Candida albicans can cause various infections, especially in immunocompromised patients. Its ability to develop resistance to the current antifungal drugs as well as its multiple virulence factors have rendered the problem even more complicated. Thus, in the present investigation, we elucidated an in vitro and in vivo antifungal activity of Encephalartos laurentianus methanol extract (ELME) against C. albicans clinical isolates for the first time. A phytochemical identification of 64 compounds was conducted in ELME using LC-MS/MS. Interestingly, ELME exhibited antifungal activity with MIC values that ranged from 32–256 µg/mL. Furthermore, we investigated the antibiofilm activity of ELME against the biofilms formed by C. albicans isolates. ELME displayed antibiofilm activity using a crystal violet assay as it decreased the percentages of cells, moderately and strongly forming biofilms from 62.5% to 25%. Moreover, the antibiofilm impact of ELME was elucidated using SEM and fluorescent microscope. A significant reduction in the biofilm formation by C. albicans isolates was observed. In addition, we observed that ELME resulted in the downregulation of the biofilm-related tested genes (ALS1, BCR1, PLB2, and SAP5) in 37.5% of the isolates using qRT-PCR. Besides, the in vivo antifungal activity of ELME on the kidney tissues of rats infected with C. albicans was investigated using histological and immunohistochemical studies. ELME was found to protect against C. albicans induced renal damage, decrease desmin and inducible nitric oxide synthase, increase alkaline phosphatase, and increase infected rats’ survival rate. Additionally, the cytotoxicity of ELME was elucidated on Human Skin Fibroblast normal cells using MTT assay. ELME had an IC₅₀ of 31.26 µg/mL. Thus, we can conclude that ELME might be a promising future source for antifungal compounds.

LC-MS/MS analysis of Glechoma hederacea L. methanolic extract (GHME), revealed the identification of 25 metabolites. Ursolic acid (1), 2α-hydroxyursolic acid or corosolic acid (2), 2β-hydroxyursolic acid or epi-corosolic (3), luteolin 7-O-β-D-glucopyranoside (4) and rosmarinic acid (5) were isolated and identified using spectroscopy. Antibacterial activity of GHME against multi drug resistance Staphylococcus aureus clinical isolates was measured. Minimum inhibitory concentrations (MICs) were ranged from 62.5 to 500 µg/ml. In vivo wound healing potential of 2%, and 5% GHME prepared hydrogels were criticized on Staphylococcus aureus infected wound rat model. 5% GHME prepared hydrogel treated group showed significant (p < 0.05) shrinkage of their colony forming unit/ml (CFU/ml) values in comparison with standard Fucidin. Meanwhile, wound closure associated with full re-epithelization and hair follicles proliferation was noticed after ten days of treatment. Finally, among the GHME isolated compounds, luteolin 7-O-β-D-glucopyranoside (4) exhibited the highest molecular docking score (–9.6 kcal/mol) against matrix metalloproteinase-8 target (MMP-8). Graphical Abstract

A new triterpenoid named 3β,20α-dihydroxy-30-nor-olean-12-ene-23,28 dioic acid (4) along with 3β-hydroxy-23-aldehyde-lup-20(29)-ene-28-oic acid (1), 3β-hydroxy-23-aldehyde-30-nor-olean-12,20(29)-diene-28-oic acid (2), 3β-hydroxy-lup-20(29)-ene-23,28 dioic acid (3), 3β-hydroxy-lup-20(29)-ene-23,28 dioic acid-23-O-β-D-glucopyranosyl ester (5), 3-O-β-D-glucuronopyranosyl-lup-20(29)-ene-23,28 dioic acid-28-O-β-D-glucopyranosyl ester (6), 3-O-β-D-glucuronopyranosyl-lup-20(29)-ene-23-aldehyde-28-oic acid-28-O-β-D glucopyranosyl ester (7) were isolated for the first time from the aerial parts of Anabasis articulata (Forssk) Moq. Isolated pure compounds were structurally elucidated using spectral analysis. Cytotoxic, antimicrobial, antiulcer activities and antioxidant parameters were evaluated using the total methanol extract and its successive fractions. The methylene chloride fraction showed strong cytotoxic activity against HepG-2 (6.9 µg/ml) and HCT-116 (5.5 µg/ml) tumour cell lines in comparative with 5-fluorouracil (7.9 µg/ml). Treatment of indomethacin induced ulcerated rats with ethyl acetate fraction (400 mg/kg, p.o./day) achieved reduced Ulcer index (0.18), potent inhibition percentage of ulceration (84.86%) in comparison to ranitidine and high antioxidant effect. Compound(6) exhibited high docking score against gastric H⁺/K⁺ ATPase. Graphical Abstract

