Salvia limbata extracts and essential oil as a novel source of bioactive agents: metabolomic fingerprint, in vitro, in silico and network pharmacological perspectives

The genus Salvia has received considerable attention and has been studied extensively owing to its rich polyphenolic content. In the present study, Salvia limbata essential oil (EO) and extracts from its aerial parts and roots were used to examine the chemical profile and biological activities. The chemical profiles of the EO and extracts were determined using GC-MS and UHPLC-HRMS analyses, respectively. The biological activities were assessed using six antioxidant assays, nine enzyme inhibitions, and four cell lines for cytotoxicity and antiviral properties. In the essential oils, 8,13-epoxy-15,16-dinorlabd-12-ene (16.87%) and phytol (7.84%) were the dominant compounds. UHPLC-HRMS revealed that flavonoids were the main groups in the tested extracts, as well as phenolic acids (hydroxycinnamic and hydroxybenzoic acids) and caffeic acid oligomers. Among the extracts, the ethyl acetate (EA) root extract had the highest antioxidant activity, with values of 503.32 mg TE per g, 425.44 mg TE per g, and 349.34 mg TE per g in the CUPRAC, ABTS, and FRAP assays, respectively. The aerial-part ethanol/water extract showed higher antioxidant capacity in the CUPRAC, ABTS, and DPPH assays. The EO showed strong enzyme inhibition, notably against AChE, BChE, tyrosinase, and lipase, and exhibited significantly higher inhibitory activity against CA I (IC₅₀ = 10.93 µg mL⁻¹) and CA II (IC₅₀ = 27.07 µg mL⁻¹) compared to all solvent extracts. The aerial-part hexane, ethyl acetate, and ethanolic extracts of S. limbata were moderately cytotoxic to non-cancerous and all cancer-derived cell lines, while the extract obtained from the leaves with 70% ethanol was not toxic to non-cancerous VERO cells but showed weak to moderate cytotoxicity to the other cell lines. Ethanolic and aqueous ethanolic aerial-part extracts, as well as the EO, reduced the HHV-1-induced cytopathic effect, but the titration assay indicated that the highest inhibition of virus infectivity was found for the aqueous ethanolic extract. To gain further insights into the molecular mechanisms underlying these biological activities, major identified metabolites were evaluated using network pharmacology, molecular docking, and molecular dynamics simulations. These results emphasize the significant medicinal value of S. limbata, which exhibits promising antioxidant, enzyme-inhibiting, and anticancer activities.