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Despite the investment in platinum drugs research, cisplatin, carboplatin and oxaliplatin are still the only Pt-based compounds used as first line treatments for several cancers, with a few other compounds being approved for administration in some Asian countries. However, due to the severe and worldwide impact of oncological diseases, there is an urge for improved chemotherapeutic approaches. Furthermore, the pharmaceutical application of platinum complexes is hindered by their inherent toxicity and acquired resistance. Nanodelivery systems rose as a key strategy to overcome these challenges, with recognized versatility and ability towards improving the safety, bioavailability and efficacy of the available drugs. Among the known nanocarriers, organic systems have been widely applied, taking advantage of their potential as drug vehicles. Researchers have mainly focused on the development of lipidic and polymeric carriers, including supramolecular structures, with an overall improvement of encapsulated platinum complexes. Herein, an overview of recent trends and strategies is presented, with the main focus on the encapsulation of platinum compounds into organic nanocarriers, showcasing the evolution in the design and development of these promising systems. This comprehensive review highlights formulation methods as well as characterization procedures, providing insights that may be helpful for the development of novel platinum nanocarriers aiming at future pharmaceutical applications.

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Woody invasive alien species can have profound impacts on ecosystem processes and functions, including fire regulation, which can significantly affect landscape resilience. Acacia dealbata, a widespread invasive alien plant in the Iberian Peninsula, holds well-known fire-adaptation traits (e.g., massive soil seed banks and heat-stimulated seed germination). In this study, we assess to what extent fire suppression and land-use strategies could affect the potential distribution of A. dealbata in a fire-prone transboundary protected mountain area of Portugal and Spain, using Habitat Suitability Models. Specifically, we predicted changes in habitat suitability for A. dealbata between years 2010 and 2050. We explored the potential impacts of two land-use strategies ('Business-as-usual' or 'High Nature Value farmlands') combined with three levels of fire suppression effectiveness using the biomod2 package in R. We also considered the potential effects of two climate change scenarios (RCP4.5 and RCP8.5). Our modeling approach demonstrated a strong capacity to predict habitat suitability using either climate or land-cover information alone (AUC climate = 0.947; AUC LC = 0.957). According to climate-based models, A. dealbata thrives under conditions characterized by higher precipitation seasonality, higher precipitation in the warmest month, and higher minimum temperature in the coldest month. Regarding land cover, A. dealbata thrives mainly in landscapes dominated by urban areas and evergreen forest plantations. Our models forecasted that habitat suitability by 2050 could either increase or decrease depending on the specific combinations of fire suppression, land-use, and climate scenarios. Thus, a combination of business-as-usual and fire-exclusion strategies would enhance habitat suitability for the species. Conversely, management promoting High Nature Value farmlands would decrease the available suitable habitat, particularly under low fire suppression efforts. These findings suggest that promoting sustainable farming activities could impede the spread of A. dealbata by reducing habitat availability, while strategies aiming at fire-exclusion could facilitate its expansion, likely by enabling establishment and large seed production. This study highlights the complex interplay between fire-prone invasive species, fire and land-use strategies, and climate change; and thus the need to consider the interactions between land-use and fire management to promote invasive species control and landscape resilience.

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[This corrects the article DOI: 10.3389/fpls.2023.974020.].

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Bioactive phytoconstituents have been increasingly investigated for their potential human health benefits. Corema album (L.) D. Don, an Ericaceae, reportedly has antioxidant, antimicrobial and anticancer properties. Aiming at enhancing its nutraceutical potential, we performed a spectrochemical analysis of hydroethanolic extracts from C. album leaves. We report on changes in the antioxidant activity of the extracts, as well as in the accumulation of key phytoconstituents (namely phenolic compounds), in female and male samples, throughout three harvesting seasons (February, July, and October). For each extract, the antioxidant activity was assessed by different spectrophotometric methods. Simultaneously, attenuated total reflectance Fourier transform mid-infrared spectroscopy (FTIR-ATR), and high-performance liquid chromatography - electrospray ionisation - quadrupole time-of-flight mass spectrometry (HPLC-ESI-Q-TOF-MS), were used to identify and monitor variations in the composition of phenolic compounds in the extracts. The main compounds identified were epicatechin, laricitrin-O-hexoside isomers, and myricetin-O-hexoside isomers. Significant differences were found in the composition and relative abundance of the compounds of interest, according to sex and season. Overall, a trend was observed whereby phenolic content and antioxidant activities were higher in males and increased between the earlier and the latest harvests. Based on these results, we may conclude that late summer or early autumn harvests are preferable when aiming at the highest yearly content of bioactive compounds. Additionally, it should be considered that extracts from male individuals typically display higher antioxidant activities. Ultimately, our understanding of C. album in the context of nutraceutical applications is benefited from the quantitative and qualitative portrait provided here, thus promoting its relevance as a source of bioactive compounds.

