Mauro Commisso

Phenylpropanoids are specialized metabolites involved in multiple aspects of plant physiology and contribute to fruit quality and human health benefits. In sweet cherry ( Prunus avium L.), metabolomic studies have largely focused on fruits, showing that cultivar identity contributes to phenylpropanoid pathway specialization. However, the contribution of genotype to phenylpropanoid organization in other organs, particularly leaves, remains poorly understood. Here, we applied an untargeted metabolomics approach to investigate genotype‐associated phenylpropanoid pathway specialization in sweet cherry leaves, using fruits as a reference organ. Leaves and fruits from seven sweet cherry cultivars (“Early Bigi”, “Burlat”, “Sandra”, “Grace Star”, “Romana”, “Durone Rosso”, and “Ferrovia”), representing early‐, mid‐ and late‐ripening genotypes, were sampled at full fruit maturity across multiple orchards and over two consecutive growing seasons. Distinct organ‐specific phenylpropanoid profiles were observed, with fruits characterized by the accumulation of anthocyanins, flavan‐3‐ols, and simple hydroxycinnamic acids, and leaves enriched in flavonols, hydroxycinnamic acids, and structurally diverse phenylpropanoid derivatives. Multivariate and univariate analyses identified cultivar identity as a major component of phenylpropanoid pathway specialization within each organ. Genotype‐associated differences involved multiple phenylpropanoid subclasses and remained detectable across growing seasons and orchard locations. Overall, these findings indicate differential channeling of the phenylpropanoid pathway between fruits and leaves and show that, within the range of environmental conditions covered by the present experimental design, genotype‐associated variation contributes to shaping phenylpropanoid composition in sweet cherry leaves, revealing a level of organization that had not been previously established in this organ.

Glioblastoma remains a highly aggressive and therapy-resistant brain tumor, with limited benefit from the current standard-of-care regimen combining surgery, radiotherapy, and temozolomide. Overcoming chemoresistance therefore represents a critical unmet clinical need. Here, we investigate the anticancer potential of Succisa pratensis and its ability to enhance TMZ efficacy in GBM models. Treatment with S. pratensis markedly reduced cell proliferation and migration while significantly increasing sensitivity to TMZ. Integrated multi-omics analyses revealed extensive metabolic rewiring, characterized by suppression of central carbon metabolism and activation of stress-adaptive pathways. Mechanistically, we identify the Pregnane X Receptor, a key regulator of drug metabolism and chemoresistance, as a central node affected by treatment. Although S. pratensis increased PXR expression, this was not accompanied by induction of canonical downstream targets, including MDR1 and ALDH1A1, indicating a functional impairment of PXR transcriptional activity. Consistently, pharmacological inhibition of PXR using the antagonist SPA70 further potentiated the cytotoxic effects of S. pratensis and TMZ. Docking analyses suggest that specific secondary metabolites, including apigenin-derived compounds, may interact with the PXR ligand-binding domain, providing a potential molecular basis for this effect. Collectively, our findings indicate that S. pratensis enhances TMZ efficacy by inducing metabolic vulnerability and functionally impairing PXR signaling. These results highlight the therapeutic potential of plant-derived metabolites as adjuvant strategies to overcome chemoresistance in glioblastoma.

Leaves of Actinidia chinensis Planch. var. deliciosa (A.Chev.) A.Chev. (A. deliciosa) represent agro-industrial byproducts with potential for valorization. The present study evaluated the metabolomics profiling, cytotoxicity, genotoxicity, and antigenotoxicity of the methanolic extract of A. deliciosa leaves. The metabolomics profiling was determined using an untargeted metabolomic approach employing UPLC-HRMS. Cytotoxicity, genotoxicity, and antigenotoxicity were assessed in Chinese hamster ovary K1 (CHO-K1) cells using the in vitro cytokinesis-block micronucleus (CBMN) assay. The metabolic profile of A. deliciosa leaf extracts revealed the presence of three major classes of secondary/specialized metabolites: proanthocyanidins, flavonols, and triterpenoid saponins. Medium-polar metabolites were monomeric fla-van-3-ols, such as (+)-catechin and (−)-epicatechin, oligomeric procyanidins and prodelphinidins, and flavonols. Certain glycosylated flavonols and their derivatives, such as myricetin, quercetin, and kaempferol. Low-polarity metabolites were characterized by low-polarity triterpenoids such as maslinic, corosolic, oleanolic, and ursolic acids. At concentrations of 37.5, 75, and 150 µg/mL, the extract did not significantly increase micronuclei frequency compared to untreated control cells, indicating an absence of genotoxic potential. Moreover, co-treatment of CHO-K1 cells with the extract and mitomycin C (MMC) at 0.025 µg/mL resulted in a significant reduction in micronuclei formation induced by MMC at concentrations of 75 and 150 µg/mL, suggesting antigenotoxic activity likely associated with the phytochemical constituents presented in the extract.

