Alzheimer's disease (AD) is a complex, multifactorial neurodegenerative disorder whose core pathological hallmarks include Aβ aggregation, tau hyperphosphorylation, chronic neuroinflammation, oxidative stress, mitochondrial dysfunction, and gut microbiota dysbiosis. Lignans, a class of naturally occurring polyphenolic dimers widely distributed in medicinal plants and diet, exhibit multi-target neuroprotective effects with low toxicity. This review provides a systematic synthesis of the anti-AD pharmacological mechanisms underlying nine structurally distinct lignan subtypes-dibenzocyclooctadiene, tetrahydrofuran, bisepoxy, benzofuran, and biphenyl types-emphasizing scaffold-dependent structure-activity relationships. Key mechanistic pathways encompass direct inhibition of Aβ aggregation and tau phosphorylation, activation of the Nrf2 antioxidant signaling axis and PI3K/Akt pro-survival pathways, suppression of NF-κB-mediated neuroinflammation, restoration of cholinergic function, protection of mitochondria via SIRT3, inhibition of ferroptosis through Gsk3β/Nrf2/GPX4 signaling, and modulation of the gut-brain axis via microbiota-mediated conversion to enterolactone. This review addresses key pharmacokinetic limitations such as low oral bioavailability, rapid metabolism, and limited brain exposure, alongside strategies including structural modification, brain-targeted delivery systems, and gut microbiota modulation. Despite promising preclinical evidence, clinical translation remains limited. Future research priorities should focus on direct target validation, network pharmacology, optimized formulations, and well-designed clinical trials to develop lignans into next-generation anti-aging and anti-AD therapeutics.
Skin aging is a multidimensional biological process driven by intrinsic chronological changes, exposomal stress, endocrine-metabolic shifts, extracellular matrix remodeling, inflammaging, oxidative injury, barrier impairment, and microbiome dysbiosis. This review integrates current evidence on the endocrine-microbiome-skin axis and evaluates microbiome-directed bioactive strategies for preserving cutaneous homeostasis during aging. Particular attention is given to probiotics, prebiotics, postbiotics, synbiotics, phytoestrogens, polyphenols, bioactive peptides, antioxidants, mitochondrial protectors, adaptogens, and metabolic modulators. Their mechanisms are discussed in relation to collagen homeostasis, mitochondrial function, lipid barrier integrity, immune regulation, microbial metabolite signaling, and systemic endocrine-metabolic status. The review also examines advanced delivery platforms, including liposomes, solid lipid nanoparticles, nanostructured lipid carriers, polymeric nanocarriers, nanoemulsions, encapsulated microbiome-active systems, and stimuli-responsive carriers, emphasizing their potential to improve compound stability, skin retention, controlled release, and target-site precision. Translational limitations are critically addressed, including strain and formulation specificity, insufficient long-term safety data, incomplete nanocarrier toxicology, regulatory ambiguity, and the need for personalization according to hormonal, metabolic, and microbiome profiles. Overall, microbiome-directed bioactive compounds combined with precision delivery systems represent a promising, but still evolving, strategy for delaying skin aging and restoring cutaneous homeostasis.
Ziziphi Spinosae Semen (ZSS) is a traditional East Asian sedative-hypnotic herb with over 2000 years of clinical application. Spinosin (SPI), a characteristic flavone-C-glycoside, is the official quality marker and principal bioactive constituent of ZSS. Despite extensive research on SPI in recent years, a timely, comprehensive review integrating its pharmacological mechanisms, pharmacokinetic barriers, and translational strategies remains absent. Herein, a systematic literature search was conducted up to 31 May 2026, and we synthesize all available evidence on SPI's chemical properties, natural sources, pharmacology, pharmacokinetics, toxicology, structural derivatives, and advanced drug delivery systems. Our analysis reveals that SPI exerts broad-spectrum pharmacological activities via multi-target modulation of serotonergic/GABAergic neurotransmission, the ERK/CREB/BDNF axis, and the Nrf2/HO-1 pathway. However, its clinical translation is severely hindered by extremely low oral bioavailability (<1%) and limited blood-brain barrier penetration due to poor aqueous solubility and P-glycoprotein-mediated efflux. Novel formulations have achieved up to 5-fold enhancement in oral bioavailability in preclinical models. While toxicological studies support a favorable safety profile, long-term toxicity and human pharmacokinetic data are lacking. This review critically discusses key translational bottlenecks and proposes evidence-based future directions to advance SPI as a natural neurotherapeutic agent.
Emerging contaminants (ECs) represent a growing environmental problem due to their presence in various environmental matrices. In Mexico, research on ECs remains limited. This scoping review, conducted in accordance with the PRISMA-ScR guidelines, analyzes their environmental fate during the period 2004-2025, considering their distribution in surface and groundwater, sediments, and influents and effluents from wastewater treatment plants (WWTPs). The reviewed studies demonstrate the presence of pharmaceutically active compounds (PhACs), endocrine-disrupting compounds (EDCs), personal care products, phthalates, bisphenols, pesticides, illicit drugs, xanthines, perfluoroalkyl and polyfluoroalkyl substances (PFAS), metabolites, and industrial compounds. The Apatlaco, Cuautla, and Santa Catarina rivers exhibit the greatest diversity of ECs, while groundwater shows evidence of infiltration of PhACs, phthalates, bisphenols, and triclosan, associated with urban, industrial, and tourist discharges. In sediments, PhACs and EDCs accumulate at concentrations in the ng/g range, while phthalates reach concentrations of thousands of ng/g, indicating their affinity for the solid phase. At Mexican wastewater treatment plants, conventional treatment methods do not completely remove ECs, allowing residual amounts to be discharged into receiving bodies of water. Overall, national monitoring should be expanded to include metabolites, transformation products, and advanced treatment assessment.