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Thymus carnosus Boiss. is a near-threatened species, and, as for many species, its potential for medicinal purposes may be lost if measures towards plant protection are not taken. A way of preserving these species is to increase knowledge about their medicinal properties and economic potential. Thus, with the objective of studying the potentiality of introducing T. carnosus as a crop, the stability of the phytochemical profile of T. carnosus was studied during a period of three years by comparing the phytochemical profile of extracts obtained from plants harvested in two different edaphoclimatic locations, as well as by comparing the respective bioactivities, namely, antioxidant, antidiabetic, antiaging, and neuroprotective activities. It was reported, for the first time, the effect of annual variation and geographic location in the phytochemical composition of aqueous decoction and hydroethanolic extracts of T. carnosus. In addition, the presence of two salvianolic acid B/E isomers in T. carnosus extracts is here described for the first time. Despite the variations in phytochemical composition, according to harvesting location or year, T. carnosus extracts maintain high antioxidant activity, assessed by their capacity to scavenge ABTS•+, •OH , NO•, O2•- radicals, as well as to prevent ß-carotene bleaching. All extracts presented significant potential to inhibit acetylcholinesterase (AChE), tyrosinase, and α-glucosidase, denoting neuroprotective, anti-aging, and anti-diabetic potential. In conclusion, the vegetative stage and location of harvest are key factors to obtain the maximum potential of this species, namely, a phytochemical profile with health benefit bioactivities.

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Introduction: Climate change has been driving warming trends and changes in precipitation patterns and regimes throughout Europe. Future projections indicate a continuation of these trends in the next decades. This situation is challenging the sustainability of viniculture and, thus, significant efforts towards adaptation should be then carried out by local winegrowers. Method: Ecological Niche Models were built, using the ensemble modelling approach, to estimate the bioclimatic suitability of four main wine-producing European countries, namely France, Italy, Portugal, and Spain, in the recent past (1989-2005), for the cultivation of twelve Portuguese grape varieties. The models were then used to project the bioclimatic suitability to two future periods (2021- 2050 and 2051-2080) to better understand the potential shifts related to climate change (modeled after Intergovernmental Panel on Climate Change's Representative Concentration Pathways 4.5 and 8.5 scenarios). The models were obtained with the modeling platform BIOMOD2, using four bioclimatic indices, namely the "Huglin Index", the "Cool Night index", the "Growing Season Precipitation index", and the "Temperature Range during Ripening index" as predictor variables, as well as the current locations of the chosen grape varieties in Portugal. Results: All models performed with high statistical accuracy (AUC > 0.9) and were able to discriminate several suitable bioclimatic areas for the different grape varieties, in and around where they are currently located but also in other parts of the study area. The distribution of the bioclimatic suitability changed, however, when looking at future projections. For both climatic scenarios, projected bioclimatic suitability suffered a considerable shift to the north of Spain and France. In some cases, bioclimatic suitability also moved towards areas of higher elevation. Portugal and Italy barely retained any of the initially projected varietal areas. These shifts were mainly due to the overall rise in thermal accumulation and lower accumulated precipitation in the southern regions projected for the future. Conclusion: Ensemble models of Ecological Niche Models were shown to be valid tools for winegrowers who want to adapt to a changing climate. The long-term sustainability of viniculture in southern Europe will most likely have to go through a process of mitigation of the effects of increasing temperatures and decreasing precipitation.

