The rapid spread of bacterial infection caused by Staphylococcus aureus has become a problem to public health despite the presence of past trials devoted to controlling the infection. Thus, the current study aimed to explore the chemical composition of the extract of endophytic fungus Aspergillus fumigatus, isolated from Albizia lucidior leaves, and investigate the antimicrobial activity of isolated metabolites and their probable mode of actions. The chemical investigation of the fungal extract via UPLC/MS/MS led to the identification of at least forty-two metabolites, as well as the isolation and complete characterization of eight reported metabolites. The antibacterial activities of isolated metabolites were assessed against S. aureus using agar disc diffusion and microplate dilution methods. Compounds ergosterol, helvolic acid and monomethyl sulochrin-4-sulphate showed minimal inhibitory concentration (MIC) values of 15.63, 1.95 and 3.90 µg/mL, respectively, compared to ciprofloxacin. We also report the inhibitory activity of the fungal extract on DNA gyrase and topoisomerase IV, which led us to perform molecular docking using the three most active compounds isolated from the extract against both enzymes. These active compounds had the required structural features for S. aureus DNA gyrase and topoisomerase IV inhibition, evidenced via molecular docking.

Alzheimer’s disease remains a global health challenge and an unmet need requiring innovative approaches to discover new drugs. The current study aimed to investigate the inhibitory activity of Albizia lucidior and Albizia procera leaves against acetylcholinesterase enzyme in vitro and explore their chemical compositions. Metabolic profiling of the bioactive plant, A. lucidior, via UHPLC/MS/MS-based Molecular Networking highlighted the richness of its ethanolic extract with budmunchiamine alkaloids, fourteen budmunchiamine alkaloids as well as four new putative ones were tentatively identified for the first time in A. lucidior. Pursuing these alkaloids in the fractions of A. lucidior extract via molecular networking revealed that alkaloids were mainly concentrated in the ethyl acetate fraction. In agreement, the alkaloid-rich fraction showed the most promising anticholinesterase activity (IC₅₀ 5.26 µg/mL) versus the ethanolic extract and ethyl acetate fraction of A. lucidior (IC₅₀ 24.89 and 6.90 µg/mL, respectively), compared to donepezil (IC₅₀ 3.90 µg/mL). Furthermore, deep in silico studies of tentatively identified alkaloids of A. lucidior were performed. Notably, normethyl budmunchiamine K revealed superior stability and receptor binding affinity compared to the two used references: donepezil and the co-crystallized inhibitor (MF2 700). This was concluded based on molecular docking, molecular dynamics simulations and molecular mechanics generalized born/solvent accessibility (MM–GBSA) calculations.

Roselle (Hibiscus sabdariffa L.) seeds, traditionally used in liver disorders, have recently attracted more attention as a new source of healthy edible oil with anti-inflammatory and antioxidant activities. However, its hepatoprotective effect has not been explored yet. In the current study, the hepatoprotective potential of roselle seed oil (RSO; 0.6, 4 and 8 ml/kg) and its nano-formulation (RSO-NE; 4 and 8 ml/kg), and their possible underlying mechanism were investigated in a paracetamol-induced hepatotoxicity rat model, compared to silymarin. RSO and RSO-NE protected the liver against paracetamol-intoxication and maintained the overall architecture of liver tissues in a dose dependent manner. Additionally, hepatic nuclear factor-erythroid 2-related factor2 (Nrf2) and glutathione (GSH) increased significantly in pre-treated groups, while malondialdehyde (MDA) decreased. Moreover, RSO and RSO-NE significantly inhibited paracetamol-induced mRNA expression of pro-inflammatory cytokines (TNF-α and IL-6). Chemical analysis of RSO showed fatty acids (mainly linoleic, oleic, palmitic and stearic acids), n-eicosane, β-sitosterol and tocopherols as the major constituents, which contributed synergistically to its protective effect. The efficacy of RSO-NE (8 ml/Kg) was superior to its corresponding unformulated oil (0.6 ml/kg), indicating its enhanced bioavailability. These findings encourage the use of RSO in development of health promoting products such as food supplements, functional food and nutraceuticals for the prevention of liver disease.

Background: Over the past centuries, Aloe species have been traditionally used in managements of infectious ailments. However, no scientific investigation has been conducted into their mechanistic actions behind their antimicrobial activities. The main purpose of this study is to investigate the anti-virulence activities of Aloe marlothii A. Berger (AM) and Aloe striata Haw (AS) leaves and roots against Pseudomonas aeruginosa based on biofilm, pyocyanin and motility assays. Besides, the metabolic profiling of their different organs was evaluated via HPLC–MS/MS analysis. A molecular docking study of marker compounds into a LasR target was conducted to gain an insight into the bioactive metabolites involved into mechanism of action. Results: A. marlothii roots (AMR) and A. striata leaves (ASL) displayed significant activity against P. aeruginosa at 0.5 MIC via decreasing the biofilm development, pyocyanin production, swarming and swimming motilities. HPLC–MS/MS analysis led to the identification of one hundred metabolites belonging to different chemical classes. Additionally, it revealed the richness of AMR and ASL with anthraquinones and anthrones. Molecular docking of tentatively identified anthraquinones and anthrones was performed, revealing that chrysophanol-8-O-glucoside and 6-malonylnataloin revealed superior binding affinities and stabilities within the pocket of LasR system, compared to TP-4. Conclusions: These findings give sound evidence for the use of AMR and ASL as effective anti-virulence agents against P. aeruginosa.

Hepatocellular carcinoma (HCC) is a global health challenge with a predicted high mortality rate in the future. Thus, discovering novel natural metabolites trimming the progression of HCC is an urgent necessity. In this study, we aimed to evaluate the effect of cytotoxic alkaloids isolated from endophytic fungus Aspergillus fumigatus, extracted from Albizia lucidior leaves (Fabaceae), against Huh7 cells and to further reveal their possible mechanisms on TP53 and c-Myc and their downstream tumor suppressor microRNAs (miRNAs). Pseurotin A and chaetominine revealed a concentration and time-dependent inhibition in cellular viability of Huh7 cells as well as significant repression in the proliferation and clonogenic capacities of Huh7 cells, compared to vehicle control. Pseurotin A exhibited more potent effects in halting Huh7 tumorigenic activity than chaetominine. Restoration of TP53, c-Myc, and their downstream tumor suppressor miRNAs; miR-30a, let-7i was achieved by pseurotin A only. Therefore, this study highlights a novel role of alkaloidal compounds from A. fumigatus in controlling the progression of HCC.