Isoastragaloside I inhibits NF-κB activation and inflammatory responses in BV-2 microglial cells stimulated with lipopolysaccharide

Liu,Hongshuai; Huang,Fei; Wu,Hui; Zhang,Beibei; Shi,Hailian; Wu,Xiaojun; Hu,Zhibi

doi:10.3892/ijmm.2017.3114

Isoastragaloside I inhibits NF-κB activation and inflammatory responses in BV-2 microglial cells stimulated with lipopolysaccharide

Authors:
- Hongshuai Liu
- Fei Huang
- Hui Wu
- Beibei Zhang
- Hailian Shi
- Xiaojun Wu
- Zhibi Hu
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Affiliations: Shanghai Key Laboratory of Compound Chinese Medicines, The Ministry of Education (MOE) Key Laboratory for Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, P.R. China
Published online on: August 30, 2017 https://doi.org/10.3892/ijmm.2017.3114
Pages: 1270-1276

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Abstract

The excessive activation of microglia in many neurodegenerative diseases is detrimental to neuronal survival. Isoastragaloside I (ISO I) is a natural saponin molecule found within the roots of Astragalus membranaceus, a famous traditional Chinese medicine. In the present study, the anti‑inflammatory effects and the mechanisms of action of ISO I on activated BV-2 cells stimulated with lipopolysaccharide (LPS) were investigated. ISO I dose‑dependently inhibited the excessive release of nitric oxide (NO) and tumor necrosis factor (TNF)-α in the LPS-stimulated BV-2 cells. Moreover, it decreased the production of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2), and mitigated the gene expression of interleukin (IL)-1β, TNF-α and iNOS induced by LPS. Further experiments revealed that ISO I decreased the phosphorylation levels of nuclear factor-κB (NF-κB), and suppressed its nuclear translocation and transactivation activity. In addition, it inhibited the activation of signaling pathway molecules, such as PI3K, Akt and mitogen-activated protein kinases (MAPKs). Taken together, our findings suggest that ISO I prevents LPS-induced microglial activation probably by inhibiting the activation of the NF-κB via PI3K/Akt and MAPK signaling pathways, indicating its therapeutic potential for neurological diseases relevant to neuroinflammation.

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