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Integrated management of biodiversity and ecosystem services (ES) in heterogeneous landscapes requires considering the potential trade-offs between conflicting objectives. The UNESCO's Biosphere Reserve zoning scheme is a suitable context to address these trade-offs by considering multiple management zones that aim to minimise conflicts between management objectives. Moreover, in Mediterranean ecosystems, management and planning also needs to consider drivers of landscape dynamics such as wildfires and traditional farming and forestry practices that have historically shaped landscapes and the biodiversity they host. In this study, we applied a conservation planning approach to prioritise the allocation of management zones under future landscape and climate scenarios. We tested different landscape management scenarios reflecting the outcomes of climate-smart and fire-smart policies. We projected the expected landscape dynamics and associated changes on the distribution of 207 vertebrate species, 4 ES and fire hazard under each scenario. We used Marxan with Zones to allocate three management zones, replicating the Biosphere Reserves zoning scheme ("Core area", "Buffer zone" and "Transition area") to address the various management objectives within the Biosphere Reserve. Our results show that to promote ES supply and biodiversity conservation, while also minimising fire hazard, the reserve will need to: i) Redefine its zoning, especially regarding Core Areas, which need a considerable expansion to help mitigate changes in biodiversity and accommodate ES supply under expected changes in climate and species distribution. ii) Revisit current management policies that will result in encroached landscapes prone to high intensity, uncontrollable wildfires with the potential to heavily damage ecosystems and compromise the supply of ES. Our results support that both climate- and fire-smart policies in the Meseta Ibérica can help develop multifunctional landscapes that help mitigate and adapt to climate change and ensure the best possible maintenance of biodiversity and ES supply under uncertain future climate conditions.

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In the original article [...].

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Exemestane has a limited aqueous solubility that leads to a very high variability in absorption when administrated orally. It is crucial to develop strategies to increase the solubility and bioavailability of this drug. To overcome these issues, the aim of the present work was the development of magnetic silica mesoporous nanoparticles (IOMSNs) to carry and release exemestane. Furthermore, these nanoparticles could be also used as Magnetic Resonance Imaging (MRI) contrast agents for treatment monitorization and tumor detection. MRI analysis showed that IOMSNs present a concentration dependent contrast effect, revealing their potential for MRI applications. Also, IOMSNs present a very good polydispersity (0.224) and nanometric range size (137.2 nm). It was confirmed that the nucleus is composed by magnetite and the silica coating presents tubes with MCM-41-like hexagonal structure. Both iron oxide nanoparticles and iron oxide mesoporous silica nanoparticles were not toxic in cell culture for 24 h. Exemestane was successful released for 72 h following a typical sustained release pattern, achieving a very high loading capacity (37.7%) and in vitro release of 98.8%. Taking into account the results it is possible to conclude that IOMSNs have a high potential to be used as theranostic for intravenous breast cancer treatment with exemestane.

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Climate change is expected to have strong social-ecological implications, with global but especially regional and local challenges. To assess the climatic vulnerability of a given territory, it is necessary to evaluate its exposure to climate change and its adaptive capacity. This study describes the development of an Action Plan for Adapting to Climate Change in the Tâmega and Sousa Region, a mountainous inter-municipal community in the North of Portugal. The goals were to identify the main impacts of climate change on water resources, agriculture, forests, biodiversity, and socioeconomic sectors, as well as to develop a plan, merging local and scientific knowledge through a transdisciplinary lens. This study describes an approach that combines modelling methods, applied in the different sectors, and participatory methods, based on the analysis of the perceptions of local actors. Results indicate that the target region will experience a generalized increase in temperature and a decrease in precipitation, which will negatively impact all studied social-ecological dimensions. Overall, local business and institutional agents perceive the primary and tourism sectors as the most vulnerable in the region. The described framework demonstrates the engagement process between relevant scientific experts and local practitioners, as well as how it is critical to understand the impacts of climate change and to support the co-design of an adaptation plan, which in turn can guide political and economic decision-making towards effective implementation of the plan. In addition, the difficulties and challenges encountered during this process are discussed to support future plans and strategies for local adaptation.

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The chestnut tree (Castanea spp.) is an important resource worldwide. It is cultivated due to the high value of its fruits and wood. The evolution between Castanea biodiversity and humans has resulted in the spread of chestnut genetic diversity. In 2019, the chestnut tree area worldwide was approximately 596 × 103 ha for fruit production (Southern Europe, Southwestern United States of America, and Asia). In Europe 311 × 103 t were produced. Five genetic poles can be identified: three in Greece, the northwest coast of the Iberian Peninsula, and the rest of the Mediterranean. Over the years, there have been some productivity changes, in part associated with climate change. Climate is considered one of the main drivers of biodiversity and ecosystem change. In the future, new challenges associated with climate change are expected, which could threaten this crop. It is essential to identify the impacts of climate change on chestnut trees, improving the current understanding of climate-tree interconnections. To deal with these projected changes adaptation strategies must be planned. This manuscript demonstrates the impacts of climate change on chestnut cultivation, reviewing the most recent studies on the subject. Furthermore, an analysis of possible adaptation strategies against the potentially negative impacts was studied.

