Resveratrol (RSV), a dietary polyphenol widely present in traditional medicinal plants and foods, exhibits antioxidant and anti-inflammatory properties that are relevant to ethnopharmacological strate Show more
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. Show less
Theogallin, a tea-derived polyphenol enriched in newly developed cultivars such as MK5601, has been shown to have cognitive benefits. However, its biological and mechanistic effects of theogallin rema Show more
Theogallin, a tea-derived polyphenol enriched in newly developed cultivars such as MK5601, has been shown to have cognitive benefits. However, its biological and mechanistic effects of theogallin remain unclear. Herein, we investigated the transcriptomic profiles of six mouse tissues after oral theogallin administration. Theogallin induced tissue-enriched transcriptional responses, particularly in the brain, where it activated memory-related and neuronal activity-related pathways through the upregulation of immediate-early genes (IEGs). These transcriptional changes closely resembled brain-derived neurotrophic factor (BDNF)-induced neuronal activation and contrasted with gene expression patterns associated with Alzheimer's disease. In aged mice, theogallin improved recognition memory and increased the expression of IEGs-associated proteins, while reducing neurodegeneration-linked markers. Theogallin also enhanced neuronal gene expression in SH-SY5Y cells, supporting a direct neuromodulatory role and further promoting neurite outgrowth. Therefore, theogallin is a functional enhancer of neuronal activation with potential therapeutic relevance for age-related cognitive decline and neurodegenerative disorders. Show less