced by LPS were ameliorated following treatment with callistephin, which also enhanced the effects of isoflurane. Callistephin may therefore constitute a candidate drug agent that may target inflammatory and growth regulatory signaling pathways, thus ameliorating certain aspects of neurodegenerative diseases.

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