RESUMEN
ETHNOPHARMACOLOGY RELEVANCE: Palm buds are a natural green resource of the forest, which are not only rich in nutrients but contain a large number of phenolic acids and flavonoids, among other components. It has a variety of biological activities such as antioxidant and uterine smooth muscle stimulation. AIM OF THE STUDY: To evaluate the safety of palm buds for use as a nutraceutical product and food by evaluating the toxicity, subacute toxicity and genotoxicity of the young palm buds. Also studied for its immune-enhancing activity. MATERIALS AND METHODS: Acute toxicity tests were performed in mice using the maximum tolerance method, and the manifestations of toxicity and deaths were recorded after administration of 10,000 mg/mL for 14 consecutive d (days) of observations. To assess subacute toxicity, mice were treated with palm buds (750, 1500, or 3000 mg/mL) daily for 28 days. The teratogenicity of palm buds was assessed by the Ames test, the mouse bone marrow cell micronucleus test, and the mouse spermatozoa malformation test. In addition, we evaluated the immune-enhancing ability of palm buds by the mouse carbon profile test, delayed-type metamorphosis reaction, and serum hemolysin assay. RESULTS: In the acute toxicity study, the Median Lethal Dose (LD50) was greater than 10,000 mg/kg bw in both male and female rats. There were also no deaths or serious toxicities in the subacute study. The no-observed-adverse-effect level (NOAEL) was 3000 mg/kg bw. However, the mice's food intake decreased after one week. The medium and high dose groups had a reducing effect on body weight in mice of both sexes. In addition, the changes in organ coefficients of the liver, kidney and stomach in male mice were significantly higher in the high-dose group (3.23 ± 0.35, 0.75 ± 0.05, 0.57 ± 0.05 g) than in the control group (2.94 ± 0.18, 0.58 ± 0.05, 0.50 ± 0.02 g). Hematological analyses showed that all the indices of the rats in each palm sprout dose group were within the normal range. The results of blood biochemical indicators showed that there was a significant reduction in TP in the blood of male mice in the high-dose group (44.6 ± 7.8 g/L) compared to the control group (58.3 ± 15.1 g/L). In histopathological analysis, none of the significant histopathological changes were observed. The results of the immunological experiment in mice showed that the liver coefficient and thymus coefficient of the high-dose group (8400 mg/kg) were significantly lower than the control group. There was no remarkable difference in auricle swelling between each dose palm bud group (1400, 2800, or 8400 mg/kg) and the control group. The anti-volume number of the high-dose group was significantly increased. CONCLUSION: Palm buds have non-toxic effects in vivo and have little effect on non-specific and cellular immunity in the test mice within the dose range of this experiment. The immunoenhancement in mice is mainly achieved through humoral immunity. In conclusion, our results suggest that palm buds are safe for use as healthcare products and food.
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Arecaceae , Pruebas de Toxicidad Aguda , Animales , Femenino , Masculino , Arecaceae/química , Ratones , Extractos Vegetales/toxicidad , Extractos Vegetales/farmacología , Extractos Vegetales/administración & dosificación , Factores Inmunológicos/toxicidad , Ratas , Pruebas de Toxicidad Subaguda , Relación Dosis-Respuesta a Droga , Pruebas de Micronúcleos , Pruebas de Mutagenicidad , Proteínas Hemolisinas/toxicidad , Dosificación Letal MedianaRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: The popularity of herbal medicine is expanding globally due to the common belief that herbal products are natural and nontoxic. Thymelaea hirsuta leaves are traditionally used for the treatment of recurrent abortion in humans and animals. However, a lack of safety evaluation of the plant, particularly in pregnant women, raises serious concerns regarding its potential embryotoxic effects. AIM OF THE STUDY: Therefore, the present study investigated the safety of Thymelaea hirsuta leaves aqueous extract (THLE) during pregnancy and lactation following maternal rat treatment. MATERIALS AND METHODS: THLE phytochemical compounds were identified using high-performance liquid chromatography (HPLC). THLE was orally administered to pregnant rats and lactating dams at dosages of 0, 250, 500, and 1000 mg/kg/day. At the end of the study, dam s' and pups' body weights, serum biochemical and hematological indices, and histopathological changes were investigated. For the fetal observation and histopathological changes were also evaluated. RESULTS: Our findings revealed that THLE is rich in different phenolic and flavonoid compounds. However, biochemical and hormonal parameters such as ALT, AST, and prolactin were significantly increased in dams treated with a higher dosage of THLE when compared to the control dams (P ≤ 0.05). Additionally, external, visceral and skeletal examinations of fetuses revealed a marked increase of malformation rates in treated fetuses. CONCLUSIONS: The results revealed that higher oral dosing of THLE during pregnancy could affect embryonic development in rats, while lower doses are safe and can be used during pregnancy and lactation to attain its beneficial effects.