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BACKGROUND: Climate change has been widely accepted as one of the major threats for global biodiversity and understanding its potential effects on species distribution is crucial to optimise conservation planning in future scenarios under global change. Integrating detailed climatic data across spatial and temporal scales into species distribution modelling can help to predict potential changes in biodiversity. Consequently, this type of data can be useful for developing efficient biodiversity management and conservation planning. The provision of such data becomes even more important in highly biodiverse regions, currently suffering from climatic and landscape changes. The Transboundary Biosphere Reserve of Meseta Ibérica (BRMI; Portugal-Spain) is one of the most relevant reserves for wildlife in Europe. This highly diverse region is of great ecological and socio-economical interest, suffering from synergistic processes of rural land abandonment and climatic instabilities that currently threaten local biodiversity.Aiming to optimise conservation planning in the Reserve, we provide a complete dataset of historical and future climate models (1 x 1 km) for the BRMI, used to build a series of distribution models for 207 vertebrate species. These models are projected for 2050 under two climate change scenarios. The climatic suitability of 52% and 57% of the species are predicted to decrease under the intermediate and extreme climatic scenarios, respectively. These models constitute framework data for improving local conservation planning in the Reserve, which should be further supported by implementing climate and land-use change factors to increase the accuracy of future predictions of species distributions in the study area. NEW INFORMATION: Herein, we provide a complete dataset of state-of-the-art historical and future climate model simulations, generated by global-regional climate model chains, with climatic variables resolved at a high spatial resolution (1 × 1 km) over the Transboundary Biosphere Reserve of Meseta Ibérica. Additionally, a complete series of distribution models for 207 species (168 birds, 24 reptiles and 15 amphibians) under future (2050) climate change scenarios is delivered, which constitute framework data for improving local conservation planning in the reserve.

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Air temperature plays a major role in the growth cycle of fruit trees. Chilling and forcing are two of the main mechanisms that drive temperate fruit development, namely dormancy and active plant development. Given the strong sensitivity of these crops to air temperature and the foreseeable warming under future climates, it becomes imperative to analyze climate change impacts for fruit trees. The fruit sector in Portugal has risen significantly over the last decades, gaining increasing importance both internally and through exports. The present research assesses the impacts of climate change on the chilling and forcing for economically relevant fruit trees in Portugal, namely apples, oranges, pears, and plums. To assess temperate fruit chilling and forcing conditions, the chilling portions (CP) and growing degree-hours (GDH) were computed over Portugal, for the recent-past (1989-2005) and future (2021-2080) periods, following two anthropogenic radiative forcing scenarios (RCP4.5 and RCP8.5). Future climate data were obtained from four regional-global climate model pairs to account for model uncertainties. Bias-correction methodologies were also applied. A spatial analysis over the main regions with PDO "Protected Denomination of Origin" or PDI "Protected Geographical Indication" of origin of each fruit tree was performed. Future projections show a clear decrease in chilling for all regions and fruit types in Portugal. Nonetheless, given the current chilling values in Portugal and the relative importance of chilling accumulation for each fruit type, these changes are more significant for certain varieties of apples than for other types of fruit. Regarding forcing, the future projections highlight an increase in its values throughout the different fruit tree regions in Portugal, which should lead to earlier phenological timings. These changes may bring limitations to some of the most important Portuguese temperate fruit regions. The planning of suitable adaptation measures against these threats is critical to control the risk of exposure to climate change, thus warranting the future sustainability of the Portuguese fruit sector, which is currently of foremost relevance to the national food security and economy.

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Luminescent organic-inorganic hybrids containing lanthanides (Ln3+) have been prominent for applications such as luminescent bio-probes in biological assays. In this sense, a luminescent hybrid based on dense silica (SiO2) nanospheres decorated with Eu3+ ß-diketonate complexes using dibenzoylmethane (Hdbm) as a luminescent antenna was developed by using a hierarchical organization in four steps: (i) anchoring of 3-aminopropyltriethoxysilane (APTES) organosilane on the SiO2 surface, (ii) formation of a carboxylic acid ligand, (iii) coordination of Eu3+ to the carboxylate groups and (iv) coordination of dbm- to Eu3+. The hybrid structure was elucidated through the correlation of thermogravimetry, silicon nuclear magnetic resonance and photoluminescence. Results indicate that the carboxylic acid-Eu3+-dbm hybrid was formed on the surface of the particles with no detectable changes on their size or shape after all the four steps (average size of 32 ± 7 nm). A surface charge of -27.8 mV was achieved for the hybrid, assuring a stable suspension in aqueous media. The Eu3+ complex provides intense red luminescence, characteristic of Eu3+5D0→7FJ electronic transitions, with an intrinsic emission quantum yield of 38%, even in an aqueous suspension. Therefore, the correlation of luminescence, structure, particle morphology and fluorescence microscopy images make the hybrid promising for application in bioimaging.

