Research Paper Volume 15, Issue 7 pp 2705—2720
Berberine mitigates intracerebral hemorrhage-induced neuroinflammation in a gut microbiota-dependent manner in mice
- 1 Department of Nursing, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, Zhejiang, China
- 2 Department of Neurosurgery, Tiantai People’s Hospital of Zhejiang Province, Taizhou 317299, Zhejiang, China
- 3 Department of Neurosurgery, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, Zhejiang, China
Received: December 24, 2022 Accepted: March 24, 2023 Published: April 7, 2023
https://doi.org/10.18632/aging.204642How to Cite
Copyright: © 2023 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Background: Neuroinflammation is a frequent cause of brain damage after intracerebral hemorrhage (ICH). Gut microbiota are reported to regulate neuroinflammation. Berberine has been found to have anti-inflammatory actions, including in the central nervous system. However, it is not known whether berberine regulates neuroinflammation after ICH, nor is the relationship between the antineuroinflammatory actions of berberine and the gut microbiota after ICH understood.
Methods: ICH was induced in male mice by collagenase injection. Immunofluorescent staining and quantitative real-time polymerase chain reaction (qRT-PCR) were performed to detect microglia/macrophage phenotypes. Immunofluorescent staining, ELISA, and FITC-dextran were conducted to determine gut function. 16S rRNA sequencing of the fecal material was conducted to determine alterations in the gut microbiota. Antibiotic cocktail treatment and fecal microbiota transplantation (FMT) were used to deplete or restore the gut microbiota, respectively. Cylinder, forelimb placement and wire hanging tests were conducted to evaluate neurobehavioral function.
Results: Berberine significantly reduced neuroinflammation and alleviated neurological dysfunction by preventing microglial/macrophage proinflammatory polarization in ICH mice. Berberine also enhanced the function of the intestinal barrier, as shown by reductions in the levels of lipopolysaccharide-binding protein. Neuroinflammation in ICH mice was markedly reduced after transplantation of microbiota from berberine-treated mice, similar to treatment with oral berberine. In addition, a reduction in the microbiota reversed the neuroprotective effect of berberine.
Conclusions: Berberine is a potential treatment for ICH-induced neuroinflammation, and its effects are at least partially dependent on the gut microbiota.