Menopause is a natural phase in a woman’s life marked by the cessation of menstruation, typically accompanied by hormonal fluctuations that have significant impacts on physical and mental health. While much attention has been given to the physical symptoms of menopause, such as hot flashes and osteoporosis, the neurocognitive consequences of hormonal fluctuations during the menopausal transition and the subsequent sustained estrogen loss after menopause have received less focus. Estrogen receptors (ERs), specifically ERα and ERβ, play a critical role in maintaining brain health, influencing mood, memory, and cognition. This review explores the connection between estrogen receptor signaling and mental health during menopause, focusing on mood disorders such as depression and anxiety, as well as cognitive decline and dementia. We discuss the molecular mechanisms by which ERs modulate brain function, including their effects on neuroplasticity, neurotransmitter systems, and gene expression. The review also examines current clinical approaches to managing menopausal cognitive and mental health issues, including hormone replacement therapy and selective ER modulators, while emphasizing the need for further research into alternative therapies and individualized treatments. The importance of estrogen receptors in the menopausal brain and their potential as therapeutic targets is critically evaluated, aiming to shed light on this often-overlooked aspect of menopause and aging.

In our previous study, we demonstrated that a standardized ethanol extract of Perilla frutescens var. acuta (PE) alleviates memory deficits in an Alzheimer’s disease mouse model by inhibiting amyloid β (Aβ) aggregation and promoting its disaggregation. However, the extent to which PE exerts additional cognitive benefits independent of Aβ pathology remained unclear. Here, we aimed to evaluate the effects of PE on synaptic plasticity and learning and memory functions. Male ICR mice were used, and cognitive impairment was induced by scopolamine administration. PE was orally administered at doses determined from previous studies, and cognitive performance was assessed using the passive avoidance, Y-maze, and Morris water maze tests. In parallel, hippocampal slices were employed to examine the effects of PE on synaptic plasticity. PE (100 and 300 μg/mL) significantly enhanced long-term potentiation (LTP) in a concentration-dependent manner without altering basal synaptic transmission. This facilitation of LTP was blocked by scopolamine (1 μM), a muscarinic acetylcholine receptor (mAChR) antagonist, and IEM-1460 (50 μM), a calcium-permeable α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (CP-AMPAR) inhibitor, indicating the involvement of mAChR and CP-AMPAR pathways. In vivo, PE (100, 250, and 500 mg/kg) treatment improved memory performance across all behavioral tasks and upregulated hippocampal synaptic proteins including GluN2B, PSD-95, and CaMKII. Collectively, these results demonstrate that PE ameliorates scopolamine (1 mg/kg)-induced cognitive impairment by enhancing synaptic plasticity, likely through modulation of mAChR, CP-AMPAR, and NMDA receptor signaling. These findings highlight the therapeutic potential of PE for memory deficits associated with cholinergic dysfunction.

Background/Objectives: Perilla frutescens var. acuta Kudo, a member of the Lamiaceae family, has been previously reported to reduce neuroinflammation and potentially decrease Aβ plaque accumulation in 5XFAD mice. In this study, we aimed to evaluate the anti-neuroinflammatory potential of a standardized 60% ethanol extract of Perilla leaves (PE), optimized for commercial application. Methods: The inflammatory response was assessed in LPS-stimulated BV2 microglial cells, and the cognitive improvement was evaluated in an AD animal model induced by intracerebroventricular injection of Aβ. Results: Using LPS-stimulated BV2 microglial cells and an Aβ-injected ICR mouse model of Alzheimer’s disease, we found that PE significantly suppressed the LPS-induced production of nitric oxide and pro-inflammatory mediators, including IL-6, TNF-α, NF-κB, iNOS, and COX-2, along with inhibition of JNK and p38 MAPK activation. Furthermore, PE upregulated CREB and BDNF expression. In vivo, PE administration alleviated Aβ-induced cognitive deficits, which were associated with reduced expression of JNK, NF-κB, iNOS, and COX and increased CREB/BDNF signaling in the hippocampus. Behavioral assessments—including passive avoidance, Morris water maze, novel object recognition, and Y-maze tests—confirmed the improvement in cognitive function. Conclusions: Collectively, these findings demonstrate that PE exerts significant anti-neuroinflammatory and neuroprotective effects, supporting its potential as a functional ingredient for cognitive enhancement.

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies, driven by chemoresistance and metabolic reprogramming centered on glucose-6-phosphate dehydrogenase (G6PD)-dependent pentose phosphate pathway activity. Exogenously administered autocrine motility factor (AMF) suppresses G6PD at transcriptional and protein levels, elevating intracellular reactive oxygen species (ROS) to cytostatic thresholds. Glycyrrhetinic acid (GA), a bioactive triterpenoid from licorice root, amplifies oxidative stress through mitochondrial membrane disruption, while concurrently downregulating multidrug resistance-associated ABC transporters. Three PDAC cell lines were treated with AMF variants and GA. Cell viability was assessed by MTT assay and clonogenic survival assays. Mechanistic endpoints included DCFDA fluorescence, Western blotting, RT-qPCR, and doxorubicin/Hoechst 33342 fluorescence for drug retention analysis. Among eight distinct AMF variants, HG-AMF demonstrated the greatest cytotoxic potency both alone and in combination with GA. HG-AMF suppressed G6PD mRNA and protein expression, inducing sustained ROS accumulation confirmed by DCFDA fluorescence. Co-treatment with GA produced enhanced ROS generation, clonogenic suppression, decreased mitochondrial membrane potential, and impaired drug efflux. HG-AMF and GA converge on G6PD-dependent metabolism and chemoresistance pathways, providing a rational basis for their combined application in PDAC therapy.

Existing studies of diabetes management have largely relied on dichotomous controlled/uncontrolled outcomes, which obscure the clinical heterogeneity of th

The gut–skin axis represents a bidirectional communication network linking the gut microbiota, microbial metabolism, immune regulation, and skin physiology. Natural bioactives derived from dietary plants, mushrooms, fermented foods, marine resources, and functional ingredients may influence skin health through both direct nutritional effects and host–microbiome metabolic interactions. This review provides a microbiome-centered, systems-level perspective on the relationships among dietary bioactives, gut microbial biotransformation, microbiome-derived metabolites, and skin aging-associated physiology. Particular attention is given to polyphenols, polysaccharides, carotenoids, peptides, fatty acids, probiotics, postbiotics, and fermented bioactive compounds as modulators of microbial composition and metabolic activity. Microbial metabolites, including short-chain fatty acids (SCFAs), indole derivatives, urolithins, phenolic metabolites, bile acid derivatives, and lipid-associated metabolites, are discussed as potential mediators linking diet and microbial metabolism with skin physiology. Their relevance to oxidative stress, inflammation, mitochondrial function, epidermal barrier homeostasis, extracellular matrix remodeling, and cellular senescence is critically evaluated according to the available level of evidence. Human intervention studies provide preliminary clinical support for selected probiotic and oral nutricosmetic interventions; however, direct evidence establishing microbiome-mediated effects on skin outcomes remains limited. Interindividual differences in microbial metabolic capacity may further contribute to heterogeneous responses to dietary interventions. Overall, this evidence-centered appraisal reveals a substantial gap between mechanistic plausibility and demonstrated human causality, emphasizing the need for studies that directly test microbiome mediation using integrated microbiome, metabolite, and skin-specific outcome measurements.