Comparative Foliar Elicitation with Yeast Extract and Sodium Butyrate Reshapes Terpenoid Metabolism in Salvia officinalis

The industrial utilization of Salvia officinalis L. depends on cost-effective and scalable strategies for improving the consistent production of high-value bioactive terpenoids. In this study, two non-transgenic foliar elicitation strategies, yeast extract (YE, 2 g L -1 ) and sodium butyrate (NaB, 25 and 50 mM), were evaluated for their ability to reprogram terpenoid metabolism in S. officinalis . Integrated GC–MS metabolite profiling and qRT-PCR analysis showed that the two elicitors induced distinct transcriptional and metabolic responses. YE promoted coordinated upregulation of MVA and MEP pathway genes, resulting in moderate enrichment of β-caryophyllene (4.28-fold) and ferruginol (2.92-fold) while largely preserving the native monoterpene-rich chemotype. In contrast, NaB induced a markedly asymmetric transcriptional response, characterized by strong upregulation of the sesquiterpene synthase SoHUMS (>15-fold), together with substantial accumulation of β-caryophyllene (>10-fold; 31% of the total extract) and ferruginol (3.55-fold; 4.60% of the total extract). NaB treatment was also associated with the appearance of α-humulene, caryophyllene oxide, α-gurjunene, and 14β-pregnane, suggesting activation of otherwise low-abundance sesquiterpene- and sterol-associated metabolic pathways. These metabolic changes were accompanied by enhanced antiproliferative activity of the extracts against MCF-7 breast cancer cells. Molecular docking and ADMET analyses provided supportive, hypothesis-generating evidence that ferruginol and other NaB-enriched terpenoids may contribute to this activity. Overall, these findings identify sodium butyrate as a non-transgenic foliar elicitor capable of redirecting isoprenoid metabolism in S. officinalis and provide a practical framework for improving the phytochemical quality of medicinal plant biomass.