Anatomical and metabolomic variability in marine plants can provide valuable insights into species adaptive strategies and resilience to environmental changes. This study explores the anatomical characteristics and metabolomic profiles of Posidonia oceanica fruits, a key Mediterranean seagrass species, collected from three areas in Sardinia (Alghero, Oristano, and Olbia). Anatomical analyses of pericarps assessed cuticle thickness and intercellular spaces. Additionally, metabolomic analyses were performed using UPLC-HRMS on both the pericarps and the seeds. Significant differences in the percentage of intercellular spaces among pericarps from the different areas were found, with those from Alghero, exhibiting a higher percentage. Metabolomic analyses highlighted distinct profiles across areas, with Alghero pericarps showing greater metabolomics complexity, characterized by high levels of chicoric acid, hydroxycinnamate and hydroxybenzoate derivatives, while seeds exhibited an abundance of procyanidins, benzoic and caffeic acids and quercetins. Interestingly, seeds from Olbia presented a higher abundance of lipids. This study provides the first comprehensive metabolomic characterization of P. oceanica pericarps and seeds, highlighting significant variability that may influence seed dispersal, germination, and species adaptability. Our findings offer new perspectives for the conservation and management of this key species, which are particularly relevant in the context of global climate change.

Key message: ABC1K2 links stress response and seed development. The Activity of BC1 complex Kinases (ABC1K) family comprises atypical protein kinases with a conserved ABC1 domain and widespread distribution across life domains. In plants, ABC1Ks are predominantly localised in chloroplasts and mitochondria and have been implicated in energy metabolism, abiotic stress response, and developmental processes. Despite growing evidence of their biochemical activity, the functions of many ABC1Ks remain unclear. This study focuses on Arabidopsis thaliana ABC1K2, a plastidial clade member. ABC1K2 is principally localised in seeds; although it shows low expression in vegetative tissues, its transcription is induced by abscisic acid and stress. Functional analysis of abc1k2 mutants and overexpression lines reveals no major effects on plant development or fertility; however, mutant seeds exhibit increased size, mass, and altered pigmentation, along with reduced ABA levels and modified glucosinolate profiles. Transcriptomic data suggest that ABC1K2 integrates developmental signals with stress responses and secondary metabolism, particularly during seed development and germination. This work highlights a novel role for ABC1K2 in linking hormonal regulation and secondary metabolite biosynthesis, offering new insight into the functional diversification of the ABC1K protein family in plants.

Oxidative stress plays a critical role in the development of various chronic diseases, leading to major health problems worldwide. There has been increasing interest in using natural antioxidants as complementary agents for maintaining redox homeostasis and assuring a healthy lifestyle. This study aimed to systematically screen the antioxidant potential and cytotoxicity profiles of 19 plant-derived extracts using both a cell-free Fenton reaction-based assay and human monocytic THP-1 cells in vitro. The radical-scavenging capacity varied markedly among the extracts, with Acalypha virginica Linnaeus (ACALYPHA), Acorus calamus Linnaeus (ACORUS), Actinidia deliciosa (A.Chev.) C.F. Liang & A.R. Ferguson (ACTINIDIA), and Heuchera sanguinea Pursh (HEUCHERA) demonstrating strong activity in the chemical assay. In the cellular model, 15 extracts significantly reduced intracellular reactive oxygen species (ROS) levels without inducing cytotoxicity at effective concentrations. Notably, Acalypha virginica Linnaeus (ACALYPHA), Actinidia deliciosa (A.Chev.) C.F. Liang & A.R. Ferguson (ACTINIDIA), Dianthus superbus Linnaeus subsp. superbus (DIANTHUS), Succisa pratensis Moench (SUCCISA), and Typha laxmannii Lepech (TYPHA) exhibited consistent antioxidant efficacy across multiple doses. At higher concentrations, all extracts triggered apoptosis and/or necrosis, emphasizing the importance of defining safe ranges. These findings provide a comprehensive comparative analysis of Mediterranean plant-based natural antioxidants obtained by an in vitro approach. The selected plant extracts could be considered as promising candidates for the development of strategies targeting oxidative stress-related disorders. Further investigations considering the specific phytochemical composition of each extract and in vivo validation are needed to confirm their efficacy and safety.

