The Untargeted Phytochemical Profile of Three Meliaceae Species Related to In Vitro Cytotoxicity and Anti-Virulence Activity against MRSA Isolates

Background: A high mortality rate is associated with about 80% of all infections worldwide, mainly due to antimicrobial resistance. Various antimicrobial and cytotoxic activities have been proposed for Meliaceae species. This study aimed to evaluate the in vitro anti-virulence and cytotoxic effect of the leaf extracts of Aphanamixis polystachya, Toona ciliata and Melia azedarach against five MRSA strains and on three cancer cell lines, followed by biological correlation to their encompassed phytoconstituents. Material and Methods: We explored three plants of this family against a panel of Methicillin-resistant Staphylococcus aureus (MRSA) strains and several cancer cell lines to select the most promising candidates for further in vivo and preclinical studies. The phytochemical composition was evaluated by UHPLC–QTOF–MS untargeted profiling. Cell viability was assessed by SRB assay. Minimum Inhibitory Concentration was carried out by using the agar micro-dilution technique. Inhibition of biofilm formation and preformed biofilm disruption were assessed spectrophotomertically, according to the Sultan and Nabil method (2019). Results: A total of 279 compounds were putatively annotated to include different phytochemical classes, such as flavonoids (108), limonoids/terpenoids (59), phenolic acids (49) and lower-molecular-weight phenolics (39). A. polystachya extract showed the most potent cytotoxic activity against Huh-7, DU-145 and MCF-7 cell lines (IC50 = 3, 3.5 and 13.4 µg mL−1, respectively), followed by M. azedarach, with no effect recorded for T. ciliata extract. Furthermore, both A. polystachya and M. azedarach extracts showed promising anti-virulence and antimicrobial activities, with A. polystachya being particularly active against MRSA. These two latter extracts could inhibit and disrupt the biofilm, formed by MRSA, at sub-lethal concentrations. Interestingly, the extracts inhibited hemolysin-α enzyme, thus protecting rabbit RBCs from lysis. A. polystachya extract reduced the pigmentation and catalase enzyme activity of tested pigmented strains better than M. azedarach at both tested sub-MICs. Consequently, susceptibility of the extract-treated cells to oxidant killing by 200 mM H2O2 increased, leading to faster killing of the cells within 120 min as compared to the extract-non-treated cells, likely due to the lower antioxidant-scavenging activity of cells exhibiting less staphyloxanthin production. Conclusion: These findings suggested that both A. polystachya and M. azedarach natural extracts are rich in bioactive compounds, mainly limonoids, phenolics and oxygenated triterpenoids, which can combat MRSA biofilm infections and could be considered as promising sources of therapeutic cytotoxic, antibiofilm and anti-virulence agents

Valorization potential of Egyptian mango kernel waste product as analyzed via GC/MS metabolites profiling from different cultivars and geographical origins

Abstract Increasing attention has been given to mango (Mangifera indica) fruits owing to their characteristic taste, and rich nutritional value. Mango kernels are typically discarded as a major waste product in mango industry, though of potential economic value. The present study aims to outline the first comparison of different mango kernel cvs. originated from different localities alongside Egypt, e.g., Sharqia, Suez, Ismailia, and Giza. Gas chromatography–mass spectroscopy (GC–MS) post silylation analysis revealed that sugars were the major class being detected at 3.5–290.9 µg/mg, with some kernels originating from Sharqia province being the richest amongst other cvs. In consistency with sugar results, sugar alcohols predominated in Sharqia cvs. at 1.3–38.1 µg/mg represented by ribitol, iditol, pinitol, and myo-inositol. No major variation was observed in the fatty acids profile either based on cv. type or localities, with butyl caprylate as a major component in most cvs. identified for the first time in mango. Regarding phenolics, Sedeeq cv. represented the highest level at 18.3 µg/mg and showing distinct variation among cvs. posing phenolics as better classification markers than sugars. Multivariate data analyses (MVA) confirmed that the premium cvs “Aweis and Fons” were less enriched in sugars, i.e., fructose, talose, and glucose compared to the other cvs. Moreover, MVA of Zabdeya cv. collected from three localities revealed clear segregation to be chemically distinct. Sharqia originated mango kernels were rich in sugars (e.g., glucose and fructose), whilst sarcosine esters predominated in other origins