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Извлечено: 997 / 997 (100.0%) Средняя confidence: 0.13
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Resveratrol Attenuates Neuroinflammation and Gut-Brain Axis Dysfunction Induced by Lead and Cadmium Co-Exposure by Modulating Gut Microbiota in Rats.

PMID: 41839449 · DOI: 10.1002/ptr.70301 · Phytotherapy research : PTR, 2026 · Huimao Liu, Dan Yang, Hanyan Cheng, Lijuan Cao, Xu Song, Xun Zhou, Yuanfeng Zou, Lixia Li, Renyong Jia, Dongmei Zhang, M
📄 Abstract

Resveratrol (RSV), a dietary polyphenol widely present in traditional medicinal plants and foods, exhibits antioxidant and anti-inflammatory properties that are relevant to ethnopharmacological strategies for protecting against environmental neurotoxicants. Given increasing real-world co-exposure to lead (Pb) and cadmium (Cd), elucidating RSV's capacity to preserve gut-brain axis (GBA) homeostasis has direct translational relevance for populations relying on phytochemical interventions. Sprague-Dawley rats were randomized into control, Pb-Cd model, and RSV treatment groups (10, 20, or 40 mg/kg). For 4 weeks, rats received Pb (300 mg/L) and Cd (50 mg/L) in drinking water with daily RSV. Cognitive function was assessed by Morris water maze; barrier integrity by Evans blue assay, histology, and Western blot for ZO-1/Occludin; synaptic ultrastructure by TEM; microbiota composition by 16S rRNA sequencing; and short-chain fatty acids (SCFAs) by GC-MS. Neurotransmitters (5-HT, GABA, SP, VIP) and cytokines (IL-6, IL-1β, TNF-α) were measured by ELISA. RSV improved spatial learning, reduced EB extravasation, preserved synaptic ultrastructure and proteins (BDNF, SYN, PSD-95), and restored intestinal architecture with increased ZO-1/Occludin. RSV attenuated cytokine release, normalized goblet cells, reversed dysbiosis by restoring Lactobacillaceae/Prevotellaceae, and increased acetate, propionate, and butyrate. It reinstated 5-HT and GABA while reducing SP and restoring VIP across serum, colon, and hippocampus. RSV attenuated Pb-Cd-associated neurotoxicity and was accompanied by improved intestinal and BBB-related readouts, partial normalization of gut microbiota features and SCFA levels, and preservation of synaptic and neurotransmitter-related markers, consistent with a link to gut-brain axis function. This study is among the first to test RSV in a Pb-Cd co-exposure model using a multi-dose regimen with integrated behavioral, barrier, microbial, and neurochemical endpoints.

Confidence: 0.13 · 6 полей извлечено
Идентификация (6 полей)
Target
Resveratrol
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Alt. target
RSV
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Protein family
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Functional class
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Subcellular loc.
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Isoforms (metab/obesity)
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Механизм действия (21 полей)
Mechanism
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Mutations (obesity/lean)
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Activity (obesity)
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Activity temporal
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Energy balance
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Appetite
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Fat metabolism
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Lipolysis
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Thermogenesis
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Muscle metabolism
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Inflammation
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Glucose metabolism
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AA metabolism
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Hormonal pathways
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Cell death
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Adipocyte fibrosis
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Upstream (biochem)
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Upstream (physiol)
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Downstream (biochem)
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Downstream (physiol)
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PTMs
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Экспрессия (8 полей)
Tissue expression
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In vitro
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In vivo
Sprague-Dawley rats randomized into control, Pb-Cd model, and RSV treatment groups (10, 20, or 40 mg/kg). Pb (300 mg/L) and Cd (50 mg/L) in drinking water for 4 weeks with daily RSV. Cognitive function assessed by Morris water maze; barrier integrity by Evans blue assay, histology, and Western blot for ZO-1/Occludin; synaptic ultrastructure by TEM; microbiota composition by 16S rRNA sequencing; SCFAs by GC-MS; neurotransmitters and cytokines by ELISA.
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In silico
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Genetic association
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Ex vivo
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Animal model
Sprague-Dawley rats
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Diet/model
Pb (300 mg/L) and Cd (50 mg/L) in drinking water for 4 weeks
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Клиника (11 полей)
Drug
Resveratrol
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Indication
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Patient subgroups
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Safety concerns
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Off-target
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Trial stage
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Pharma competitors
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MOA weight loss
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Endpoints
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Approved
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