Research Information System
South African Journal of Botany, vol.184, pp.603-616, 2025 (SCI-Expanded)
Taxodium distichum (bald cypress) is a known traditional remedy for treating various inflammatory conditions, such as lesions of the skin, inflammation, and rheumatic pain. Historically, infusions and ointments that are made from different organs of Taxodium were used for the treatment of wounds, gout, hemorrhoids, ulcers, and rheumatism. The Aztecs used different Taxodium organs for the treatment of burns, sores, and ulcers. Chemical profiling of leaves, cones, and woody stems extracts of two varieties of Taxodium distichum (L.) Rich were analyzed via UPLC/MS/MS. Real-time PCR was used to evaluate the impact of the tested samples on the gene expression of four pro-inflammatory markers (TNF-α, IL-1β, IL-6, and IFN-γ). Chemometric analysis was done using SIMCA® (multivariate data analysis software), and it is coupled to mass spectrometry and biological activity results to investigate the influence of different organs on the chemical profile and activity of the tested extracts. The biomarkers identified through OPLS analysis were docked into potential target pockets to explore their possible interaction patterns using the Schrodinger® suite. Molecular dynamics simulations were done with the same program. Sixty-two metabolites of different chemical classes were identified. Coupling UPLC/MS/MS results to chemometric analysis revealed that organs have a more pronounced effect on sample clustering than the variety effect. MTT test was carried out, and all samples showed a significantly high safety with a range of IC50 values (46 ± 1.04 −85 ± 1.1 µg/mL). Real-time PCR was used to evaluate the impact of the tested samples on the gene expression of four pro-inflammatory markers (TNF-α, IL-1β, IL-6, and IFN-γ). The strongest inhibition of TNF-α and IL-1β gene expression was seen in woody stem extracts of T. distichum var. distichum (0.38 ± 0.05 folds and 0.79 ± 0.07 folds, respectively). In the meantime, T. distichum var. pendens woody stem extracts considerably reduced the expression of the IL-6 gene (1.1 ± 0.11 times). Conversely, T. distichum var. distichum leaf and cone extracts dramatically reduced the expression of the IFN-γ gene (1.3 ± 0.15 and 1.2 ± 0.17 folds, respectively). Coefficient plots unveiled that gallic acid, nicotiflorin, 4-hydroxybenzoic acid, icariside E4, amentoflavone, agatholal, and sesamin were the bioactive metabolites regarding the inhibition of IL-1β and TNF-α gene expression. The docking results revealed significant interactions between icariside E4, 4-Hydroxybenzoic acid, and piroxicam with TNF-α. Molecular dynamic simulation showed that both compounds remained stable within the active site of TNF-α throughout the 100 ns simulation, reinforcing the stability and compatibility of the binding interactions. Taxodium has different organs that are rich in bioactive metabolites, so they can be considered important sources of anti-inflammatory metabolites. Results are a first step in proving the traditional use of Taxodium as an anti-inflammatory agent.