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

## TL;DR

This study tracked how the chemical makeup and antileishmanial activity of Vernonanthura polyanthes essential oils changed over two years, identifying key compounds linked to effectiveness.

## Contribution

The study reveals seasonal biomarkers in Vernonanthura polyanthes essential oils that correlate with antileishmanial activity and low cytotoxicity.

## Key findings

- Hydrocarbon sesquiterpenes like β-caryophyllene and β-pinene are strongly correlated with antileishmanial activity.
- Oxygenated sesquiterpenes in late 2024 reduced potency despite high concentrations.
- Multivariate analysis explained 61% of the variance in activity, linking chemical profiles to biological effects.

## Abstract

The present study investigated the chemical composition and antileishmanial activity of Vernonanthura polyanthes 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 Leishmania (L.) infantum 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 V. polyanthes and highlight key biomarkers that may guide future pharmacological and biotechnological applications.