Anabasis articulata (Forssk) Moq. is a rich bioactive member of Family Amaranthaceae. GC/MS analysis of Anabasis articulata methyl esters fraction notified twenty known fatty acids, including n-hexadecanoic acid, octadecanoic acid and tetradecanoic acid as major constituents. Chromatography analysis of successive fractions revealed the isolation of β-sitosterol 1 from its unsaponifiable fraction, caffeine 2 form its methylene chloride fraction, and 4-acetoxy phenol 3 from the ethyl acetate one. Structural elucidation of these isolates was performed by IR, EI-MS, 1H NMR and 13C NMR techniques. Compounds 2 and 3 were isolated for the first time from Anabasis articulata (Forssk) Moq. Meanwhile, methanol extract of the tested plant showed weak total phenolic content. Environmental adaptation of pathogenic microbes through formation of resistible biofilm is constructing a dramatic health hazard, which demanded the exploration of more microbial resisting treatments. One successful strategy is the use of Phytoextracts as noncytotoxic, microbial biofilm inhibitors. Adopting the broth microdilution method, Anabasis articulata (Forssk) Moq. methanol extract (AAME) showed antimicrobial activity against Pseudomonas aeruginosa clinical isolates at range of 32 to 256 µg/mL minimum inhibitory concentrations (MIC). The inhibiting efficiency of AAME against Pseudomonas aeruginosa biofilm formation was concluded at a concentration of half its MIC value using the crystal violet assay (CVA). Our results illustrate the ability of this extract to cutback the percentage of strong, and moderate biofilm forming P. aeruginosa clinical isolates from 41.18 % to 17.65 % and candidate it as futural antibiofilm agent.

Background: This study is the first to elucidate the mechanistic actions of Atriplex portulacoides L. methanolic extract (APME) as a natural treatment of acetic acid-induced ulcerative colitis on rat model. Methods: Phytochemical metabolic profiling of APME was determined through the determination of total phenolic and flavonoid contents, alongside negative mode LC–ESI–MS/MS analysis. Furthermore, chromatographic and spectroscopic investigations were employed to fractionate and structurally characterize the metabolites present within APME fractions. The therapeutic potential of APME in UC was evaluated by integrating histological and immunohistochemical analyses. Quantification of oxidative stress, inflammation-related, and lncRNAs (FENDRR and Neat1) gene expression was established. Results: APME was evaluated for its total phenolic content and total flavonoid content. LC–ESI–MS/MS analysis in negative ionization mode identified 35 bioactive metabolites within APME. Stigmasterol (1) and 20-Hydroxyecdysone (2) were isolated by column chromatography from the n -hexane and ethyl acetate fractions, respectively, and characterized using spectroscopic analysis. APME dose-dependently and significantly ( p < 0.05) reduced the pro-inflammatory cytokine TNF-α, mitigated malondialdehyde levels, and restored total antioxidant capacity in colonic tissue compared to the untreated ulcerative group. APME`s treatments markedly upregulated the mRNA expression levels of Nrf2 and HO-1, while concurrently suppressing NF-κB mRNA expression. Also, it showed a regulatory effect on FENDRR and Neat1. Histological, immunohistochemical, and morphometric assessments further supported these findings, demonstrating substantial improvements in colonic architecture and cellular integrity. Discussion: Notably, APME represents a potential antioxidant and anti-inflammatory therapeutic candidate for UC. It modulates FENDRR and Neat1, revealing promising targets for IBD therapy.