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Luteolin and Apigenin Attenuate LPS-Induced Astrocyte Activation and Cytokine Production by Targeting MAPK, STAT3, and NF-κB Signaling Pathways

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Abstract

Astrocytes release biologically active substances that cause inflammation in neurodegenerative diseases. The present study investigated the effects of two flavonoids (apigenin and luteolin) on the production of IL-31 and IL-33 in lipopolysaccharide (LPS)-activated astrocytes. Cell viability was investigated using EZ-Cytox assay, mRNA expressions of IL-31 and IL-33 were analyzed by RT-PCR, protein expressions were analyzed by western blot, and cytokine secretion was analyzed by ELISA. Apigenin and luteolin prevented astrocyte activation and inhibited mRNA and protein expression and secretion of IL-31 and IL-33 in the LPS-treated astrocytes. Apigenin’s suppression of ERK, NF-κB, and STAT3 activations was responsible for the inhibition of IL-31 and IL-33, while luteolin’s suppression of JNK, p38, ERK, NF-κB, and STAT3 activations was responsible for the inhibition of IL-31 in the astrocytes. Also, luteolin’s suppression of ERK, NF-κB, and STAT3 activations inhibited IL-33 production in the activated astrocytes. In addition, apigenin and luteolin also prevented the translocation of activated STAT3 and NF-κB to the nucleus of the activated astrocytes and subsequently affected their DNA binding activities. The results suggest that apigenin and luteolin may have potentials as neuroprotective agents for the treatment of diseases involving astrocyte activation and detrimental production of IL-31 and IL-33.

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Data Availability Statement

The data used to support the findings of the study is included in the article, and the data are available from the corresponding author upon request.

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Funding

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (NRF-2019R1F1A1060332).

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Authors and Affiliations

  1. Department of Health Management, Jeonju University, 303 Cheonjam-ro, Wansan-gu, Jeonju-si, Jeollabuk-do, 55069, South Korea

    Denis Nchang Che, Byoung Ok Cho, Ji-su Kim, Jae Young Shin, Hyun Ju Kang & Seon Il Jang

  2. Department of Food Science and Technology, Jeonbuk National University, Jeonju-si, Jeollabuk-do, 54896, South Korea

    Denis Nchang Che

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Contributions

Seon Il Jang: conceptualization, methodology, resources, writing-review and editing, supervision. Byoung Ok Cho: methodology, writing-review and editing. Denis Nchang Che: methodology, investigation, and data analysis, writing-original draft. Ji-su Kim, Jae Young Shin, Hyun Ju Kang: validation and visualization.

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Correspondence to Seon Il Jang.

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Che, D.N., Cho, B.O., Kim, Js. et al. Luteolin and Apigenin Attenuate LPS-Induced Astrocyte Activation and Cytokine Production by Targeting MAPK, STAT3, and NF-κB Signaling Pathways. Inflammation 43, 1716–1728 (2020). https://doi.org/10.1007/s10753-020-01245-6

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