Main achievements

1.     Equisetum ramosissimum extracts (ER_EtOH80 and ER_D) protect against palmitic acid (PA)-induced cellular dysfunction through multiple mechanisms. The decoction extract (ER_D) primarily enhances mitochondrial function by increasing fatty acid β-oxidation (FAO), stimulating mitochondrial biogenesis, and improving oxidative phosphorylation (OXPHOS). The ethanolic extract (ER_EtOH80) acts mainly through activation of Nrf2-mediated antioxidant defenses, increasing glutathione (GSH) levels and antioxidant enzyme activities. Both extracts prevent lysosomal loss and enhance autophagy through AMPK pathway modulation. Together, these mechanisms reduce lipid accumulation and maintain cellular homeostasis, suggesting therapeutic potential for metabolic dysfunction-associated steatotic liver disease (MASLD) (10.3390/ph18010039; 10.1016/j.fbio.2025.107483).

2.     The abietane diterpene 7α-acetoxy-6β-hydroxyroyleanone (Roy), isolated from the acetonic extract of Plectranthus hadiensis Schweinf. (a South African species) (10.3390/molecules27123813) demonstrated a more effective action than temozolomide (TMZ), the first line treatment to glioblastoma. Similarly, another abietane diterpene – Parvifloron D (Parv D) isolated by our team from the acetonic extract of Plectranthus ecklonii Benth., also showed a better effect than TMZ (10.3389/fphar.2022.1006832).

Roy treatment not only hindered genes associated with DNA repair but also triggered caspase mediated apoptosis. Additionally, Roy suppresses the expression of anti-apoptotic proteins, promoting cell death (10.1016/j.jep.2024.118689).

Recently using both 2D and 3D GB cell models, with U87 cells used as a standard GB cell model and to generate monocellular and multicellular spheroids (U87, HMC3, and/or HBMEC cells), Roy significantly reduced spheroid size and metabolic activity over time, with the most pronounced effects observed in multicellular spheroids. This compound also inhibited cell proliferation by preventing colony formation and downregulating CDK4 and VEGFA mRNA levels. Roy's bioactivity was enhanced in the presence of conditioned medium (secretome from GB and/or microglia cells), exerting a neuromodulatory effect by targeting IL6/JAK2/STAT3 pathway and by suppressing the secretion of cytokines involved in the chronic inflammatory state within the GB microenvironment. Importantly, Roy was also able to cross the blood-brain barrier. These findings, in line with our previous work, underscore the cytotoxic potential of this natural compound, suggesting Roy as a promising lead candidate for future GB treatment strategies (10.3389/fphar.2026.1728792).

3.      Skin ageing is primarily caused by UV radiation and intrinsic oxidative stress. UV, a major cause of cell DNA damage, also induces the activation of various matrix metalloproteinases (MMPs) that degrade several components of the extracellular matrix such as collagen, aggrecan, elastin, fibronectin, gelatin and laminin, leading to premature skin ageing. Therefore, it is worth developing natural products-based cosmetics, capable of enhancing skin photoprotection and reducing oxidative stress. From a survey performed by us (10.3390/ph16030347), nine selected species were studied deeply regarding chemical-skin interactions, with 3 becoming the most promising (10.3390/ph18121889; 10.3390/antiox15010149) and finally with Pistacia terebinthus L. being the selected to develop skin care formulations (in preparation).

4.     Cruciferous vegetables belong to the Brassicaceae family and are widely represented in the Mediterranean Diet (MD): broccoli, cress, cabbage, cauliflower, rocket, etc. These plants have glucosinolates, phytocompounds that when hydrolysed by myrosinase in the plant and/or by gut microbiota, originate biologically active compounds with anticancer properties, including isothiocyanates (ITCs) and indoles. However, the cooking process significantly affects the concentration of available glucosinolates due to their hydrophilic characteristics, decreasing these vegetables' potential benefits. Additionally, myrosinase is thermolabile and its denaturation inhibits the reaction that produces the bioactive products, so traditional long cooking with a high amount of water should be avoided, with consumption of raw vegetables preferred (10.3390/pharmaceutics14010190). We developed a protocol to optimize the hydrolyzation of glucosinolates by myrosinase in 3 Brassicaceae popular in the MD, promoting a much higher content in ITCs with antitumoral effect in colorectal cancer (in press).

5.     N, N-dimethyltryptamine (DMT), an indole alkaloid widely found in nature, known for its presence in Ayahuasca, has psychoactive properties mediated primarily via the serotonergic pathway and 5-HT2A serotonin receptor agonism. It is a psychedelic tryptamine associated with intense visual hallucinatory phenomena, perceptual changes and profound spiritual experiences. We found that when volunteers inhaled 50 to 70 mg of DMT via smooking Changa (the root bark of Mimosa tenuiflora (Willd.) Poir.) the population receptive field (pRF) size in primary visual cortex (V1) was significantly increased in peripheral bins of eccentricity in the active condition (inhaled DMT). This novel finding may explain perceptual visual distortions induced by psychedelics, such as field blurring and the enlargement of nearby visual space, particularly at the visual periphery (tunnel vision). Our findings are also consistent with the hypothesis that the activation of the 5-HT2A serotonin receptor plays a key role in the neurophysiology of the visual effects induced by psychedelics (10.1016/j.neuroimage.2024.120718).