Chemical Composition and Antioxidant Activity of the Stembark Essential Oils of Two Cannabis sativa L. Cultivars from Komga, South Africa

<i>Cannabis sativa</i> L. is an aromatic medicinal plant with various biologically active classes of compounds such as cannabinoids, polyphenols, and terpenes. Unlike the widely investigated inflorescence and leaf, the stembark of <i>C. sativa</i> has been overlooked regarding its medicinal potential. This study, therefore, was aimed at determining the chemical composition and antioxidant activity of the essential oils (EOs) obtained from the fresh and dried stembark of two <i>C. sativa</i> cultivars, Lifter and Cherrywine, grown in Komga, South Africa, with a view to ascertaining the more promising cultivar. The chemical profiles of the hydro-distilled EOs were analyzed by gas chromatography-mass spectrometry (GC-MS), while an in vitro antioxidant activity assessment of the EOs was performed using DPPH and H₂O₂ spectrophotometric methods. The identified constituents from the EOs were molecularly docked against NOX2, a protein implicated in oxidative stress. The afforded EOs were colorless with a mild skunk-like odor. A total of thirty-two constituents were identified in both fresh and dry oils from the Lifter cultivar while the Cherrywine cultivar contained a total of forty-two constituents. The EOs of both cultivars contained twenty compounds, notably Cannabidiol (0.25-85.03%), Caryophyllene oxide (1.27-19.58%), Caryophyllene (0.64-16.61%), Humulene (0.37-8.15%), Octacosane (3.37-6.55%), Humulene-1,2-epoxide (0.45-5.78%), Nerolidol (0.32-4.99%), Palmitic acid (1.45-4.45%), Tetracosane (1.75-2.91%), Dronabinol (0.86-2.86%), Cannabinol (0.54-1.64%), 7-epi-γ-eudesmol (0.53-1.00%), Guaiol (0.37-0.66%), Linoleic acid (0.22-0.60%), γ-Selinene (0.15-0.48%), β-Eudesmol (0.34-0.50%), and Linalool (0.24-0.30%). The dried Lifter stembark oil (DLSO) gave the best antioxidant activity among the four investigated cannabis oils, exhibiting the lowest IC₅₀ values of 21.68 ± 1.71 and 26.20 ± 1.34 µg/mL against DPPH and H₂O₂ radicals, respectively. The notable antioxidant activity of the DLSO may be attributed to the higher number (30) of constituents compared to the fresh Lifter stembark oil (LSO) with 11 constituents. Additionally, the DLSO showed a unique chemical profile comprising monoterpenes, oxygenated and hydrocarbon sesquiterpenes. Further in silico studies on the putative constituents in the Lifter cultivar revealed Cannabinol, Cannabidiol, and Linalool as the promising constituents based on their higher binding energy scores of -9.7, -8.5, and -6.5 kcal/mol, respectively, compared to L-Ascorbic acid (-5.7 kcal/mol). It can be inferred from this study that the EOs from the stembark of <i>C. sativa</i> contain promising compounds, such as Cannabinol, Cannabidiol, and Linalool, which might be responsible for the displayed antioxidant activity of the oils. Thus, the study findings underscore the biological importance of <i>C. sativa</i> stembark in the management of oxidative stress-related conditions.