Methotrexate (MTX) therapy encounters significant limitations due to the significant concern of drug-induced liver injury (DILI), which poses a significant challenge to its usage. To mitigate the deleterious effects of MTX on hepatic function, researchers have explored plant sources to discover potential hepatoprotective agents. This study investigated the hepatoprotective effects of the ethanolic extract derived from the aerial parts of Chamaecyparis lawsoniana (CLAE) against DILI, specifically focusing on MTX-induced hepatotoxicity. UPLC-ESI-MS/MS was used to identify 61 compounds in CLAE, with 31 potential bioactive compounds determined through pharmacokinetic analysis. Network pharmacology analysis revealed 195 potential DILI targets for the bioactive compounds, including TP53, IL6, TNF, HSP90AA1, EGFR, IL1B, BCL2, and CASP3 as top targets. In vivo experiments conducted on rats with acute MTX-hepatotoxicity revealed that administering CLAE orally at 200 and 400 mg/kg/day for ten days dose-dependently improved liver function, attenuated hepatic oxidative stress, inflammation, and apoptosis, and reversed the disarrayed hepatic histological features induced by MTX. In general, the findings of the present study provide evidence in favor of the hepatoprotective capabilities of CLAE in DILI, thereby justifying the need for additional preclinical and clinical investigations.

Prior studies have extensively investigated the essential oil derived from the Mediterranean cypress, Cupressus sempervirens. However, the ‘Stricta’ variety, known for its ornamental value, has received less attention in terms of its oil composition and potential health benefits. The objective of this research was to comprehensively analyze the chemical components and medicinal properties of the essential oil extracted from C. sempervirens ‘Stricta’ (CSSLEO) grown in Egypt. Utilizing gas chromatography–mass spectrometry (GC–MS), the investigation identified 22 compounds within CSSLEO, with α-pinene and δ-3-carene being predominant, accounting for 96.01% of the oil. In vitro assays evaluated CSSLEO’s cytotoxic effects on cancer cell lines, revealing notable anticancer potential. Additionally, the oil displayed antidiabetic properties by impeding crucial enzymes involved in glucose metabolism. Complementary in silico network pharmacology and molecular docking studies provided insights into the possible interactions between CSSLEO’s key compounds and essential proteins and pathways in cancer treatment. The results underscored CSSLEO’s intricate composition and its promising applications in cancer prevention and diabetes management. The conclusions drawn from this research underscore the need for further investigation to validate CSSLEO’s clinical effectiveness and to gain a deeper understanding of its therapeutic mechanisms, with a view to harnessing its potential in oncology and endocrinology.

Background/Objectives: This study investigates the phytochemical composition and anticancer activity of Melaleuca quinquenervia leaf essential oil (MQLEO) from Egypt. Methods: Chemical profiling was performed using GC/MS. Anticancer activity was assessed through cytotoxicity screening against multiple cancer cell lines, with a subsequent evaluation of cell migration, apoptosis, and cell cycle analysis on the most sensitive line (A549). Network pharmacology and molecular docking analyses were employed to identify potential molecular targets and pathways. Results: GC/MS analysis revealed a unique profile dominated by 1,8-cineole (31.57%), α-pinene isomers (both 1R and 1S forms, collectively 21.26%), and sesquiterpene alcohols (viridiflorol: 13.65%; ledol: 4.55%). These results diverge from prior studies, showing a 25.63% decrease in 1,8-cineole and no detectable α-terpineol, suggesting environmental, genetic, or methodological impacts on biosynthesis. In vitro tests revealed selective cytotoxicity against A549 lung cancer cells (IC₅₀ = 18.09 μg/mL; selectivity index = 4.30), meeting NCI criteria. Staurosporine was used as a positive control to validate the assays, confirming the reliability of the methods. MQLEO also inhibited cell migration (62–68% wound closure reduction) and induced apoptosis (24.32% vs. 0.7% in controls). Cell cycle arrest at the G₀-G₁ phase implicated cyclin-dependent kinase regulation. Network pharmacology identified ESR1, CASP3, PPARG, and PTGS2 as key targets, with MQLEO components engaging apoptosis, inflammation (TNF, IL-17), and estrogen pathways. Conclusions: MQLEO demonstrates promising anticancer activity through multiple mechanisms including apoptosis induction, cell cycle arrest, and migration inhibition. The multi-target activity profile highlights its potential as a therapeutic candidate for lung cancer, warranting further in vivo validation and pharmacokinetic studies to advance clinical translation.

Ulcerative colitis represents a chronic inflammatory bowel disease with limited therapeutic options due to inadequate efficacy and adverse effects of current treatments. This study investigated the therapeutic potential of Beaucarnea recurvata leaf extract (BRLE) against ulcerative colitis using integrated computational and experimental approaches to address the need for safer, multi-targeted interventions. Phytochemical profiling was performed using UPLC-ESI-MS/MS analysis. Network pharmacology and molecular docking predicted therapeutic targets and mechanisms. In vivo validation employed an acetic acid-induced ulcerative colitis rat model with BRLE treatment at 100, 200, and 400 mg/kg doses, evaluating clinical parameters, histopathology, oxidative stress markers, inflammatory cytokines, and protein expression. UPLC-ESI-MS/MS revealed diverse bioactive compounds including steroidal saponins, triterpenes, and flavonoids. Network pharmacology identified 24 hub targets, and molecular docking revealed strong binding affinities (−6.5 to −9.1 kcal/mol) between BRLE compounds and inflammatory proteins including EGFR, SRC, STAT3, and AKT1. BRLE at 200 mg/kg significantly improved disease activity, restored glutathione levels, reduced malondialdehyde, normalized IL-10 and TNF-α levels, downregulated EGFR, SRC, STAT3, and AKT1 expression, and enhanced mucosal healing with reduced inflammatory infiltration. BRLE demonstrates significant anti-inflammatory, antioxidant, and tissue-protection effects through multi-target mechanisms, representing a promising therapeutic intervention for ulcerative colitis treatment. Further studies in chronic models, pharmacokinetic assessments, and clinical trials are needed to support its translation into therapeutic use.