Anthelmintic, Antibacterial and Cytotoxicity Activity of Imidazole Alkaloids fromPilocarpus microphyllusLeaves

Abstract

Pilocarpus microphyllus Stapf ex Wardlew (Rutaceae), popularly known as jaborandi, is a plant native to the northern and northeastern macroregions of Brazil. Several alkaloids from this species have been isolated. There are few reports of antibacterial and anthelmintic activities for these compounds. In this work, we report the antibacterial and anthelmintic activity of five alkaloids found in P. microphyllus leaves, namely, pilosine, epiisopilosine, isopilosine, epiisopiloturine and macaubine. Of these, only anthelmintic activity of one of the compounds has been previously reported. Nuclear magnetic resonance, HPLC and mass spectrometry were combined and used to identify and confirm the structure of the five compounds. As regards the anthelmintic activity, the alkaloids were studied using in vitro assays to evaluate survival time and damaged teguments for Schistosoma mansoni adult worms. We found epiisopilosine to have anthelmintic activity at very low concentrations (3.125 μg mL ); at this concentration, it prevented mating, oviposition, reducing motor activity and altered the tegument of these worms. In contrast, none of the alkaloids showed antibacterial activity. Additionally, alkaloids displayed no cytotoxic effect on vero cells. The potent anthelmintic activity of epiisopilosine indicates the potential of this natural compound as an antiparasitic agent. Copyright © 2017 John Wiley & Sons, Ltd.

Imidazole alkaloids inhibit the pro-inflammatory mechanisms of human neutrophil and exhibit anti-inflammatory propertiesin vivo

“…Neither alkaloids reduced the mitochondrial activity, measured by the MTT test, or affect the cell membrane permeability, measured by the LDH enzyme activity. The lack of toxicity of these alkaloids has been previously described in Vero cells and peritoneal macrophages …”

“…The lack of toxicity of these alkaloids has been previously described in Vero cells and peritoneal macrophages. [12,16] The treatment of neutrophils with EPI and EPIIS significantly inhibited the degranulation of PMA-or fMLPinduced activation, as measured by the release of MPO. The abundant supply of MPO equips neutrophils for their role in the innate immune defence against microbes, converting the H 2 O 2 produced by the NADPH oxidase into the potent microbicide HOCl.…”

“…Recently, a chemical study of the waste produced by pilocarpine extraction from P. microphyllus allowed the isolation of two imidazole alkaloids structurally similar: epiisopilosine (EPIIS) and epiisopiloturine (EPI) (Figure ). EPI has several pharmacological properties, including antiparasitic, antibacterial, antiproliferative activities . Anti‐inflammatory and antinociceptive activities were evaluated in acute inflammation and nociception models (1 mg/kg, i.p.)…”

“…On the other hand, there are very few studies exploring EPIIS. EPIIS acts as a stimulant of the peripherical parasympathetic nervous system and as anthelmintic . Despite de structural similarity between EPI and EPIIS (Figure ), the latter was not investigated as an anti‐inflammatory drug yet.…”

“…EPI has several pharmacological properties, including antiparasitic, [9,11] antibacterial, antiproliferative activities. [12] Anti-inflammatory and antinociceptive activities were evaluated in acute inflammation and nociception models (1 mg/kg, i.p.) such as carrageenaninduced paw oedema, acetic acid-induced writhing, hot plate and the formalin tests in mice.…”