Seasonal Dynamics of the Essential Oil Constituents from the Aerial Parts of Vernonanthura polyanthes (Asteraceae) and Their Anti-Leishmania infantum Potential: A Multimethodological Approach

The present study investigated the chemical composition and antileishmanial activity of <i>Vernonanthura polyanthes</i> essential oils over a two-year monitoring period (monthly collection from January/2023 to December/2024). The oils exhibited a high concentration of hydrocarbon sesquiterpenes, primarily germacrene D, β-caryophyllene, α-humulene, and bicyclogermacrene, whereas the levels of monoterpenes and oxygenated sesquiterpenes fluctuated seasonally. Activity against promastigotes of <i>Leishmania</i> (<i>L.</i>) <i>infantum</i> was strongly dependent on the essential oil chemical profile, with consistently low EC₅₀ values seen in months with a higher content of hydrocarbon sesquiterpenes. However, significant increases in oxygenated sesquiterpenes at the end of 2024 were accompanied by a reduction in potency. Cytotoxicity against NCTC cells remained low in most samples (CC₅₀ > 200 µg/mL). Multivariate statistical analysis was applied to investigate the relationship between the chemical composition of studied essential oils and their antileishmanial activity. Partial Least Squares (PLS) modeling based on key volatile markers (VIP > 1.0) revealed a significant correlation between constituent profiles and biological potency, explaining 61% of the activity variance (R² = 0.61). Regression coefficients identified β-caryophyllene and β-pinene as major contributors to enhanced activity, while β-bourbonene was associated with reduced potency. Seasonal evaluation showed that β-caryophyllene provides stable baseline activity, whereas peaks in β-pinene correspond to increased potency, suggesting a positive correlation associated with enhanced potency between these constituents. Integrated EC₅₀ and CC₅₀ models further demonstrated that β-pinene and β-caryophyllene combine desirable features of strong activity and low cytotoxicity. These findings clarify the metabolic drivers of seasonal bioactivity in <i>V. polyanthes</i> and highlight key biomarkers that may guide future pharmacological and biotechnological applications.