(-)-Syringaresinol suppressed LPS-induced microglia activation via downregulation of NF-κB p65 signaling and interaction with ERβ

  • Int Immunopharmacol. 2021 Oct:99:107986. doi: 10.1016/j.intimp.2021.107986.
Lanqiu Zhang  1 ,  Xiaolin Jiang  2 ,  Jinlu Zhang  2 ,  Hejun Gao  3 ,  Lei Yang  2 ,  Dihua Li  2 ,  Qi Zhang  2 ,  Botao Wang  3 ,  Lihua Cui  2 ,  Ximo Wang  4
Affiliations
  • 1. Tianjin Key Laboratory of Acute Abdomen Disease Associated Organ Injury and ITCWM Repair, Institute of Acute Abdominal Diseases, Tianjin Nankai Hospital, Tianjin 300100, China. Electronic address: [email protected].
  • 2. Tianjin Key Laboratory of Acute Abdomen Disease Associated Organ Injury and ITCWM Repair, Institute of Acute Abdominal Diseases, Tianjin Nankai Hospital, Tianjin 300100, China.
  • 3. Graduate School, Tianjin Medical University, Tianjin 300070, China.
  • 4. Tianjin Key Laboratory of Acute Abdomen Disease Associated Organ Injury and ITCWM Repair, Institute of Acute Abdominal Diseases, Tianjin Nankai Hospital, Tianjin 300100, China. Electronic address: [email protected].
PMID: 34303280 DOI: 10.1016/j.intimp.2021.107986
Abstract

Albiziae Cortex (AC) is a well-known traditional Chinese medicine with sedative-hypnotic effects and neuroprotective ability. However, the bioactive components of AC responsible for the neuro-protective actitivity remain unknown. Here, we investigated the anti-neuroinflammatory effects of (-)-syringaresinol (SYR) extracted from AC in microglia cells and wild-type mice. As a result, (-)-SYR significantly reduced lipopolysaccharide (LPS)-induced production of interleukin - 6 (IL-6), tumor necrosis factor α (TNF-α), interleukin -1 beta (IL-1β), cycloxygenase-2 (COX-2), and nitric oxide (NO) in BV2 microglia cells. (-)-SYR also significantly reduced M1 marker CD40 expression and increased M2 marker CD206 expression. Moreover, we found that (-)-SYR inhibited LPS-induced NF-κB activation by suppressing the translocation of NF-κB p65 into the nucleus in a concentration-dependent manner. Meanwhile, Estrogen receptor β (ERβ) was found to be implied in the anti-inflammatory activity of (-)-SYR in BV2 microglia. In vivo experiments revealed that administration of (-)-SYR in mice significantly reduced microglia/astrocytes activation and mRNA levels of proinflammatory mediators. Taken together, our data indicated that (-)-SYR exerted the anti-neuroinflammatory effects by inhibiting NF-κB activation and modulation of microglia polarization, and via interaction with ERβ. The anti-neuroinflammatory activity of (-)-SYR may provide a new therapeutic avenue for the treatment of brain diseases associated with inflammation.

Keywords
(−)-Syringaresinol; Anti-neuroinflammation; ERβ; GFAP; Iba-1; Microglia.
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