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The polyphenol compositions of Thymus × citriodorus and Thymus vulgaris extracts as obtained by exhaustive hydroethanolic (HE) extraction and aqueous decoction (AD) were compared. In addition, their compositions and bioactivities were compared to those of Thymus pulegioides and Thymus mastichina, grown under the same edaphoclimatic conditions, and Thymus carnosus. Rosmarinic acid was the most abundant polyphenol followed by luteolin-hexuronide, salvianolic acids I and K. Cluster analysis suggests a similarity of the polyphenol composition of T. citriodorus and T. vulgaris. A significant antioxidant activity was observed and correlated with their polyphenol levels. The same being observed for the higher anti-proliferative activity/cytotoxicity of HE extracts on Caco-2 and HepG2 cells as compared to AD extracts. Significant association between the total phenolic compounds with the anti-proliferative activity, for both cell lines, was observed. These results support the importance of salvianolic acids levels in Thymus extracts and their in vitro anti-proliferative/cytotoxic activities.

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Thymus zygis subsp. zygis is an endemic Portuguese plant belonging to the Thymus zygis species. Although T. zygis is commonly used as a condiment and as a medicinal herb, a detailed description of the polyphenol composition of hydroethanolic (HE) and aqueous decoction (AD) extracts is not available. In this work, we describe for the first time a detailed phenolic composition of Thymus zygis subsp. zygis HE and AD extracts, together with their antioxidant, anti-proliferative and anti-inflammatory activities. Unlike other Thymus species, T. zygis subsp. zygis extracts contain higher amounts of luteolin-(?)-O-hexoside. However, the major phenolic compound is rosmarinic acid, and high amounts of salvianolic acids K and I were also detected. T. zygis subsp. zygis extracts exhibited significant scavenging activity of ABTS+, hydroxyl (•OH), and nitric oxide (NO) radicals. Regarding the anti-proliferative/cytotoxic effect, tested against Caco-2 and HepG2 cells, the AD extract only slightly reduced cell viability at higher concentrations (IC50 > 600 µg/mL, 48 h exposure), denoting very low toxicity, while the HE extract showed a high anti-proliferative effect, especially at 48 h exposure (IC50 of 85.01 ± 15.10 µg/mL and 82.19 ± 2.46 µg/mL, for Caco-2 and HepG2, respectively). At non-cytotoxic concentrations, both extracts reduced the nitric oxide (NO) release by lipopolysaccharide (LPS)-stimulated RAW 264.7 cells (at 50 µg/mL, HE and AD extracts inhibited NO release in ~89% and 48%, respectively). In conclusion, the results highlight the non-toxic effect of aqueous extracts, both resembling the consumption of antioxidants in foodstuff or in functional food. Furthermore, the HE extract of T. zygis subsp. zygis is a source of promising molecules with antioxidant, anti-inflammatory and anticancer activities, highlighting its potential as a source of bioactive ingredients for nutraceutical and pharmaceutical industries.

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Out-of-field scattered and transmitted extrafocal radiation may induce secondary cancer in long-term survivors of external radiotherapy. Pediatric patients have higher life expectancy and tend to receive higher secondary radiation damage due to geometric and biological factors. The goal of this study is to characterize the location and the magnitude of extrafocal dose regions in the case of three-dimensional conformal radiotherapy and volumetric arc therapy, to apply this information to clinical treatment cases, and to provide mitigation strategies. Extrafocal dose has been investigated in a Varian TrueBeam linac equipped with a high-definition 120 multileaf collimator using different physical and virtual phantoms, dose calculation (including Monte Carlo techniques), and dose measurement methods. All Monte Carlo calculations showed excellent agreement with measurements. Treatment planning system calculations failed to provide reliable results out of the treatment field. Both Monte Carlo calculations and dose measurements showed regions with higher dose (extrafocal dose areas) when compared to the background. These areas start to be noticeable beyond 11 cm from the isocenter in the direction perpendicular to the multileaf collimator leaves' travel direction. Out-of-field extrafocal doses up to 160% of the mean dose transmitted through the closed multileaf collimator were registered. Two overlapping components were observed in the extrafocal distribution: the first is an almost elliptical blurred dose distribution, and the second is a well-defined rectangular dose distribution. Extra precautions should be taken into consideration when treating pediatric patients with a high-definition 120 multileaf collimator to avoid directing the extrafocal radiation into a radiosensitive organ during external beam therapy.

