Effects of aqueous leaf extracts of Azadirachta indica A. Juss. (neem) and Melia azedarach L. (Santa Barbara or cinnamon) on the intracellular development of Toxoplasma gondii

Abstract

RESUMO: Efeito de extrato aquoso de folhas de Azadirachta indica A. Juss. (nim) e Melia azedarach L. (canela ou Santa Bárbara) sobre o desenvolvimento intracelular de Toxoplasma gondii. Melia azedarach (canela) e Azadirachta indica (nim) apresenta grande variedade de ingredientes biologicamente ativos contra vírus, bactérias e protozoários, mas nenhum efeito sobre o desenvolvimento intracelular do Toxoplasma gondii é conhecido. Toxoplasma gondii infecta todos os tipos de células Eucarióticas, onde se estabelece no meio intracelular em vacúolo modificado conhecido como vacúolo parasitóforo. Neste vacúolo ocorre a replicação levando a ruptura da célula hospedeira e reinfecção de novas células, perpetuando a infecção. A quimioterapia utilizada não é capaz de eliminar o parasita além de induzir fortes efeitos colaterais. Neste estudo, nós demonstramos o efeito in vitro de extratos aquosos da canela e nim sobre o desenvolvimento intracelular do taquizoíto do Toxoplasma gondii. Após tratamento de nim e canela por 24 h, a porcentagem de infecção e o número de taquizoítos intracelulares decaiu drasticamente. Este efeito foi concentração-dependente. Durante incubação dos extratos, uma progressiva desorganização morfológica e ultraestrutural levaram a formação de intensa vesiculação e completa destruição do parasita, que passou a uma estrutura amorfa, antes da completa eliminação do meio intracelular. No entanto durante o tratamento com os extratos, efeitos morfológicos não foram observados nas estruturas da célula hospedeira. Estes resultados sugerem que os extratos aquosos de nim e canela foram capazes de interferir e eliminar o desenvolvimento intracelular do Toxoplasma gondii. Palavras-chave: toxoplasma, nim, canela, citotoxicologiaABSTRACT: Melia azedarach (cinnamon) and Azadirachta indica (neem) have a variety of biologically active ingredients against virus, bacteria and protozoan parasites; however, little is known about their action on Toxoplasma gondii intracellular development. Toxoplasma gondii infects all eukaryotic cells, where it establishes and multiplies inside a modified vacuole called the parasitophorous vacuole until the cell ruptures, re-infecting other cells and establishing the infection. There are no efficient chemotherapies for the elimination of T. gondii, minimizing side effects. In this study, we performed in vitro assays with neem and cinnamon aqueous extracts against the intracellular development of T. gondii tachyzoites. After treatment with neem and cinnamon for 24 h, the percentage of infected cells and the number of intracellular parasites drastically decreased. This effect was concentration-dependent. During the incubation of the extracts, progressive morphological and ultrastructure alterations led to intense vesiculation and complete elimination of the parasite from the intracellular medium. However, during the treatment with extracts, no morphological effects were observed in the structure of the host cell. These results suggest that the aqueous extracts of neem and cinnamon were capa...

Oxidative Stress as a Possible Target in the Treatment of Toxoplasmosis: Perspectives and Ambiguities

“…Moreover, those results confirmed the in vitro antioxidant potential of C. gigantea oil extract, which could be employed for biomedical applications. The beneficial effect on host cells infected with T. gondii was also reported for Eurycoma longifolia root extract [ 113 ] and aqueous extracts of neem and cinnamon leaves [ 114 ]. This effect was associated with antioxidant properties and concomitant anti-Toxoplasma activity of these extracts.…”

A protein extract and a cysteine protease inhibitor enriched fraction from Jatropha curcas seed cake have in vitro anti-Toxoplasma gondii activity

“…3). Similarly, a progressive increase in the concentration of the aqueous extracts of A. indica and M. azedarach leaves did not induce toxicity to host cells, but led to elimination of intracellular tachyzoites (Melo et al, 2011).…”

“…1). The aqueous extracts of Azadirachta indica (neem) and Melia azedarach (cinnamon) leaves altered the intracellular growth of T. gondii, in a dose-dependent way, reducing the infection by 85 and 90%, respectively, at a concentration of 5 mg/mL (Melo et al, 2011). Moreover, a fraction obtained from the root of Zingiber officinale (ginger) inhibited the proliferation of T. gondii without showing toxicity to host cells, probably by inhibiting in these cells the activation of apoptotic proteins induced by parasite proliferation or by inhibition of inflammatory cytokines (Choi et al, 2012).…”

Partially Purified Leaf Fractions of Azadirachta indica Inhibit Trypanosome Alternative Oxidase and Exert Antitrypanosomal Effects on Trypanosoma congolense

“…For example, approximately one quarter of drugs approved for health promotion in the last 2 decades by the Food and Drug Administration and European Medical Agency are from natural products or their derivatives [ 15 , 16 ]. Extracts of Azadirachta indica have demonstrated a broad spectrum anti-protozoan activity against T. evansi [ 17 ], T. brucei rhodesiense [ 18 ], T. cruzi [ 19 ], Leishmania amazonensis [ 20 ], and Toxoplasma gondii [ 21 ]. Here, anti- T. congolense activity of hexane extract of A. indica is evaluated along with its potential to inhibit TAO.…”

“…The ethnopharmacological applications of A. inidica include management of tuberculosis, trypanosomiasis, malaria, cancer, diarrhea, gastric ulcer, wound, and fungal infection [ 22 , 23 ]. Phytochemical constituents such as nimbin, nimbidin, nimbolide, limonoids, 7α-acetyl-15β-methoxy-29 methylene 7,15-deoxo nimbolide, 2-oxo-3-deacetyl salannin, and 7α-hydroxy-15β-hydroxy-7,15-deoxo nimbin have been isolated from the plant [ 21 , 22 ].…”