Assessment of the antiprotozoal activity of Pulicaria inuloides extracts, an Algerian medicinal plant: leishmanicidal bioguided fractionation

Abstract

The lack of an effective chemotherapy for treatment of protozoan disease urges a wide investigation for active compounds, and plant-derived compounds continue to provide key leads for therapeutic agents. The current study reports the in vitro antiprotozoal evaluation of the Algerian medicinal plant Pulicaria inuloides against Leishmania amazonensis, Trypanosoma cruzi, and Acanthamoeba castellanii str. Neff. All the extracts from the aerial part showed to be present a higher leishmanicidal activity than anti-Acanthamoeba or Trypanosoma. Therefore, bioguided fractionation of the active CHCl extract led to the isolation and characterization of the flavonol, quercetagetin-3,5,7,3'-tetramethyl ether (1) as the main component. The structure of compound 1 was established by extensive 1D and 2D NMR spectroscopic analysis (COSY, HSQC, HMBC, and ROESY experiments), chemical transformation (derivatives 2 and 3), and comparison with data in the literature. Compound 1 and derivatives 2 and 3 were further evaluated against the promastigote and amastigote stage of L. amazonensis. Compounds 1-3 exhibited moderate leishmanicidal activity with IC values ranging from 0.234 to 0.484 mM and from 0.006 to 0.017 mM for the promastigote and amastigote forms, respectively, as well as low toxicity levels on macrophages (CC ranging from 0.365 to 0.664 mM). This study represents the first report of the antiprotozoal evaluation of Pulicaria inuloides, and the results highlight this species as a promising source of leishmanicidal agents.

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

“…Our previous works reported the in vitro antiprotozoal evaluation of extracts from the aerial part of P. inuloides, and the characterization of quercetagetin-3,5,7,3'-tetramethyl ether as the main component of the active CHCl 3 extract [19]. In the present work, and as a continuation of the P. inuloides medicinal plant research, the antioxidant activity, total phenolic and flavonoid contents, and leishmanicidal properties of P. inuloides roots are reported.…”

“…On the other hand, sub-fraction F1B3 showed a potent leishmanicidal effect with IC 50 values of 5.03 ± 0.29 µM and 4.65 ± 0.10 µM on both Leishmania strains, respectively, even somewhat higher on L. amazonensis that Miltefosine used as the reference drug (IC 50 values of 6.48 µM and 3.32 µM on L. amazonensis and L. donovani, respectively, Table 4 and Figure 2). Moreover, evaluation of this active sub-fraction on murine macrophages (CC 50 19.37 µM ± 0.23 µg/mL) in the search for selectivity indicated a moderate selective index (SI), with values of 3.9 and 4.2 for these Leishmania strains, respectively [22]. Activity assays against L. amazonensis intracellular amastigotes (Table 4) revealed that F1B3 was also more potent (IC50 2.87 µM) that the reference drug, miltefosine (IC50 3.12 µM), which increases the interest of this active sub-fraction as potential leishmanicidal agent.…”

“…To our knowledge, this is the first report of thymol derivative 1 in Pulicaria genus. Previously, the leishmanicidal bioguided fractionation of the active chloroform extract from the aerial part of P. inuloides led to the isolation of quercetagetin-3,5,7,3'-tetramethyl ether as the main bioactive component, exhibiting a moderate leishmanicidal activity with an IC 50 value of 0.483 mM on L. amazonensis [19]. Furthermore, the present study reveals that a thymol derivative, the major component from the roots of this species, is responsible for the leishmanicidal activity.…”

Spiralyde A, an Antikinetoplastid Dolabellane from the Brown Alga Dictyota spiralis

“…The cytotoxicity of active compounds was evaluated in murine macrophage J774.A1 cell line (ATCC # TIB-67). Different concentrations were incubated for 24 h and viability was determined with the Alamar Blue method using dose-response curves to obtain the CC 50 [25].…”

Withanolides from Withania aristata as Antikinetoplastid Agents through Induction of Programmed Cell Death

“…Macrophages were plated and at 10 5 macrophages/well and, subsequently, serial dilution of samples were added to the plates. After 24 h of incubation cell viability was determined by the alamarBlue ® [28].…”