Publicaciones

Polyphenols act in humans through authentic metabolites, including regio-isomeric glucuronides/sulphates, O-methylated forms, and microbiota products (urolithins, γ-valerolactones, equol), that reach targets by spatiotemporally gated exposure. Vectorial transport (MRP2/BCRP/P-gp), enterohepatic cycling, and β-glucuronidase hubs create early, surface-proximal microbursts of aglycone/catechol, whereas microbiota metabolites arrive systemically 6–24 h later. Signalling emerges from a continuum of weak noncovalent modulation, conditionally gated electrophile/redox relays (catechol → o-quinone, reversible Michael adduction plus signalling-range H2O2), and PTM cascades (phosphorylation → acylation → proteostasis) that reprogram NRF2/Keap1, NF-κB/IKK, AMPK/MAPK/PI3K-Akt, SIRT1/HDACs, PPARγ, AhR, and TFEB according to where and when metabolites appear. We provide methods and standards to dose isomer-resolved metabolites at physiological free concentrations (nM-low µM) in transport-competent systems, with PK-informed sampling across seconds–minutes, 15/60/240 min, and 6–24 h, and we outline a research agenda (reference panels, spatial exposure atlases, metabotype-stratified trials, safety windows). Framed this way, polyphenols shift from vague “antioxidants” to programmable dietary signals that enable precision nutrition targeting transcription-factor and proteostasis programmes in vivo.

Dehydrothyrsiferol (DT), a brominated oxasqualenoid from the red alga Laurencia viridis, represents a compelling example of this framework. This review establishes DT as a model Smart Secondary Metabolite based on the convergence of a unique molecular architecture of rigid stereogroups connected by flexible bonds; a high metabolic yield (0.42% w/w of crude extract); potent selective bioactivity against kinetoplastids and drug-resistant tumors; multi-target modulation of protein phosphatase 2A (PP2A) and cell-surface integrins; and distinctive chemotaxonomic relevance within Macaronesian communities. Its biosynthesis proceeds through stereocontrolled epoxide-opening cascades, generating an evolutionarily refined scaffold. Ecologically, DT operates as a multifunctional shield, providing antifouling protection and deterring herbivory. Pharmacologically, it acts as a selective signaling modulator, triggering integrin-mediated cell death (IMD) in resistant cancer cells and inducing mitochondrial collapse in protozoa. In vivo studies in murine models of cutaneous leishmaniasis have demonstrated an 87% reduction in lesion size, reinforcing its promise as a lead structure.

Silymarin (Silybum marianum (L.) Gaertn. extract) is a widely used botanical for liver disease, yet clinical results remain inconsistent. Most mechanistic work uses supraphysiological aglycones, whereas humans are exposed predominantly to phase II conjugates that are strongly protein-bound and routed by transporters toward bile and the intestinal mucosa. We reframe silymarin activity through a spatial pharmacology lens, proposing three post-intake windows: early (0–2 h) conjugate-dominant exposure with localised β-glucuronidase-mediated reactivation; intermediate (2–8 h) enterohepatic recirculation pulses; and late (8–48 h) microbial catabolite contributions. Each window engages distinct signalling modules—Keap1/NRF2, NF-κB, and AMPK-mTOR-TFEB—via transient redox events (quinone cycling, micro-H2O2 relays) and proteostatic remodelling (autophagy/mitophagy). We synthesise human pharmacokinetic and clinical evidence—with emphasis on MASLD and alcohol-associated liver disease—and show how formulation, meal timing, and microbiome metabotype determine which windows are engaged. Finally, we propose minimum reporting standards and falsifiable hypotheses to reduce between-study heterogeneity and enable precision use of silymarin.

