Oleocanthal as a Promising Natural Therapeutic Agent: the Experimental Leishmaniasis Paradigm

Oleocanthal (OC) is a phenolic compound of Extra Virgin Olive Oil (EVOO), the main source of fatty acids in the Mediterranean diet that is associated with beneficial health effects such as reduced incidence of cardiovascular mortality and cancer. OC is responsible for the localized irritation in the oropharangeal region, is homologous with the non‐steroidal anti‐inflammatory drug ibuprofen and several studies evidenced relevant pharmacological properties of OC in different pathogenic processes. Our group has previously elucidated the anti‐leishmanial effect of Total Phenolic Fraction derived from EVOO and of the phenolic compound Oleuropein. Current study aimed to evaluate the effect of OC in murine experimental models of cutaneous and visceral leishmaniasis since there is no effective vaccine and the chemotherapeutic treatments have serious drawbacks such as toxicity, parasite resistance and high cost. BALB/c mice were infected either subcutaneously in the footpad with 10 6 L. major promastigotes (Cutaneous Model ‐ CM) or intravenously in the tail vein with 10 7 L. infantum promastigotes (Visceral Model ‐ VM), according to EC regulation conformed by FASEB Statement of Principles for the use of Experimental Animals. At 7 days post infection, mice were intraperitonealy treated with 5 and 10 mg/kg body weight of OC, 3 days per week for 5 weeks. Mice of the positive control group received orally 15 mg/kg b.w of the reference drug miltefosine (HePC), for 25 days. In the CM, results demonstrate significant reduction of the footpad swelling in OC‐treated mice along with the reduction of parasite load in the popliteal lymph nodes, 1 month post‐treatment termination. Correspondingly, in the VM, OC promoted a severe reduction of parasite burden in target organs, liver and spleen at 10 days post‐treatment termination. Moreover, in order to validate the profile of cytokines induced by OC treatment, intracellular cytokine production in splenocytes of all experimental groups was determined for IL‐4 (Th2‐type cytokine) and IL‐12 (Th1‐type cytokine) at 48h post Soluble Leishmania Antigen in vitro re‐stimulation and revealed that OC was able to stimulate important reduction in IL‐4 production by CD4 + T cells in both CM and VM, while the IL‐12 production was equal in all experimental groups. Furthermore, specific antibodies of both IgG1 and IgG2α isotypes, were detected in the plasma of OC‐treated mice. These data indicate that OC treatment resulted in the induction of a mixed Th1/Th2 immune response moderately polarized towards Th1 type that effectively mediated the elimination of parasitic spread in both disease models. Therefore, OC appears as a potential therapeutic agent into the leishmaniasis drug discovery pipeline. Support or Funding Information This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .