A importância medicinal de Zanthoxylum rhoifolium Lam. (Rutaceae)

Chagas, Cristian Kallahan Silva; Corrêa-Barbosa, Juliana; Sodré, Daniele Ferreira; Nascimento, Pedro; Brígido, Heliton Patrick Cordovil; Mota, Tatiane Cristina; Bahia, Marcelo de Oliveira; Dolabela, Maria Fâni

doi:10.37423/200802571

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“…Another study demonstrated that fractionation contributed significantly to the reduction in cytotoxicity in normal gastric cells, since the EEZR was more toxic (IC 50 = 77.08 µg/mL), the FAZR was moderately cytotoxic (IC 50 = 127.5 µg/mL), and the FNZR, and a possible alkaloid, were not cytotoxic (IC 50 > 500 µg/mL) [24]. In summary the neutral fraction and alkaloid fraction showed a low cytotoxicity in normal gastric cells, but there is a lack of toxicity studies on this species in the literature, what reinforces the importance of this study.…”

Section: Discussionmentioning

confidence: 99%

“…A preliminary toxicity assessment has already been carried out with an ethanolic extract of Z. rhoifolium against Artemia salina, showing a potential toxic effect for this species [23]. Another study demonstrated that fractionation significantly contributed to the reduction in cytotoxicity in normal gastric cells, since the EEZR was more cytotoxic and the FAZR was moderately cytotoxic, whereas the FNZR, and a possible alkaloid, were not cytotoxic [24]. It is noteworthy that cytotoxicity is not yet well understood as a response to genotoxic agents, because responses to genotoxic damage are complex and can range from repair, damage fixation, mutations, damage deletions, and cell death [25].…”

Section: Introductionmentioning

confidence: 99%

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Cytotoxicity and Genotoxicity Evaluation of Zanthoxylum rhoifolium Lam and In Silico Studies of Its Alkaloids

et al. 2023

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The alkaloids isolated from Zanthoxylum rhoifolium have demonstrated great pharmacological potential; however, the toxic profiles of these extracts and fractions are still not well elucidated. This study evaluated the toxicity of the ethanol extract (EEZR) and neutral (FNZR) and alkaloid (FAZR) fractions. Chemical characterization was performed by chromatographic methods: thin-layer chromatography (TLC) and high-performance liquid chromatography coupled with diode array detection (HPLC–DAD). The cytotoxicity of the samples was evaluated in human hepatocellular carcinoma (HepG2) cells using the cell viability method (MTT) and mutagenicity by the Allium cepa assay (ACA). Alkaloids isolated from the species were selected for toxicity prediction using preADMET and PROTOX. The molecular docking of the topoisomerase II protein (TOPOII) was used to investigate the mechanism of cell damage. In the EEZR, FNZR, and FAZR, the presence of alkaloids was detected in TCL and HPLC–DAD analyses. These samples showed a 50% inhibitory concentration (IC50) greater than 400 μg/mL in HepG2 cells. In ACA, time- and concentration-dependent changes were observed, with a significant reduction in the mitotic index and an increase in chromosomal aberrations for all samples. Nuclear sprouts and a micronucleus of the positive control (PC) were observed at 10 µg/mL and in the FAZR at 30 µg/mL; a chromosomal bridge in FNZR was observed at 105 µg/mL, CP at a concentration of 40 µg/mL, and nuclear bud and mitotic abnormalities in the EEZR were observed at 170 µg/mL. The alkaloids with a benzophenanthridine were selected for the in silico study, as structural alterations demonstrated certain toxic effects. Molecular docking with topo II demonstrated that all alkaloids bind to the protein. In summary, the fractionation of Z. rhoifolium did not interfere with toxicity; it seems that alkaloids with a benzophenanthridine nucleus may be involved in this toxicity.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%