Oxygenated sesquiterpenes, molecular docking, and the trait-linked occurrence of essential oil in Knema angustifolia (Roxb.) Warb (Myristicaceae).

[Display omitted] • Essential oil found in folk medicinal plant Knema angustifolia for the first time containing oxygenated sesquiterpenes. • Site specific molecular docking of τ-Cadinol and δ-Cadinol showed high tau binding affinity (-6.2 Kcal/mol) like FDA approved drug. • Phylogenetic frame work was reconstructed with K. angustifolia and allied species using plastid genes viz., psbA-trnH, rbcL and matK. • Traced diagnostic species traits onto tree topology reflected presence of essential oil as shared ancestral trait. • Maxent modelling predicted suitable habitat for long-term conservation in NE India and Western Himalayas. The folk medicinal plant Knema angustifolia (Roxb.) Warb. of Myristicaceae is reported with the essential oil (0.02±0.001 - 0.04±0.01%) in leaves and twigs respectively, for the first time. The GC-MS analysis of essential oil found 15 oxygenated sesquiterpenes viz., Globulol (30.83-35.46%), Spathulenol (21.46-23.98%), Viridiflorol (6.24-12.40%) and others. Several species under the family Myristicaceae had been used in neurodegenerative diseases. The site-specific docking of the markers against tau protein, the major causal factor for neurodegenerative diseases were carried out which found biomarkers viz., α-Cadinol, δ-Cadinol, epi -Cubenol, Neointermedeol, Shyobunol, and τ-Cadinol with moderate to high binding affinity (-5.1 to -6.2 Kcal/mol). The markers followed ADMET parameters including Human Intestinal Absorption, Blood Brain Barrier, CNS permeability, and Lipinski rule of five, and were found as moderately bioactive. τ-Cadinol and δ-Cadinol showed high binding affinity (-6.2 Kcal/mol) like Galantamine, an FDA-approved drug. Moreover, τ-Cadinol and δ-Cadinol showed moderate activity as nuclear receptors, enzyme inhibitors, and ion channel modulators and exhibited potential as a base structure to develop candidate oral drugs. The potential of trait-linked occurrence of essential oil among K. angustifolia and allied species were assessed through ancestral reconstruction using Mesquite ver. 3.61 upon Bayesian consensus tree of plastid genes viz., psbA-trnH, rbcL, and matK. The essential oil was found as a shared ancestral trait in K. angustifolia. For the long-term conservation of K. angustifolia, the MaxEnt modeling was carried out which predicted climate-suitable habitat in NE India and Western Himalayas. [ABSTRACT FROM AUTHOR]