Traditional medicines have been used to treat malaria for thousands of years and are the source of artemisinin and quinine derivatives. With the increasing levels of drug resistance, the high cost of artemisisnin-based combination therapies, and fake antimalarials drugs, traditional medicine have become an important and sustainable source of malaria treatment. For the benefit of those who use traditional medicine to treat malaria, there is an urgent need to study the efficacy and toxicity of herbal remedies. Hintonia latiflora stem bark infusions are use in Mexican traditional medicine to treat malaria, diabetes, and gastrointestinal diseases. Its efficacy in the treatment of complicated malaria and its ability to generate DNA damage to the host is not fully evaluated. In our search for antimalarial natural products, in the present study, we tested the efficacy of H. latiflora stem bark methanolic extract (HlMeOHe) in CD1 male mice infected with lethal Plasmodium yoelii yoelii and its in vivo cytotoxicity and genotoxicity. To assess the antimalarial activity, the extract was evaluated in a 4-day test scheme in oral doses of 1,200, 600, and 300 mg/kg prior acute toxicity test; oral chloroquine (15 mg/kg) was used as positive control. The ability of 1,200 mg/kg of HlMeOHe to induce cytotoxicity and DNA damage in the peripheral blood of mice was assessed using a fluorochrome-mediated viability test and the micronucleus (MN) assay; N-ethyl-N-nitrosourea (ENU) was used as a positive control. HlMeOHe median acute toxicity (LD₅₀) was 2,783.71 mg/kg and LD10 was 1,293.76 mg/kg (taken as the highest work dose). Plasmodium yoelii yoelii-infected mice in the untreated control group died between 6 and 7 days post-infection (PI) with parasitemia over 70%. Even though mice treated with 600 and 300 mg/kg showed a chemosuppression percentage of total parasitemia of 99.23 and 23.66, respectively, animals in both groups died 6 to 7 days PI with parasitemia over 45%. A 4-day dosage of 1,200 mg/kg of the extract showed, in the P. yoelii yoelii-infected mice, a 100% chemosuppression of total parasitemia on 5 days PI and a 23 days survival time with a mean parasitemia of 23.6% at the date of death. Only mice treated with chloroquine survived until the end of the experiment. Cell viability was not affected. The average number of micronuclei in the treated mice increased significantly (P < 0.05) to 4.8 MN when compared with the untreated control group (0.9 MN). The results obtained in this study showed that the infection outcome of P. yoelii yoelii-infected mice is affected by HlMeOHe. Although a concentration of 1,200 mg/kg of HlMeOHe is suitable to use in the treatment of malaria fever, slowed down the parasite replication, retarded the patency time, and increased the infected P. yoelii yoelii mice survival time, its chemical composition should be studied in detail in order to reduce its genotoxic potential.
The compound VAM2-6 (1-methyl-7-nitro-4-(5-(piperidin-1-yl)pentyl)-3,4-dihydroquinoxalin-2(1H)-one) has previously been shown to have an in vitro efficacy of 100% at a concentration of 100 µg ml(-1) against Trichomonas vaginalis, a protozoon parasite that causes the sexually transmitted disease trichomoniasis. Because VAM2-6 is a quinoxaline derivative and given the lack of studies on the genotoxic activity of this compound, the present study was undertaken to evaluate its ability to induce DNA damage in the peripheral blood of mice using single-cell gel electrophoresis (SCGE or comet assay) and the micronucleus (MN) assay. Cell viability was assessed using a fluorochrome-mediated viability test. The compound was tested on CD1 mice at 60, 40 and 10 mg kg(-1) body weight administrated intraperitoneal (i.p.) in a single dose. Peripheral blood samples were collected 24 and 48 h after treatment. N-Ethyl-N-nitrosourea (ENU) was used as a positive control for the comet and micronucleus assays. The results showed that i.p. VAM2-6 induced single-strand DNA breaks and increased the average number of micronuclei in the treated mice in a dose-dependent manner at 60, 40 and 10 mg kg(-1). Cell viability decreased at 24 h but recovered at 48 h for all three evaluated doses. Therefore, the chemical structure of VAM2-6 should be modified to reduce its genotoxic potential.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.
Copyright © 2025 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.