Antioxidant and Leishmanicidal Evaluation of Pulicaria Inuloides Root Extracts: A Bioguided Fractionation

Leishmaniasis remains a major world health problem, and in particular, Algeria ranks second for the incidence of cutaneous leishmaniasis. Pulicaria inuloides is a well-known Arabian Peninsula medicinal plant. In the present study, the chloroform, ethyl acetate and n-butanol extracts from the roots of Pulicaria inuloides were analyzed for antioxidant activity and its correlation with the total phenolic and flavonoid contents. The highest antioxidant activity using a DPPH assay was showed by the ethyl acetate extract (IC₅₀ 4.08 µg/mL), which also had the highest total phenolic content (307.12 µgAGE). Furthermore, P. inuloides root extracts were evaluated against Leishmania amazonensis and Leishmania donovani. The results highlighted the chloroform extract as the most active one against both tested Leishmania strains. A bioguided fractionation of the chloroform extract led to the isolation of (8R:8S)-(75:25 er)-10-isobutyryloxy-8,9-epoxy-thymol isobutyrate as the main bioactive component, showing a potent leishmanicidal activity on L. amazonensis promatigote and amastigote stages (IC₅₀ 5.03 and 2.87 µM, respectively) and a good selectivity index on murine macrophages (CC₅₀ 19.37 µM). This study provides the first report of the antioxidant and leishmanicidal activities of P. inuloides root extracts and the results point to this species as a source of potential bioactive agents.