ArticleJournal of neuroinflammation2024
Secoisolariciresinol diglucoside attenuates neuroinflammation and cognitive impairment in female Alzheimer's disease mice via modulating gut microbiota metabolism and GPER/CREB/BDNF pathway.
Article in Journal of neuroinflammation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- Decoding the Gut-Fat-Heart Axis: From Molecular Communication Networks to Clinical Translation Strategies.International journal of molecular sciences · 2026Review
- Nutritional methionine restriction modulates gut microbiota and propionate/GPR41 signaling to mitigate diabetic kidney disease.NPJ science of food · 2026Article
- Comorbid Alzheimer's Disease and Type 2 Diabetes Microbiota Shape Age-Associated Gut-Brain Axis Profiles.Aging cell · 2026Article
- Chinese Herbal Medicine Targets Gut Microbiota to Combat Neurodegenerative Diseases: Potential Mechanisms and Clinical Implications.Journal of microbiology and biotechnology · 2026Review
- 3,4-Dihydroxybenzaldehyde Exerts Anti-Alzheimer's Effects by Inhibiting Aβ Protofibril Assembly and Activating Antioxidant Defense Mechanisms.International journal of molecular sciences · 2026Article
- Mechanism of Inosine fromFoods (Basel, Switzerland) · 2026Article
- Research advances on estrogen deficiency leading to depression.Translational neuroscience · 2026Review
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- Regulating the crosstalk betweenFrontiers in immunology · 2026Review
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- Pediococcus acidilactici attenuates chronic stress-induced depression via generating metabolite indole-3-lactic acid and downregulating neuroinflammation.Journal of neuroinflammation · 2025Article
- A Synbiotic ofNutrients · 2025Article
- Review
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- Associations of urinary enterolignans and risk of overall and cause-specific mortality with or without serum albumin adjustment: a prospective cohort study.Frontiers in nutrition · 2025Article
- Gut microbiota has the potential to improve health of menopausal women by regulating estrogen.Frontiers in endocrinology · 2025Review
- Plants, Pills, and the Brain: Exploring Phytochemicals and Neurological Medicines.International journal of plant, animal and environmental sciences · 2025Article
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Authors and funding
8 authors.
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Abstract
backgroundGender is a significant risk factor for late-onset Alzheimer's disease (AD), often attributed to the decline of estrogen. The plant estrogen secoisolariciresinol diglucoside (SDG) has demonstrated anti-inflammatory and neuroprotective effects. However, the protective effects and mechanisms of SDG in female AD remain unclear.
methodsTen-month-old female APPswe/PSEN1dE9 (APP/PS1) transgenic mice were treated with SDG to assess its potential ameliorative effects on cognitive impairments in a female AD model through a series of behavioral and biochemical experiments. Serum levels of gut microbial metabolites enterodiol (END) and enterolactone (ENL) were quantified using HPLC-MS. Correlation analysis and broad-spectrum antibiotic cocktail (ABx) treatment were employed to demonstrate the involvement of END and ENL in SDG's cognitive improvement effects in female APP/PS1 mice. Additionally, an acute neuroinflammation model was constructed in three-month-old C57BL/6J mice treated with lipopolysaccharide (LPS) and subjected to i.c.v. injection of G15, an inhibitor of G protein-coupled estrogen receptor (GPER), to investigate the mediating role of the estrogen receptor GPER in the cognitive benefits conferred by SDG.
resultsSDG administration resulted in significant improvements in spatial, recognition, and working memory in female APP/PS1 mice. Neuroprotective effects were observed, including enhanced expression of CREB/BDNF and PSD-95, reduced β-amyloid (Aβ) deposition, and decreased levels of TNF-α, IL-6, and IL-10. SDG also altered gut microbiota composition, increasing serum levels of END and ENL. Correlation analysis indicated significant associations between END, ENL, cognitive performance, hippocampal Aβ-related protein mRNA expression, and cortical neuroinflammatory cytokine levels. The removal of gut microbiota inhibited END and ENL production and eliminated the neuroprotective effects of SDG. Furthermore, GPER was found to mediate the inhibitory effects of SDG on neuroinflammatory responses.
conclusionThese findings suggest that SDG promotes the production of gut microbial metabolites END and ENL, which inhibit cerebral β-amyloid deposition, activate GPER to enhance CREB/BDNF signaling pathways, and suppress neuroinflammatory responses. Consequently, SDG exerts neuroprotective effects and ameliorates cognitive impairments associated with AD in female mice.
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