Plant extracts have recently received increased attention as alternative sources of antimicrobial agents in the fight against multidrug-resistant bacteria. Non-targeted metabolomics liquid chromatography-quadrupole time-of-flight tandem mass spectrometry, molecular networking, and chemometrics were used to evaluate the metabolic profiles of red and green leaves of two Brassica juncea (L.) varieties, var. integrifolia (IR and IG) and var. rugosa (RR and RG), as well as to establish a relationship between the elucidated chemical profiles and antivirulence activity. In total, 171 metabolites from different classes were annotated and principal component analysis revealed higher levels of phenolics and glucosinolates in var. integrifolia leaves and color discrimination, whereas fatty acids were enriched in var. rugosa, particularly trihydroxy octadecadienoic acid. All extracts demonstrated significant antibacterial activity against Staphylococcus aureus and Enterococcus faecalis, presenting the IR leaves the highest antihemolytic activity against S. aureus (99 % inhibition), followed by RR (84 %), IG (82 %), and RG (37 %) leaves. Antivirulence of IR leaves was further validated by reduction in alpha-hemolysin gene transcription (∼4-fold). Using various multivariate data analyses, compounds positively correlated to bioactivity, primarily phenolic compounds, glucosinolates, and isothiocyanates, were also identified.

This study comprehensively characterized the metabolite profiles of six lettuce varieties and established the correlation between the elucidated profiles and their antivirulence effects. A total of 195 metabolites were annotated using LC-QTOF-MS/MS metabolomics assisted by molecular networking and integrated with chemometrics. Red varieties (red longifolia and lolla rosa) demonstrated higher chlorogenic and chicoric acids suggesting their antioxidant properties. In parallel, amino acids and disaccharides were enriched in romaine longifolia rationalizing its palatable taste and nutritional potential, while crispa, capitata, and lolla bionda presented a high β-carboline alkaloid content. The antibacterial and antihemolytic potential of all varieties against methicillin-sensitive and methicillin-resistant Staphylococcus aureus was assessed and validated by prominent downregulation of α-hemolysin transcriptional levels in both strains. Moreover, correlation analysis revealed sesquiterpenes, β-carboline alkaloids, amino acids, and oxy-fatty acids as the main bioactives. Results emphasize lettuce significance as a functional food and nutraceutical source, and highlight varieties naturally rich in antibacterial agents to adapt breeding programs.

Lepidium meyenii or Maca is widely cultivated as a health care food supplement due to its nutritional and medicinal properties. Although there are a few in-depth studies evaluating Maca antihypertensive effects, the correlations between the chemical constituents and bioactivity of the plant have not been studied before. Thus, the roots were extracted using different solvents (aqueous, methanol, 50% methanol, and methylene chloride) and investigated for their antihypertensive and antioxidant activities through several in vitro assays. The methanolic extract exhibited the best renin and angiotensin converting enzyme (ACE) inhibitory activities with IC₅₀ values of 24.79 ± 1.3 ng/mL and 22.02 ± 1.1 ng/mL, respectively, along with the highest antioxidant activity. In total, 120 metabolites from different classes, e.g., alkylamides, alkaloids, glucosinolates, organic acids, and hydantoin derivatives, were identified in the methanolic extract using ultrahigh-performance liquid chromatography/high-resolution mass spectrometry (UPLC/HRMS). Molecular docking simulations were used to investigate the potential binding modes and the intermolecular interactions of the identified compounds with ACE and renin active sites. Glucotropaeolin, β-carboline alkaloids, succinic acid, and 2,4-dihydroxy-3,5-cyclopentyl dienoic acid showed the highest affinity to target the ACE with high docking scores (S ranging from -35.32 to -22.51 kcal mol^-1) compared to lisinopril (S = -36.64 kcal mol^-1). Interestingly, macamides displayed the greatest binding affinity to the active site of renin with docking scores (S ranging from -22.47 to -28.25 kcal mol^-1). Further, β-carbolines achieved docking scores comparable to that of the native ligand (S ranging from -13.50 to -20.06 kcal mol^-1). Molecular dynamics simulations and MMPBSA were also carried out and confirmed the docking results. Additionally, the computational ADMET study predicted that the compounds attaining promising docking results had proper pharmacokinetics, drug-likeness characteristics, and safe toxicological profiles. Ultimately, our findings revealed that Maca roots could be considered a promising candidate as an antihypertensive drug.

Annona glabra L. (AngTE) and Annona squamosa L. (AnsTE) fruits have been widely used in cancer treatment. Accordingly, their extracts were used to synthesize silver nanoparticles via a biogenic route (Ang-AgNPs) and (Ans-AgNPs), respectively. Chemical profiling was established using UPLC-QTOF-MS/MS. All species were tested for anticancer activity against human cervical cancer cells (HeLa), prostate adenocarcinoma metastatic (PC3), and ovary adenocarcinoma (SKOV3) using sulphorhodamine B assay. Apoptosis was determined using Annexin flow cytometry along with cell cycle analysis and supported by a molecular docking. The antibacterial and synergistic effect when combined with gentamicin were evaluated. A total of 114 compounds were tentatively identified, mainly acetogenins and ent-kaurane diterpenes. AnsTE and Ans-AgNPs had the most potent cytotoxicity on HeLa and SKOV3 cells, inducing a significant apoptotic effect against all tumor cells. The AnsTE and Ans-AgNPs significantly arrested PC3, SKOV3, and HeLa cells in the S phase. The nanoparticles demonstrated greater antibacterial and antifungal activities, as well as a synergistic effect with gentamicin against P. aeruginosa and E. coli. Finally, a molecular docking was attempted to investigate the binding mode of the identified compounds in Bcl-2 proteins’ receptor, implying that the fruits and their nanoparticles are excellent candidates for treating skin infections in patients with ovarian or prostatic cancer.

Even though legumes are valuable medicinal plants with edible seeds that are extensively consumed worldwide, there is little information available on the metabolic variations between different dietary beans and their influence as potential anti-cholinesterase agents. High-resolution liquid chromatography coupled with mass spectrometry in positive and negative ionization modes combined with multivariate analysis were used to explore differences in the metabolic profiles of five commonly edible seeds, fava bean, black-eyed pea, kidney bean, red lentil, and chickpea. A total of 139 metabolites from various classes were identified including saponins, alkaloids, phenolic acids, iridoids, and terpenes. Chickpea showed the highest antioxidant and anti-cholinesterase effects, followed by kidney beans. Supervised and unsupervised chemometric analysis determined that species could be distinguished by their different discriminatory metabolites. The major metabolic pathways in legumes were also studied. Glycerophospholipid metabolism was the most significantly enriched KEGG pathway. Pearson’s correlation analysis pinpointed 18 metabolites that were positively correlated with the anti-cholinesterase activity. Molecular docking of the biomarkers to the active sites of acetyl- and butyryl-cholinesterase enzymes revealed promising binding scores, validating the correlation results. The present study will add to the metabolomic analysis of legumes and their nutritional value and advocate their inclusion in anti-Alzheimer’s formulations.