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.

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.

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.

Casuarina glauca branchlets' extract as a potential treatment for ulcerative colitis: chemical composition, in silico and in vivo studies.

Ulcerative colitis (UC) is an inflammatory bowel disease that is often resistant to current treatment options, leading to a need for alternative therapies. Herbal products have shown promise in managing various conditions, including UC. However, the potential of Casuarina glauca branchlets ethanolic extract (CGBRE) in treating UC has not been explored. This study aimed to analyze the chemical composition of CGBRE and evaluate its efficacy in UC treatment through in silico and in vivo experiments. LC-ESI-MS/MS was used to identify 86 compounds in CGBRE, with 21 potential bioactive compounds determined through pharmacokinetic analysis. Network pharmacology analysis revealed 171 potential UC targets for the bioactive compounds, including EGFR, LRRK2, and HSP90 as top targets, which were found to bind to key CGBRE compounds through molecular docking. Molecular docking findings suggested that CGBRE may be effective in the prevention or treatment of ulcerative colitis mediated by these proteins, where key CGBRE compounds exhibited good binding affinities through formation of numerous interactions. In vivo studies in rats with acetic acid-induced UC demonstrated that oral administration of 300 mg/kg CGBRE for 6 days reduced UC symptoms and colonic expression of EGFR, LRRK2, and HSP90. These findings supported the therapeutic potential of CGBRE in UC and suggested the need for further preclinical and clinical investigation.

Acylated pregnane glycosides from Caralluma sinaica.

Caralluma sinaica is sold on local markets of Saudi Arabia for various health benefits however no phytochemical study has specifically been performed on this species. NMR and UHPLC-ESI-TOF-MS profilings of the ethanolic extract of the whole plant reveal a very complex phytochemical composition dominated by pregnanes. Detailed information on its constituents was obtained after isolation. Six pregnane glycosides were obtained and characterized based on the extensive spectroscopic analysis (including IR, ¹H NMR, ¹³C NMR and MS data), in addition to ten known compounds (seven pregnanes and three flavonoids). The compounds were identified as 12ß-O-benzoyl-20-O-acetyl boucerin-3-O-6-deoxy-3-O-methyl-ß-D-glucopyranosyl-(1-->4)-ß-D-cymaropyranosyl-(1-->4)-ß-D-cymaropyranoside, 12ß-O-tigloyl-20-O-acetyl boucerin-3-O-ß-D-glucopyranosyl-(1-->4)-ß-D-cymaropyranoside, 12ß-O-benzoyl-20-O-acetyl boucerin-3-O-ß-D-glucopyranosyl-(1-->4)-ß-D-digitalopyranosyl-(1-->4)-ß-D-cymaropyranosyl-(1-->4)-ß-D-cymaropyranoside, 12ß-O-benzoyl-20-O-acetyl boucerin-3-O-ß-D-glucopyranosyl-(1-->4)-hevetopyranosyl-(1-->4)-ß-D-cymaropyranosyl-(1-->4)-ß-D-cymaropyranoside, 12ß-O-benzoyl-20-O-tigloyl boucerin-3-O-ß-D-glucopyranosyl-(1-->4)-ß-D-cymaropyranoside, 12ß-20-O-dibenzoyl boucerin-3-O-ß-D-glucopyranosyl-(1-->4)-ß-D-cymaropyranosyl-(1-->4)-ß-D-cymaropyranoside. Finally, the isolated compounds were evaluated for their quinone reductase induction.

3-O-trans-caffeoylisomyricadiol: a new triterpenoid from Tamarix nilotica growing in Saudi Arabia.

A detailed chemical study of the aerial parts of Tamarix nilotica (Tamaricaceae) from Saudi Arabia led to the isolation of a new pentacyclic triterpenoid, 3-O-trans-caffeoylisomyricadiol, in addition to nine known compounds. The structures of all isolated compounds were unambiguously elucidated by 1D, 2D NMR, and mass spectrometry. In the radical scavenging (DPPH) assay, 3-O-trans-caffeoylisomyricadiol exhibited potent antioxidant activity with an IC50 value of 3.56 microM, while that for quercetin (standard antioxidant) was 5.72 microM.