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Background: Community consumption of herbal plants in developing countries is a common practice, however, scarcity of information on their physiochemical composition is a major public health concern. In Uganda, Vernonia amygdalina is of interest in rural communities due to its therapeutical action on both bacterial and protozoal parasites, however no studies have been conducted to assess the heavy metal concentrations in traditional plants used in alternative medicine. The aim of the study was to establish concentrations of heavy metals in Vernonia amygdalina, model the estimated daily intake (EDI), and assess both the non-cancer-related health risk using the target hazard quotient (THQ), and the risk related to cancer through the incremental lifetime cancer risk (ILCR) for the Ugandan population. Methods: Leaves of Vernonia amygdalina were collected from 20 georeferenced villages and processed into powder in the laboratory using standard methods. These were then analyzed in the laboratory using an atomic absorption spectrometer for lead (Pb), chromium (Cr), copper (Cu), zinc (Zn), cobalt (Co), iron (Fe), cadmium (Cd), and nickel (Ni). Concentrations were compared against the World Health Organization (WHO) limits. The EDI, THQ, and ILCR were modelled and significance was measured at 95% confidence. Results: The study showed that mean ± SEM concentrations of heavy metals were highest in the order of Cr, 121.8 ± 4.291 ppm > Ni, 84.09 ± 2.725 ppm > Zn, 53.87 ± 2.277 ppm > Pb, 40.61 ± 3.891 ppm > Cu, 28.75 ± 2.202 ppm > Fe, 14.15 ± 0.7271 ppm > Co, 7.923 ± 0.7674 ppm > Cd, 0.1163 ± 0.005714 ppm. Concentrations of Pb, Cr, Zn, Co, and Ni were significantly higher than the WHO limits. The EDI was significantly higher in children than in adults, demonstrating an increased risk of toxicity in children. The THQ and ILCR were over 1000 times higher in all Ugandans, demonstrating the undesirable health risks following oral consumption of Vernonia amygdalina due to very high Cr and Ni toxicities, respectively. Conclusion: Consumption of raw Vernonia amygdalina was associated with a high carcinogenic risk, demonstrating a need to enact policies to promote physiochemical screening of herbal medicines used in developing countries against toxic compounds.

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OBJECTIVE: This study investigated the acute and subacute toxicity of whole-plant aqueous extract of Vernonia mespilifolia Less. (AEVM) in rats for evaluating its safety profile. METHODS: AEVM for the acute (2000 and 5000 mg/kg) and subacute (200, 400 and 600 mg/kg) toxicity studies was administered orally to rats according the guidelines 425 and 407 of Organization for Economic Cooperation and Development, respectively. Food and water intake as well as body and organ weight of animals were recorded. Signs of toxicity were assessed, and hematological, biochemical and histopathological analyses were performed. RESULTS: In the acute toxicity study, a single dose of the aqueous extract at 2000 or 5000 mg/kg caused no mortality in the animals, suggesting that the median lethal dose is greater than 5000 mg/kg. In the subacute toxicity study, administration of the extract for 28 d, at all doses, caused no significant changes in the body weights or organ weights of rats in the treated groups when compared with the control group. In addition, hematological and biochemical parameters also revealed no toxic effects of the extract on rats. Histological sections of the heart, liver and kidney from test animals showed no signs of degeneration. CONCLUSION: These results showed that AEVM at dosage levels up to 600 mg/kg is nontoxic and could also offer protection on some body tissues. AEVM could, therefore, be considered safe.

