Morinda Officinalis Oligosaccharides Alleviate Post-Stroke Depression-Like Behaviors Alongside Increased Gut Microbial Diversity and Butyrate Levels and Reduced Hippocampal Pla2g4a Expression.
4 affiliations
- 1Academy of Military Medical Sciences, Academy of Military Sciences, Beijing, China.
- 2Graduate Collaborative Training Base of Academy of Military Medical Sciences, Hengyang Medical School, University of South China, Hengyang, China.
- 3Chinese PLA Medical School, Beijing, China.
- 4Anhui Medical University, Hefei, China.
Abstract
Background and purpose
Post-stroke depression (PSD) represents a common and debilitating complication after cerebral ischemia, yet mechanism-based therapies remain an urgent unmet need. The microbiota-gut-brain axis has been implicated in PSD pathophysiology, but the precise molecular pathways are largely elusive. Morinda officinalis oligosaccharides (MOO), a clinically approved antidepressant in China, exhibit poor oral absorption, raising the possibility of a gut-dependent mechanism.Experimental approach
Male C57BL/6J mice were subjected to transient middle cerebral artery occlusion (MCAO) followed by 21 days of chronic restraint stress (CRS) to establish a PSD model. MOO (50 mg/kg/day) was administered via gavage from Day 7 to 27. Depression-like behaviors, 16S rRNA-based gut microbiota profiling, short-chain fatty acid (SCFA) quantification, intestinal and blood-brain barrier integrity assessments, and hippocampal proteomics were performed. The transferability of MOO-associated fecal effects was assessed using a donor-controlled fecal microbiota transplantation (FMT) design. The butyrate-Pla2g4a relationship was further examined by sodium butyrate supplementation and AAV-mediated hippocampal Pla2g4a overexpression.Key results
MOO administration altered gut microbial composition, increased the abundance of probiotics and decreased the abundance of harmful bacteria, and was accompanied by increased fecal butyrate levels. The donor-controlled FMT experiment provided preliminary evidence that fecally transferable factors from MOO-treated PSD donors may contribute to behavioral improvements in PSD recipients. MOO and sodium butyrate treatment were associated with improved indices of intestinal and blood-brain barrier integrity. Hippocampal proteomics identified Pla2g4a, a phospholipase linked to neuroinflammation, as a candidate molecule related to the observed effects. Both MOO and sodium butyrate treatment were associated with reduced hippocampal Pla2g4a expression, and Pla2g4a expression was inversely correlated with butyrate levels. Hippocampal Pla2g4a overexpression attenuated the behavioral improvements associated with sodium butyrate treatment, supporting the functional involvement of Pla2g4a in the response to sodium butyrate.Conclusions and implications
MOO treatment was associated with improved depression-like behaviors in PSD mice, accompanied by gut microbial alterations, increased fecal butyrate, improved barrier integrity, and reduced hippocampal Pla2g4a expression. FMT findings provided preliminary evidence that fecally transferable factors from MOO-treated donors may contribute to behavioral improvements, while Pla2g4a overexpression attenuated the behavioral effects of sodium butyrate. These findings highlight a potential association among MOO, gut-derived butyrate, barrier integrity, and hippocampal Pla2g4a in PSD.
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BibTeX
@article{ma2026morinda,
title = {{Morinda Officinalis Oligosaccharides Alleviate Post-Stroke Depression-Like Behaviors Alongside Increased Gut Microbial Diversity and Butyrate Levels and Reduced Hippocampal Pla2g4a Expression.}},
author = {Hui Ma and Yue Chen and Xinzhou Deng and Xuan Fang and Wenhui Xiao and Qian Long and Lu Du and Fuze Du and Haonan Chen and Yan Wang and Bo Gao and Xin Qiao},
journal = {CNS neuroscience \& therapeutics},
year = {2026},
month = oct,
doi = {10.1002/cns.71238},
url = {https://europepmc.org/article/MED/42958990},
note = {CC BY},
}
RIS
TY - JOUR
TI - Morinda Officinalis Oligosaccharides Alleviate Post-Stroke Depression-Like Behaviors Alongside Increased Gut Microbial Diversity and Butyrate Levels and Reduced Hippocampal Pla2g4a Expression.
AU - Hui Ma
AU - Yue Chen
AU - Xinzhou Deng
AU - Xuan Fang
AU - Wenhui Xiao
AU - Qian Long
AU - Lu Du
AU - Fuze Du
AU - Haonan Chen
AU - Yan Wang
AU - Bo Gao
AU - Xin Qiao
PY - 2026
DA - 2026/10/30
JO - CNS neuroscience & therapeutics
DO - 10.1002/cns.71238
UR - https://europepmc.org/article/MED/42958990
AB - Background and purpose Post-stroke depression (PSD) represents a common and debilitating complication after cerebral ischemia, yet mechanism-based therapies remain an urgent unmet need. The microbiota-gut-brain axis has been implicated in PSD pathophysiology, but the precise molecular pathways are largely elusive. Morinda officinalis oligosaccharides (MOO), a clinically approved antidepressant in China, exhibit poor oral absorption, raising the possibility of a gut-dependent mechanism.Experimental approach Male C57BL/6J mice were subjected to transient middle cerebral artery occlusion (MCAO) followed by 21 days of chronic restraint stress (CRS) to establish a PSD model. MOO (50 mg/kg/day) was administered via gavage from Day 7 to 27. Depression-like behaviors, 16S rRNA-based gut microbiota profiling, short-chain fatty acid (SCFA) quantification, intestinal and blood-brain barrier integrity assessments, and hippocampal proteomics were performed. The transferability of MOO-associated fecal effects was assessed using a donor-controlled fecal microbiota transplantation (FMT) design. The butyrate-Pla2g4a relationship was further examined by sodium butyrate supplementation and AAV-mediated hippocampal Pla2g4a overexpression.Key results MOO administration altered gut microbial composition, increased the abundance of probiotics and decreased the abundance of harmful bacteria, and was accompanied by increased fecal butyrate levels. The donor-controlled FMT experiment provided preliminary evidence that fecally transferable factors from MOO-treated PSD donors may contribute to behavioral improvements in PSD recipients. MOO and sodium butyrate treatment were associated with improved indices of intestinal and blood-brain barrier integrity. Hippocampal proteomics identified Pla2g4a, a phospholipase linked to neuroinflammation, as a candidate molecule related to the observed effects. Both MOO and sodium butyrate treatment were associated with reduced hippocampal Pla2g4a expression, and Pla2g4a expression was inversely correlated with butyrate levels. Hippocampal Pla2g4a overexpression attenuated the behavioral improvements associated with sodium butyrate treatment, supporting the functional involvement of Pla2g4a in the response to sodium butyrate.Conclusions and implications MOO treatment was associated with improved depression-like behaviors in PSD mice, accompanied by gut microbial alterations, increased fecal butyrate, improved barrier integrity, and reduced hippocampal Pla2g4a expression. FMT findings provided preliminary evidence that fecally transferable factors from MOO-treated donors may contribute to behavioral improvements, while Pla2g4a overexpression attenuated the behavioral effects of sodium butyrate. These findings highlight a potential association among MOO, gut-derived butyrate, barrier integrity, and hippocampal Pla2g4a in PSD.
SN - 1755-5930
SN - 1755-5949
ER -