Production and bioprocessing of epothilone B from Aspergillus niger, an endophyte of Latania loddegesii, with a conceivable biosynthetic stability: anticancer, anti-wound healing activities and cell cycle analysis.

Epothilones are one of the common prescribed anticancer drugs for solid tumors, for their exceptional binding affinity with ß-tubulin microtubule, stabilizing their disassembly, causing an ultimate arrest to the cellular growth. Epothilones were initially isolated from Sornagium cellulosum, however, their extremely slow growth rate and low yield of epothilone is the challenge. So, screening for a novel fungal endophyte dwelling medicinal plants, with higher epothilone productivity and feasibility of growth manipulation was the objective. Aspergillus niger EFBL-SR OR342867, an endophyte of Latania loddegesii, has been recognized as the heady epothilone producer (140.2 µg/L). The chemical structural identity of the TLC-purified putative sample of A. niger was resolved from the HPLC, FTIR and LC-ESI-MS/MS analyses, with an identical molecular structure of the authentic epothilone B. The purified A. niger epothilone B showed a resilient activity against MCF-7 (0.022 µM), HepG-2 (0.037 µM), and HCT-116 (0.12 µM), with selectivity indices 21.8, 12.9 and 4, respectively. The purified epothilone B exhibited a potential anti-wound healing activity to HepG-2 and MCF-7 cells by ~ 54.07 and 60.0%, respectively, after 24 h, compared to the untreated cells. The purified epothilone has a significant antiproliferative effect by arresting the cellular growth of MCF-7 at G2/M phase by ~ 2.1 folds, inducing the total apoptosis by ~ 12.2 folds, normalized to the control cells. The epothilone B productivity by A. niger was optimized by the response surface methodology, with ~ 1.4 fold increments (266.9 µg/L), over the control. The epothilone productivity by A. niger was reduced by ~ 2.4 folds by 6 months storage as a slope culture at 4 °C, however, the epothilone productivity was slightly restored with ethylacetate extracts of L. loddegesii, confirming the plant-derived chemical signals that partially triggers the biosynthetic genes of A. niger epothilones. So, this is the first report emphasizing the metabolic potency of A. niger, an endophyte of L. loddegesii, to produce epothilone B, that could be a new platform for industrial production of this drug.

Production and bioprocessing of Taxol from Aspergillus niger, an endophyte of Encephalartos whitelockii, with a plausible biosynthetic stability: antiproliferative activity and cell cycle analysis.

The biosynthetic potency of Taxol by fungi raises their prospective to be a platform for commercial production of Taxol, nevertheless, the attenuation of its productivity with the fungal storage, is the challenge. Thus, screening for a novel fungal isolate inhabiting ethnopharmacological plants, with a plausible metabolic stability for Taxol production could be one of the most affordable approaches. Aspergillus niger OR414905.1, an endophyte of Encephalartos whitelockii, had the highest Taxol productivity (173.9 µg/L). The chemical identity of the purified Taxol was confirmed by HPLC, FTIR, and LC-MS/MS analyses, exhibiting the same molecular mass (854.5 m/z) and molecular fragmentation pattern of the authentic Taxol. The purified Taxol exhibited a potent antiproliferative activity against HepG-2, MCF-7 and Caco-2, with IC50 values 0.011, 0.016, and 0.067 µM, respectively, in addition to a significant activity against A. flavus, as a model of human fungal pathogen. The purified Taxol displayed a significant effect against the cellular migration of HepG-2 and MCF-7 cells, by ~ 52-59% after 72 h, compared to the control, confirming its interference with the cellular matrix formation. Furthermore, the purified Taxol exhibited a significant ability to prompt apoptosis in MCF-7 cells, by about 11-fold compared to control cells, suppressing their division at G2/M phase. Taxol productivity by A. niger has been optimized by the response surface methodology with Plackett-Burman Design and Central Composite Design, resulting in a remarkable ~ 1.6-fold increase (279.8 µg/L), over the control. The biological half-life time of Taxol productivity by A. niger was ~ 6 months of preservation at 4 â„ƒ, however, the Taxol yield by A. niger was partially restored in response to ethyl acetate extracts of E. whitelockii, ensuring the presence of plant-derived signals that triggers the cryptic Taxol encoding genes.

Unveiling the Bioactive Efficacy of Cupressus sempervirens 'Stricta' Essential Oil: Composition, In Vitro Activities, and In Silico Analyses.

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.

Chamaecyparis lawsoniana Leaf Essential Oil as a Potential Anticancer Agent: Experimental and Computational Studies.

Cancer remains one of the leading causes of death worldwide, affected by several factors including oxidative stress; and although conventional synthetic medicines have been used to treat cancer, they often result in various side effects. Consequently, there is a growing need for newer, safer and more effective alternatives, such as natural plant products. Essential oils (EOs) are one such alternative, offering a wide range of bioactivities, including antibacterial, antiviral, antioxidant, and anticancer properties. Accordingly, the objective of the present study was to investigate the chemical composition, as well as the antioxidant and anticancer properties of the leaf essential oil of Chamaecyparis lawsoniana (CLLEO) belonging to the Cupressaceae family. Totally, 59 constituents were identified by gas chromatography-mass spectrometry (GC-MS) analysis. cis-Abienol, trans-ferruginol, α-cadinol, δ-muurolene and α-pinene were the major components. The in vitro cytotoxicity study against human breast (MCF-7), colon (HCT-116), lung (A-549), hepatocellular (HepG-2) carcinoma cells using MTT assay indicated a promising cytotoxic activity against all the tested cancer cells, particularly HepG-2, with significant selectivity indices. CLLEO exhibited weak antioxidant activity according to the DPPH, ABTS and FRAP assays. In silico docking of these constituents against the epidermal growth factor receptor (EGFR), the myeloid cell leukemia-1 (Mcl-1) and caspase-8 using Molecular Operating Environment (MOE) software demonstrated good binding affinities of the components with the active site of these targets. These findings suggested using CLLEO, or its individual components, as a potentially viable therapeutic option for managing cancerous conditions.

Potential Hepatoprotective Effects of Chamaecyparis lawsoniana against Methotrexate-Induced Liver Injury: Integrated Phytochemical Profiling, Target Network Analysis, and Experimental Validation.

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.

Antihepatotoxic activity and chemical constituents of Buddleja asiatica Lour.

A new natural compound, named 6-O-(3",4"-dimethoxycinnamoyl) catalpol, was isolated from the defatted alcoholic extract of the flowering parts of Buddleja asiatica Lour. (family Scrophulariaceae). Other separated known compounds included steroids (beta-sitosterol, stigmasterol, stigmasterol-O-glucoside, beta-sitosterol-O-glucoside), iridoid glucosides (methyl catalpol, catalpol, aucubin), phenylpropanoids (isoacteoside and acteoside), a triterpene saponin (mimengoside A), flavonoids (diosmin and linarin) in addition to the free sugars mannitol and sucrose. The structures of the isolated compounds were established by 1H and 13C NMR and mass spectrometry. Furthermore, the polar fraction of the flowering parts and the roots showed substantial antihepatotoxic activity comparable to that of the lignan silymarin.