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Despite the widespread use of Vernonia anthelmintica seeds in traditional medicine, the need to establish the safety of the Vernonia anthelmintica is required to ascertain the safe use of this herbal medicine. The aim of the present study is to establish the acute toxicity profile of different extracts of Vernonia anthelmintica. Hexane and ethanol extract of Vernonia Anthelmintica has been studied for its brine shrimp lethality potential. Water decoction (WDVA), Hexane (HEVA) and Ethanol (EEVA) extracts of Vernonia anthelmintica has also been evaluated for their in-vivo acute oral toxicity in mice by Lorke's method. Phytochemistry of all three extracts was also evaluated for the presence of their secondary metabolites. All three extracts showed the presence of flavonoids and terpenoids, while alkaloids, tannins and fixed oils were present in HEVA and EEVA. Furthermore EEVA also showed presence of carbohydrates and HEVA also showed the presence of cardiac glycosides. Ethanol and hexane extracts of Vernonia anthelmintica showed a positive cytotoxicity in brine shrimp lethality test at 24 hours with LC50 104.16 (224.0-48.05)µg/ml and 216.11µg/ml (378.2-128.7) respectively as compared to standard drug etoposide LC50 7.46µg/ml. The oral LD50 for EEVA, HEVA and WDVA in mice by Lorke's method was greater than 5000mg/kg. The result of brine shrimp lethality test clearly exhibited the presence of bioactive compounds with cytotoxic potential; however seems to be safe for oral use since LD50 was higher than 5000mg/kg and thus safety of acute dosing in vivo practices is justified.

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Vernonia amygdalina (bitter-leaf) is native to West Africa but occurs mostly in its cultivated form in various parts of central and southern Nigeria. It is a dark-green leafy vegetable commonly used in cooking and as folkloric medicine for the management of several diseases in Nigeria. In the present study, the effects of varying doses of ethanolic leaf extract of Vernonia amygdalina on the rat testis histo-morphometry were investigated. Forty male wistar rats were divided into groups of four. Group A, as the control was given 10 ml/kg/day/oral distilled water while Group B, C and D subsequently treated with 100, 300 and 600 mg/kg/day/oral route Vernonia amygdalina leaves extract respectively for 56 days. Results showed that Group B rats had normal testis histology comparable to the control group. However, rats in Group C and D exhibited dose-dependent poor testes histo-morphometric profiles, with the higher dosage-group (D) providing a worse feature. Thus, there was a statistically significant (p < 0.05) reduction in the tubular diameter, cross-sectional area of the tubules, number of tubular profiles per unit area and the mean numerical density of seminiferous tubules of Group C and Group D animals compared to the control group. Our results therefore indicated that, while the lower dose (100 mg/kg) of Vernonia amygdalina leaves extract can be accommodated by rat testis, the higher doses (300 mg/kg and 600 mg/kg) demonstrate testicular toxicity in the rat.

La Vernonia amygdalina (hoja amarga) es originaria de África Occidental, pero se produce mediante cultivo en varias partes del Centro y Sur de Nigeria. Es una verdura, una hoja color verde oscuro, común en la cocina y como medicina alternativa en el manejo de varias enfermedades en Nigeria. Se investigaron los efectos de diferentes dosis de extracto etanólico de la hoja de Vernonia amygdalina para estudiar los efectos sobre la histomorfometría testicular en la rata. Cuarenta ratas Wistar macho se dividieron en 4 grupos. Grupo A, como control con el suministro de 10 ml/kg/día/agua destilada vía oral, y los Grupos B, C y D tratados con 100, 300 y 600 mg/kg/día/ vía oral del extracto de Vernonia amygdalina, durante 56 días. Los resultados mostraron que las ratas del grupo B tenían una histología testicular normal y comparable con el grupo control. Sin embargo, las ratas del grupo C y D mostraron bajos perfiles histomorfométricos testiculares, dependientes de la dosis, y con la dosis más elevada, grupo (D) se observaron característica aún menores. Hubo una reducción estadísticamente significativa (p<0,05) en el diámetro tubular, área de sección transversal de los túbulos, número túbulos por unidad de superficie y densidad numérica media de los túbulos seminíferos del Grupo C y D en comparación con el grupo de control. Nuestros resultados indicaron que dosis bajas (100 mg/kg) del extracto de Vernonia amygdalina pueden ser aceptables y no alteran el testículo de rata, pero con dosis altas (300 mg/kg y 600 mg/kg) se observa toxicidad testicular.