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In-phantom and in-vivo three dimensional conformal radiation therapy (3DCRT) and volumetric modulated arc therapy (VMAT) skin doses, measured with and without bolus in a female anthropomorphic phantom RANDO and in patients, were compared against treatment planning system calculated values. A thorough characterization of the metal oxide semiconductor field effect transistor measurement system was performed prior to the measurements in phantoms and patients. Patients with clinical indication for postoperative external radiotherapy were selected. Skin dose showed higher values with 3DCRT technique compared with VMAT. The increase in skin dose due to the use of bolus was quantified. It was observed that, in the case of VMAT, the bolus effect on the skin dose was considerable when compared with 3DCRT. From the point of view of treatment time, bolus cost, and positioning reproducibility, the use of bolus in these situations can be optimized.

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Thymus mastichina, also called mastic thyme or Spanish marjoram, is endemic to the Iberian Peninsula, where it is widely used in folk medicine especially for treating digestive and respiratory systems disorders, and as a condiment to season olives. This work describes for the first time the detailed phenolic composition of exhaustive hydroethanolic extracts and aqueous decoctions of Thymus mastichina. Unlike other species of the Thymus genera, Thymus mastichina extracts contain high amounts of salvianolic acid derivatives, with salvianolic acid A isomer being the main derivative. This isomer was identified in extracts from Thymus mastichina for the first time. Also, an undescribed salvianolic acid derivative in Thymus mastichina was identified and its structure was tentatively described. Extracts from Thymus mastichina showed significant scavenging activity of 2,2-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) radical cation, hydroxyl, and nitric oxide radicals. The anti-proliferative effect of both T. mastichina extracts were tested against Caco-2 and HepG2 cells; the hydroethanolic extract showed a high anti-proliferative activity against Caco-2 cells compared to HepG2 cells (at 24 h exposure, the concentration that inhibits 50% of proliferation, IC50, was 71.18 ± 1.05 µg/mL and 264.60 ± 11.78 µg/mL for Caco-2 and HepG2, respectively). Thus, these results make this species a promising candidate for further investigation of its anti-tumoral potential. Therefore, Thymus mastichina can be potentially used as a functional food (used as a decoction or herbal tea) or as a source of bioactive ingredients with antioxidant and anti-proliferative properties.

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The potential of Thymus pulegioides L. as an alternative and valuable source of functional ingredients has been assessed. For this purpose, the phenolic constituent profiles and the antioxidant, anti-proliferative, neuroprotective, anti-aging and anti-diabetic activities of both T. pulegioides aqueous decoctions (AD) and hydro-ethanolic extracts (HE) were studied and compared for the first time. Rosmarinic acid was the main phenolic compound, accounting for 35.2% or 47.8% of total identified phenols in AD or HE, respectively (58.5 and 151.9 mg g-1 extract). Furthermore, large amounts of luteolin-O-hexuronide (AD: 39.9 ± 2.5 mg g-1, HE: 60.8 ± 7.0 mg g-1), eriodictyol-O-hexuronide (AD: 19.9 ± 2.5 mg g-1, HE: 26.8 ± 7.0 mg g-1) and chrysoeriol hexoside (AD: 23.5 ± 0.7 mg g-1, HE: 16.0 ± 0.7 mg g-1) were found. Both extracts showed significant in vitro antioxidant activity and anti-proliferative activity against Caco-2 cells (IC50 82.25 µg mL-1 and 105.44 µg mL-1, AD and HE, respectively), and reduced hepatotoxicity (HepG2 cells). In general, both T. pulegioides extracts showed poor anti-diabetic activity, moderate anti-aging effects and high neuroprotective activity with both AD and HE extracts, at 0.5 mg mL-1, showing 80% inhibition of the acetylcholinesterase activity and 94% inhibition of the tyrosinase activity. The present study highlights the important potential of this herb as a functional food ingredient.

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