Activity of the genus Zanthoxylum against diseases caused by protozoa: A systematic review

Abstract

Neglected diseases (NDs) are treated with a less varied range of drugs, with high cost and toxicity, which makes the search for therapeutic alternatives important. In this context, plants, such as those from the genus Zanthoxylum, can be promising due to active substances in their composition. This study evaluates the potential of species from this genus to treat NDs. Initially, a protocol was developed to carry out a systematic review approved by Prospero (CRD42020200438). The databases PubMed, BVS, Scopus, Science Direct, and Web of Science were used with the following keywords: “zanthoxylum,” “xanthoxylums,” “fagaras,” “leishmaniasis,” “chagas disease,” “malaria,” and “African trypanosomiasis.” Two independent evaluators analyzed the title and abstract of 166 articles, and 122 were excluded due to duplicity or for not meeting the inclusion criteria. From the 44 selected articles, results of in vitro/in vivo tests were extracted. In vitro studies showed that Z. rhoifolium, through the alkaloid nitidine, was active against Plasmodium (IC50 <1 μg/ml) and Leishmania (IC50 <8 μg/ml), and selective for both (>10 and >30, respectively). For Chagas disease, the promising species (IC50 <2 μg/ml) were Z. naranjillo and Z. minutiflorum, and for sleeping sickness, the species Z. zanthoxyloides (IC50 <4 μg/ml) stood out. In the in vivo analysis, the most promising species were Z. rhoifolium and Z. chiloperone. In summary, the species Z. rhoifolium, Z. naranjillo, Z. minutiflorum, Z. zanthoxyloides, and Z. chiloperone are promising sources of active molecules for the treatment of NDs.

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

“…Several biological activities of extracts from Z. rhoifolium have been described, such as action against promastigotes and amastigotes [ 13 ], an inhibitory effect on macrophage infection in Leishmania amazonensis [ 14 ], activity against intestinal nematodes [ 15 ], and antibacterial [ 7 , 16 ], antifungal [ 17 ], antiplasmodial [ 18 ], and antitumor activities [ 19 ]. Moreover, several of these activities have been attributed to alkaloids including antiviral action [ 20 ] and neuromuscular blockade [ 21 ].…”

“…There have been numerous chemical studies of Z. rhoifolium isolated alkaloids (Figure 1) with a benzophenanthridine nucleus: bocconoline (1), chelerythrine (2), 6acetonyldihydrochelerythrine (3), zanthoxyline (4), rhoifoline A (5), rhoifoline B (6), fagaramide (7), avicine (8), oxyavicine (9), nitidine (10), and oxynitidine (11), and those with a furoquinoline nucleus: skimmianine ( 12) and E-Z-dimethylroifolinate (13) [5][6][7][8][9][10][11][12]. Several biological activities of extracts from Z. rhoifolium have been described, such as action against promastigotes and amastigotes [13], an inhibitory effect on macrophage infection in Leishmania amazonensis [14], activity against intestinal nematodes [15], and antibacterial [7,16], antifungal [17], antiplasmodial [18], and antitumor activities [19]. Moreover, several of these activities have been attributed to alkaloids including antiviral action [20] and neuromuscular blockade [21].…”

“…The in silico prediction of the toxicity of compounds allows us to choose among the available components those which will progress to future phases of analysis, thus utilizing mathematical methods that, when based on structure-property models, allow a reduction in expenses and avoid the unnecessary use of animals [26]. Several biological activities of extracts from Z. rhoifolium have been described, such as action against promastigotes and amastigotes [13], an inhibitory effect on macrophage infection in Leishmania amazonensis [14], activity against intestinal nematodes [15], and antibacterial [7,16], antifungal [17], antiplasmodial [18], and antitumor activities [19]. Moreover, several of these activities have been attributed to alkaloids including antiviral action [20] and neuromuscular blockade [21].…”