Phytochemical profiling of Manglietia chevalieri and its potential in attenuating pulmonary fibrosis: Insights into bioactive constituents.
A phytochemical investigation of Manglietia chevalieri (Magnoliaceae), an ornamental species has remained largely unexplored for its chemical constituents and pharmacological potential, led to the isolation and identification of 51 structurally diverse compounds. These include 20 phenylpropanoids, 12 terpenoids, and 19 alkaloids. Among them, 14 previously undescribed structures, named manglianins A-N (1-11, 12b, 13, 14), were characterized. Notably, the 3,3'-biphenyl neolignans 1-3 feature unprecedented fusions with an additional C2 or C3 unit, leading to the formation of dioxane or benzofuran rings. Compound 13 is the first sesquiterpenoid featuring a rare 3-oxabicyclo[3.3.0]octane ring. The undescribed structures and their absolute configurations were determined by extensive spectroscopic data analysis, computational calculations, and the modified Mosher's method. Given the role of chronic inflammation in driving idiopathic pulmonary fibrosis (IPF), all isolates were initially evaluated for their anti-inflammatory activity in LPS-stimulated RAW 264.7 macrophages by measuring the mRNA expression levels of CCL-2, IL-1β, and IL-6. At 1 μM, 17 isolates reduced expression of the three cytokines by more than 50%. Notably, compounds 14, 15, 28, and 40 retained significant anti-inflammatory effect at concentrations as low as 0.1 μM. Subsequent anti-fibrotic assays evaluating the expression of fibrosis markers (collagen I, fibronectin, and α-SMA) identified compounds 14, 28, 31, 33, and 40-43 as potential anti-IPF agents.