Exploring the Immunotherapeutic Potential of Oleocanthal against Murine Cutaneous Leishmaniasis

Abstract

Leishmaniasis is a major tropical disease with increasing global incidence. Due to limited therapeutic options with severe drawbacks, the discovery of alternative treatments based on natural bioactive compounds is important. In our previous studies we have pointed out the antileishmanial activities of olive tree-derived molecules. In this study, we aimed to investigate the in vitro and in vivo antileishmanial as well as the in vivo immunomodulatory effects of oleocanthal, a molecule that has recently gained increasing scientific attention. Pure oleocanthal was isolated from extra virgin olive oil through extraction and chromatography techniques. The in vitro antileishmanial effects of oleocanthal were examined with a resazurin-based assay, while its in vivo efficacy was evaluated in Leishmania major-infected BALB/c mice by determining footpad induration, parasite load in popliteal lymph nodes, histopathological outcome, antibody production, cytokine profile of stimulated splenocytes and immune gene expression, at three weeks after the termination of treatment. Oleocanthal demonstrated in vitro antileishmanial effect against both L. major promastigotes and intracellular amastigotes. This effect was further documented in vivo as demonstrated by the suppressed footpad thickness, the decreased parasite load and the inflammatory cell influx at the infection site. Oleocanthal treatment led to the dominance of a Th1-type immunity linked with resistance against the disease. This study establishes strong scientific evidence for olive tree-derived natural products as possible antileishmanial agents and provides an adding value to the scientific research of oleocanthal.

Direct In Vitro Comparison of the Anti-Leishmanial Activity of Different Olive Oil Total Polyphenolic Fractions and Assessment of Their Combined Effects with Miltefosine

“…At this point, it must be highlighted that OLEA and OLEO comprise derivatives (precursors) of HT and T, respectively, and could facilitate as prodrugs releasing HT and T in a biological system after metabolization (hydrolysis). These findings are consistent with one of our previous studies, which demonstrated the remarkable in vitro and in vivo anti-leishmanial properties of pure OLEO [ 26 ]. Moreover, this is the first study that describes the nature of interactions between the phenolic extracts of EVOO and miltefosine against both a viscerotropic and a dermotropic Leishmania strain.…”

“…According to the EU Health Claim Labeling Regulation, olive oil polyphenols are therefore listed among food substances with attributed health claims (432/2012) [ 21 , 22 ]. Our group has showcased the anti-leishmanial properties of olive oil phenolic compounds by demonstrating that pure oleuropein and oleocanthal (OLEO) exert anti-leishmanial properties in vitro and promote in vivo efficacy in murine experimental models of VL and CL [ 23 , 24 , 25 , 26 ]. In addition, we have reported that TPF exhibits chemotherapeutic anti-leishmanial activity in vitro and in vivo [ 27 , 28 ].…”

Pharmacokinetics and Metabolism Investigation of Oleocanthal

“…In the present study, oleocanthal ( 1 ) was administered IP at the concentration of 5 mg/kg to mice. The indicated dose and method of administration were selected according to literature data and the most used study design in in vivo studies of 1 ,− to generate meaningful metabolism-related data that could be extrapolated to the claimed effects. Additionally, the time points of the study (0, 5, 15, and 30 min and 1, 4, 6, 8, 12, and 24 h) were a basic element of the current study design.…”