Monascus food supplements are marketed because of the presence of hypocholesterolemic compounds and some species of the genus Monascus are characterized by their ability to biosynthesize industrially important azaphilone-type dyes. Although some colored compounds can photosensitize the singlet oxygen (1O2) generation, which is associated with chronodegenerative diseases, information on the photosensitizing capacity of Monascus dyes and Monascus based-products is lacking. Therefore, in this study, the photosensitizing capacity to generate 1O2 of Monascus purpureus extracts together with the main compound isolated, monascin, was evaluated through the photo-oxidation of ergosterol method (CFL-T4-GE 20W, λ > 380 nm, 19625 ± 129 lux, 2 h). In addition, the photosensitizing capacity of a Monascus food supplements was also evaluated. Subsequently, a thermodynamic theoretical analysis of the six most frequently reported azaphilones from M. purpureus was performed utilizing the time-dependent density functional theory (TD-DFT) to compare Gibbs free energies in relation to their potential as photosensitizers. Thus, the photo-oxidation of ergosterol using M. purpureus extracts, monascin and the Monascus food supplement extract as photosensitizers, combined with the computational study of the azaphilones from this fungal species, demonstrated that the metabolites of this species can transfer energy to molecular oxygen (3O2) through photosensitization processes to generate 1O2. Therefore, this study opens the door to further in vitro and in vivo research on 1O2 generation by Monascus pigments to assess the potential health risks associated with frequent use of Monascus food supplements and, if necessary, to introduce appropriate regulatory measures for the marketing of Monascus food supplements based on their ability to generate 1O2.

Natural products from bryophytes represent an underexplored source of structurally diverse bioactive compounds. In this study, extracts of Isotachis serrulata collected in southern Ecuador were evaluated for antiproliferative activity against five human tumor cell lines. Sequential extraction and chromatographic fractionation yielded six fractions, among which fraction IsF5 displayed the most notable activity, particularly against lung (SW1573) and breast (T-47D) cancer cell lines, with GI50 values within the moderate activity range according to National Cancer Institute criteria. Phytochemical investigation of IsF5 revealed the presence of two glycosylated aromatic constituents, tentatively assigned as tachioside and isotachioside, based on comparative 1H and 13C NMR spectroscopic analysis. These compounds were obtained as a mixture and were not evaluated individually due to limited material. Additionally, species distribution modeling using MaxEnt indicated that I. serrulata is primarily associated with humid montane and páramo ecosystems in the southern, central and northern Andes of Ecuador, where elevation and precipitation variables strongly influence its distribution. This study provides the first integrated assessment of the antiproliferative activity, chemical profiling, and ecological distribution of I. serrulata.

Chagas disease, caused by the protozoan Trypanosoma cruzi, remains a serious public health concern, particularly in Latin America, due to its high prevalence and the limited efficacy and safety of current treatments. To identify new potential therapeutic options, a library of 40 synthetic indole derivatives was screened for antiparasitic activity. The compounds were tested against both epimastigote and intracellular amastigote forms of T. cruzi using in vitro assays. While most of the molecules showed low or no activity, ten compounds exhibited promising effects with IC₅₀ values below 200 μM. The most active derivatives were further evaluated for cytotoxicity on mammalian cells. Among them, the compound I – 7b stood out with a selectivity index of 19.8 and was selected for further characterization. Subsequent assays revealed that this compound induced several cellular effects in the parasite, including ATP depletion, chromatin condensation, plasma membrane damage, reactive oxygen species (ROS) accumulation, and disruption of mitochondrial membrane potential (ΔΨm). These findings suggest that certain indole-based compounds may serve as promising scaffolds for the development of novel therapies against T. cruzi, contributing to the advancement of global health efforts targeting neglected tropical diseases.

Invasive alien species are one of the most severe threats to island biodiversity. An essential first step in addressing this issue is producing comprehensive inventories of alien species inhabiting them. However, cataloguing alien floras on remote islands is particularly challenging. Botanical surveys are often conducted only after substantial human-driven impacts on local ecosystems, including the introduction of invasive species, have already occurred. This raises the key question of how species’ native origin should be determined on islands with such a recent history of botanical documentation. Site-based methodologies offer a practical, replicable and context-sensitive approach to addressing these challenging knowledge gaps. Here, we present a comprehensive catalogue of the alien spermatophyte flora of Isla del Coco, an eastern Pacific island located approximately 500 km off the Central American mainland and facing the aforementioned challenges. Among the main contributions of this study, we apply an expert-based binary decision tree to classify the wild flora as native, wild alien, or cryptogenic, along with a separate inventory of cultivated species. Our classification system allowed us to identify 89 wild alien species (45.2% of the island’s total wild flora), 78 native species (39.6%), and 30 cryptogenic (15.2%). The naturalised-to-native ratio (0.5) suggests that the island remains highly susceptible to biological invasions. The profile of the alien flora closely resembles that of mainland Central America, with a predominance of unintentionally introduced species, underscoring the need for strict biosecurity measures at landing points. The methodology employed also indicates that site-based approaches may apply stricter criteria for defining native species than previous studies, thereby highlighting new research needs for Isla del Coco, such as clarifying the status of cryptogenic species and investigating the largely unexplored impacts of invasive alien plants.

Cellular redox biology is governed less by bulk oxidant load than by the coupled behaviour of ROS, RNS, and RSS within spatially restricted microdomains. Within these niches, redox information is written, edited, and erased through competing post-translational modifications, including sulphenylation (-SOH), S-nitrosylation (-SNO), and persulphidation (-SSH). Local proximity to sources such as mitochondria, NOX, and NOS platforms combines with buffering by SOD and peroxidases to shape which routes dominate. Editing by thioredoxin, glutaredoxin, and GSNOR, together with sulphane sulphur flux from trans-sulphuration enzymes and mitochondrial sulphide oxidation, sets the boundary between reversible redox eustress and pathological distress dominated by peroxynitrite chemistry and irreversible oxidation. Using a compartment-aware analytical template across cardiometabolic disease, neurodegeneration, cancer, chronic inflammation, ageing, and innate immunity, we identify recurring mechanistic patterns and explain why global biomarkers can mislead. We then propose context-matched biomarker panels and therapeutic levers, with antimicrobial peptides emerging as redox-modulated effectors of innate defence within this framework. Finally, we outline precision redox pharmacology that raises local distress thresholds without flattening physiological signalling, and we propose a trial-ready agenda centred on compartment-resolved pharmacodynamic anchors.

Acanthamoeba infections are hindered by limitations including prolonged treatment duration, cytotoxicity, limited efficacy against the resistant cystic stage, and a high rate of recurrence. Antimicrobial peptides (AMPs) demonstrate broad-spectrum antimicrobial activity, rapid mechanism of action, low potential for inducing resistance, and efficacy against both trophozoite and cyst forms, highlighting their potential as promising alternatives in the treatment of these infections. Herein, we report the amoebicidal activity of various peptides derived from cathelicidins and piscidins against Acanthamoeba castellanii Neff. Afterwards, the impact of the most effective peptide on the clinical features of a clinical strain of Acanthamoeba castellanii was evaluated using a fluorescence imaging system. Peptide OH_KR34 was the most active against A. castellanii Neff with an IC₅₀ values of 2.00 ± 0.58 µM. OH_KR34 was able to inhibit the clinical strain of A. castellanii (L10) with an IC50 of 5.75 ± 0.30 μM. We demonstrated that the peptide OH_KR34 (related to OH-CATH) induces cytoskeletal damage and trigger apoptosis-like process by disrupting cell membrane permeability, mitochondrial dysfunction and DNA fragmentation. This antimicrobial peptide could therefore offer a potential target to develop new anti-parasitic drugs.

Khirigsuurs are Late Bronze Age monuments found across Mongolia. Although mostly interpreted as mortuary structures, there is broad agreement that khirigsuurs also served as settings for communal rituals and seasonal gatherings. A key feature is the selective deposition of horse remains, mainly skulls, neck vertebrae, and hooves, while meaty axial and long bones are absent. This study investigates whether large-scale butchering and feasting took place at or near khirigsuurs through soil phosphate analysis and shovel testing at two sites in Züünkhangai, Mongolia. Results show no significant phosphate enrichment or bone concentrations, suggesting that intensive butchering did not occur at these sites. Archaeological, ethnographic, and historical sources suggest that butchering occurred off-site, with portions of the animals brought to khirigsuurs for ceremonial use. This practice, common in pastoralist societies, likely accounts for the absence of large bones at the monuments. Further research into off-site butchering and discard locations is needed to better understand the ritual practices and animal treatment associated with khirigsuurs.