Plant-based diets are associated with both physical health and psychological wellbeing. Recent evidence suggests that kiwifruit positively affects cognitive functions and mood, but the bioactive components responsible for this are unknown. In this work, we combined two predictive preclinical models of depression (TST and FST) with untargeted metabolomics to evaluate the antidepressant activity of green kiwifruit in mice and to identify the fruit bioactive phytochemicals responsible for this effect. Mice treated with green kiwifruit juice showed dose-dependent reductions in depressive behavior. Two kiwifruit-derived metabolites – quinic acid and caffeic acid sulfate (the latter formed in mice via metabolism of kiwifruit caffeic acid glucosides) – were detected in mouse serum and brain tissue, suggesting they may confer the observed effects. When administered as pure compounds, quinic acid closely replicated the antidepressant effect of kiwifruit juice, whereas caffeic acid glucoside had little impact. Other fruit metabolites may act synergistically with quinic acid to increase its bioavailability in serum and its absorption into the brain parenchyma. Our approach thus led to the discovery of quinic acid as the kiwifruit metabolite capable of rapidly reaching the mouse brain and exerting an antidepressant effect in synergy with other fruit metabolites.

Based on expression, functional, and metabolomic analyses in the seeds of the single-receptor mutants, each receptor has a specific function during seed development. Their redundant roles during this process are difficult to assess; moreover, the impact they have on plant development must also be taken into account. In this study, we investigated the role of cytokinin receptors in Arabidopsis thaliana seed development and their impact on the metabolomic profile. Our findings reveal distinct expression patterns among them in the seed: AHK2 expression is not detected in seed tissues, AHK3 is expressed in embryo, endosperm, and peripheral endosperm, while AHK4/CRE1 expression is restricted to a few embryo cells. These patterns are consistent with the observed phenotypes where ahk3 exhibits more severe seed phenotypes such as delayed embryo development and increased seed and endosperm size. Metabolomic analyses showed that the receptors impact the abundance of metabolites, with a remarkably high concentration of tannins in ahk2 with respect to wild type seeds, while ahk3 mutant seeds have a very low amount of tannins but elevated levels of other compounds such as sinapoylated glucosinolates (GSLs), important for plant defense. The metabolic profile performed further supports a link between cytokinin and the regulation of secondary metabolites such as flavonoids and glucosinolates. Our results suggest that each cytokinin receptor independently contributes to this regulation, reflected in the distinct metabolic profiles of each mutant.

Staphylea pinnata L., (S. pinnata), has long been recognized in Europe as both a wild food source and a traditional medicinal. This study aimed to characterize the metabolomic profile of the leaf extract of S. pinnata and assess its cytotoxic, genotoxic, and antigenotoxic effects in vitro for the first time. The methanolic extract of the leaves was analyzed using Ultra-Performance Liquid Chromatography–High-Resolution Mass Spectrometry (UPLC-HRMS). To evaluate its cytotoxic, genotoxic, and antigenotoxic properties, the cytokinesis block micronucleus assay was performed on Chinese hamster ovarian K1 cells. The analysis revealed a wide variety of metabolites in the extract, with B-type procyanidins and prodelphinidins being the most abundant. The genotoxicity of the extract varied depending on its concentration; at the lowest concentration (75 μg/mL), it showed no genotoxic effects and exhibited antigenotoxic properties by reducing the frequency of micronuclei induced by mitomycin C. However, at the highest concentration (300 μg/mL), the extract demonstrated genotoxic effects. In conclusion, the S. pinnata extract displayed both genotoxic and antigenotoxic properties, which may be attributed to its phytochemical composition. These findings highlight the complex nature of the plant’s bioactive compounds, suggesting potential therapeutic applications with careful consideration of dosage. Additional research is necessary to understand the mechanisms underlying these properties.