Berberine exerts neuroprotective activities against cerebral ischemia/reperfusion injury through up-regulating PPAR-γ to suppress NF-κB-mediated pyroptosis

  • Brain Res Bull. 2021 Dec;177:22-30. doi: 10.1016/j.brainresbull.2021.09.005.
Yingnan Zhao  1 ,  Zengkun Li  2 ,  Enrong Lu  1 ,  Qi Sheng  3 ,  Yu Zhao  4
Affiliations
  • 1. Department of Neurology (Six), The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, PR China.
  • 2. Department of Neurology, Harbin First Hospital, Harbin, Heilongjiang 150001, PR China.
  • 3. Department of Neurology, The Third People's Hospital of Shenzhen, Shenzhen, Guangdong 518000, PR China.
  • 4. Department of Neurology (Six), The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, PR China. Electronic address: [email protected].
PMID: 34517069 DOI: 10.1016/j.brainresbull.2021.09.005
Abstract

Objective: Berberine (BBR) is an anti-inflammatory alkaloid compound extracted from herbs. The purpose of this study is to probe the possible effect and the mechanism of BBR against cerebral ischemia/reperfusion (I/R) injury.

Methods: In vitro oxygen and glucose deprivation (OGD) model was established on neurons from rat hippocampus, which was then subjected to BBR, IVA337 (PPAR-γ agonist), or GW9662 (PPAR-γ antagonist) treatment, to identify their effects on neuronal Pyroptosis. MTT assay was utilized to determine cell survival rates, TUNEL staining for observation of β-tubulin and MAP2 expressions, qRT-PCR for detection of mRNA expression of PPAR-γ, Western blot for assessment of protein expressions of PPAR-γ and pyroptosis-related proteins (AIM2, NLPR3, ASC, cleaved-Caspase-1, GSDMD, and GSDMD-N), and ELISA for examination of IL-18 and IL-1β expressions.

Results: OGD modeling induced neuron Pyroptosis, as evidenced by increased expression levels of pyroptosis-related proteins as well as IL-1β and IL-18, and elevated cell Apoptosis rate. In addition, OGD exposure led to PPAR-γ up-regulation and NF-κB activation. Overexpression of PPAR-γ ameliorated cell Pyroptosis, while knockdown of PPAR-γ intensified neuron Pyroptosis that could be reversed by BBR. Furthermore, either BBR could block the activation of NF-κB signaling pathway through PPAR-γ.

Conclusion: BBR protects rats from cerebral I/R injury by up-regulating PPAR-γ to restrain NF-κB-mediated Pyroptosis.

Keywords
Berberine; Cerebral ischemia/reperfusion injury; NF-κB; PPAR-γ; Pyroptosis.
Products