Leishmanicidal activity of Cecropia pachystachya flavonoids: Arginase inhibition and altered mitochondrial DNA arrangement

Abstract

The plant Cecropia pachystachya Trécul is widely used in Brazilian ethnomedicine to treat hypertension, asthma, and diabetes. Arginase is an enzyme with levels that are elevated in these disorders, and it is central to Leishmania polyamine biosynthesis. The aims of this study were to evaluate antileishmanial activity and inhibition of the arginase enzyme by C. pachystachya extracts, and to study changes in cellular organization using electron microscopy. The ethanol extract of C. pachystachya was tested on Leishmania (Leishmania) amazonensis promastigote survival/proliferation and arginase activity in vitro. Qualitative ultrastructural analysis was also used to observe changes in cell organization. The major bioactive molecules of the ethanol extract were characterized using liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS). The ethyl acetate fraction of the ethanol extract diminished promastigote axenic growth/survival, inhibited arginase activity, and altered a mitochondrial kinetoplast DNA (K-DNA) array. The bioactive compounds of C. pachystachya were characterized as glucoside flavonoids. Orientin (9) (luteolin-8-C-glucoside) was the main component of the methanol-soluble ethyl acetate fraction obtained from the ethanol extract and is an arginase inhibitor (IC50 15.9 μM). The ethyl acetate fraction was not cytotoxic to splenocytes at a concentration of 200 μg/mL. In conclusion, C. pachystachya contains bioactive compounds that reduce the growth of L. (L.) amazonensis promastigotes, altering mitochondrial K-DNA arrangement and inhibiting arginase.

Evaluation of the antiplasmodial and leishmanicidal potential of Myrciaria dubia (Myrtaceae) extract

“…Cruz et al (52) demonstrated that flavonoids, in addition to altering the arrangement of mitochondrial deoxyribonucleic acid (DNA), also inhibit the enzyme arginase, which participates in the parasite's polyamine biosynthesis. Fonseca-Silva et al (53) demonstrated that treatment of L. amazonensis with quercetin, a flavonoid most commonly found in plants, increases the production of reactive oxygen species (ROS), promotes mitochondrial dysfunction in the parasite, and inhibits cell growth.…”

Cecropia pachystachya extract attenuated the renal lesion in 5/6 nephrectomized rats by reducing inflammation and renal arginase activity

“…The profile of the constituents from Cecropia pachysatachya FCP extract was performed using liquid chromatography-mass spectra (LC-MS) using Esquire 3000 Plus (Bruker Daltonics) as described previously (Cruz et al, 2013).…”

Differentiation of the phenolic chemical profiles ofCecropia pachystachyaandCecropia hololeuca

“…These studies have indicated a phenolic‐rich profile, which includes C ‐glycosylated flavonoids, such as orientin, isoorientin, vitexin and isovitexin, in addition to chlorogenic acid. These constituents have been related to biological properties, such as anti‐inflammatory, leishmanicidal, and hypoglycemic activities, among others . Cecropia hololeuca possesses silver leaves, and because of this, is popularly known in Brazil as silver embaúba .…”