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ETHNOPHARMACOLOGICAL RELEVANCE: The Vernonia genus has about one thousand species and members of the genus are widely used as food and medicine. The aim of this review is to analyze published data on the ethnomedicinal, ethnoveterinary and zoopharmacognostic uses of plants of the Vernonia genus. This will help to identify the state of ethnopharmacological knowledge in regard to this genus and to propose future research priorities. MATERIALS AND METHODS: The major scientific databases including SciFinder, Sciencedirect, Medline and Google Scholar were queried for information on Vernonia genus using various keyword combinations. The International Plant Name Index was also used to verify the names of species and authors. RESULTS: A total of 109 Vernonia species were reported in the literature to have medicinal properties. One hundred and five (105) plants were linked to the treatment or management of 44 human diseases or health conditions. Plants of the genus also feature in ethnoveterinary and zoopharmacognostic practices. A total of 12 vernonia species were identified to be used in ethnoveterinary medicine while 2 species are used in self medication practices by chimpanzees and gorillas. In vitro and in vivo research studies reporting the validation of the medicinal properties of some species were also reviewed. One hundred and three bioactive compounds isolated from various Vernonia species were also identified. Vernonia amygdalina was identified as the most frequently used member of the Vernonia genus. The Vernolides, a class of sesquiterpene lactone were identified as the most studied compounds from the genus and show interesting bioactivity in antiplasmodial, antileishmanial, antischistosomial, cytotoxicity, antimicrobial and anti-inflammatory assays. CONCLUSION: On the basis of results from a combination of in vitro and in vivo efficacy and toxicity studies reported, Vernonia amygdalina holds the most promise for development into a nutraceutical against diabetes and malaria while Vernonia cinerea has potential against cancer and inflammatory conditions. Vernolide A is so far the most promising single agent from a Vernonia species that has potential for development into an anticancer agent. The other Vernonia species and isolated compounds require further studies to ascertain their medicinal potentials.

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Extract of Vernonia condensata (Asteraceae = Compositae) leaves has different uses in Brazilian folk medicine, which includes analgesic and antiinflamatory agent. The aim of this study was to apply a modified simplex-centroid mixture design to evaluate the best extractor system for the antinociceptive activity, evaluated by writhing test. Different solvents (acetone, dichloromethane, ethanol and ethyl acetate) as well as their binary, ternary and quaternary mixtures were used. For comparison, aqueous extract was also evaluated. LD50 was estimated and qualitative phytochemical screening, conducted. The extracts with antinociceptive activity were: aqueous, acetone, dicloromethane (DCM), ethanol (ETOH), acetone-DCM, acetone-ETOH, acetone-ethyl acetate, ETOH-ethyl acetate, acetone-DCM-ethyl acetate, acetone-ETOH-ethyl acetate and DCM-ETOH-ethyl acetate. The higher margin of safety (LD50/ED50) was for acetone > acetone-ETOH-ethyl acetate > aqueous > ETOH = acetone-ETOH > DCM > acetone-ethyl acetate > DCM-ETOH-ethyl acetate > acetone-DCM > acetone-DCM-ethyl acetate. Phytochemical screening showed that all the extracts contained alkaloids, phenolic compounds, flavonoids, tannins and saponins. In conclusion, the extractor system influences both the pharmacological activity and acute toxicity of leaves from V. condensata. Acetone and the ternary mixture, acetone-ETOH-ethyl acetate extracts showed higher margin of safety than aqueous extract.

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Vernonia amygdalina possesses several bioactive compounds and is used in traditional medicines of southwestern Uganda, along with other regions. Its analgesic potential has not been investigated thus far. The present study examines the antinociceptive potential of the aqueous leaf extract (50-200 mg/kg) using three models of nociception (acetic acid-induced writhing, formalin test, and tail-flick test), antiplasmodial activity, and toxicology of the extract. The results show the extract significantly inhibits acetic acid-induced writhing and the formalin test in mice but did not give a potent effect in the tail-flick test, suggesting that the extract may have peripheral and central analgesic properties. The extract also exhibited significant antiplasmodial activity in mice against Plasmodium berghei with 73% inhibition in the group that received a dose of 200 mg/kg i.p. daily for 4 days. Toxicology results show no clinical signs of toxicity or adverse toxicological effects in the treated groups, except for a significant decrease in red blood cell count and a dose-dependent increase in serum bilirubin. These changes were within control values based on historical reference ranges at doses of 500-2,000 mg/kg/day for 14 consecutive days as compared to the control. This study supports the traditional use of V. amygdalina as an alternative therapy for malaria and the symptomatic relief of pain usually associated with malaria.

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