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Extractos Vegetales , Hojas de la Planta , Ratas Wistar , Thymelaeaceae , Animales , Extractos Vegetales/toxicidad , Extractos Vegetales/farmacología , Femenino , Embarazo , Ratas , Thymelaeaceae/química , Lactancia , Reproducción/efectos de los fármacos , Masculino , Relación Dosis-Respuesta a DrogaRESUMEN
Coal plays a crucial role in Indonesia's foreign exchange and East Kalimantan's revenue sharing, yet its environmental impacts, including soil acidification, raises concerns. Reclamation measures involve revegetation with pioneer plants such as Macaranga sp., known for their medicinal properties. However, the pharmacological properties of these plants are influenced by secondary metabolites, which depend on soil parameters such as pH and nutrient levels. The aim of this study was to evaluate the acute toxicity, secondary metabolites, and antioxidant activities of Macaranga tanarius leaf extracts from post-coal mining area (MTPCMA) and non-mining area (MTNMA) alongside soil parameters. Acute toxicity of M. tanarius leaf extracts and soils were assessed using the brine shrimp lethality test (BSLT). Phytochemical screening was done using thin-layer chromatography (TLC), determining total phenolic (TPC) and flavonoid content (TFC). The DPPH radical scavenging assay was used to assess the antioxidant activity. A comparative analysis between MTPCMA and MTNMA was conducted using Student t-test. The data showed no significant difference in toxicity between MTPCMA and MTNMA leaf extracts (LC50 of 100-1000 µg/mL) (p=0.062), and soils from both areas were non-toxic (LC50 of >1000 µg/mL). Although heavy metal concentrations were higher in PCMA than in NMA soil (p<0.001), secondary metabolite compounds and TFC in both extracts were not significantly different (p=0.076). Both extracts contained flavonoids and polyphenols with antioxidant activity and terpenoids without antioxidant activities. The DPPH radical scavenging test suggested insignificant antioxidant activity between MTPCMA and MTNMA extracts (p=0.237). In conclusion, non-toxic soils in post-mining land and insignificant differences between MTPCMA and MTNMA extracts suggest good soil nutrient availability, highlighting the success of land recovery after 10 years of revegetation with M. tanarius.
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Antioxidantes , Artemia , Extractos Vegetales , Indonesia , Antioxidantes/metabolismo , Animales , Extractos Vegetales/química , Extractos Vegetales/toxicidad , Extractos Vegetales/farmacología , Artemia/efectos de los fármacos , Hojas de la Planta/química , Minas de Carbón , Suelo/química , Pruebas de Toxicidad Aguda , Fitoquímicos/análisis , Fitoquímicos/toxicidad , Flavonoides/análisis , Flavonoides/metabolismo , Metabolismo SecundarioRESUMEN
Humans have been using plants in the treatment of various diseases for millennia. Currently, even with allopathic medicines available, numerous populations globally still use plants for therapeutic purposes. Although plants constitute a safer alternative compared to synthetic agents, it is well established that medicinal plants might also exert adverse effects. Thus, the present investigation aimed to assess the phytotoxic, cytotoxic, and genotoxic potential of two plants from the Brazilian Cerrado used in popular medicine, Davilla nitida (Vahl) Kubitzki, and Davilla elliptica (A. St.-Hil.). To this end, germination, growth, and cell cycle analyses were conducted using the plant model Lactuca sativa. Seeds and roots were treated with 0.0625 to 1 g/L for 48 hr under controlled conditions. The germination test demonstrated significant phytotoxic effects for both species at the highest concentrations tested, while none of the extracts produced significant effects in the lettuce growth test. In the microscopic analyses, the aneugenic and cytotoxic action of D. elliptica was evident. In the case of D. nitida greater clastogenic action and induction of micronuclei, (MN) were noted suggesting that the damage initiated by exposure to these extracts was not repaired or led to apoptosis. These findings indicated that the observed plant damage was transmitted to the next generation of cells by way of MN. These differences in the action of the two species may not be attributed to qualitative variations in the composition of the extracts as both are similar, but to quantitative differences associated with synergistic and antagonistic interactions between the compounds present in these extracts.
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Dilleniaceae , Lactuca , Extractos Vegetales , Plantas Medicinales , Plantas Medicinales/toxicidad , Plantas Medicinales/química , Extractos Vegetales/toxicidad , Lactuca/efectos de los fármacos , Lactuca/crecimiento & desarrollo , Dilleniaceae/química , Germinación/efectos de los fármacos , Semillas/efectos de los fármacos , Brasil , Ciclo Celular/efectos de los fármacos , Raíces de Plantas/efectos de los fármacosRESUMEN
Olive mill wastewater (OMWW), with its high level of phenolic compounds, simultaneously represents a serious environmental challenge and a great resource with potential nutraceutical activities. To increase the knowledge of OMWW's biological effects, with an aim to developing a food supplement, we performed a chemical characterisation of the extract using the Liquid Chromatography-Quadrupole Time-of-flight spectrometry (LC-QTOF) and an in vitro genotoxicity/antigenotoxicity assessment on HepaRG ™ cells. Chemical analysis revealed that the most abundant phenolic compound was hydroxytyrosol. Biological tests showed that the extract was not cytotoxic at the lowest tested concentrations (from 0.25 to 2.5 mg/mL), unlike the highest concentrations (from 5 to 20 mg/mL). Regarding genotoxic activity, when tested at non-cytotoxic concentrations, the extract did not display any effect. Additionally, the lowest tested OMWW concentrations showed antigenotoxic activity (J-shaped dose-response effect) against a known mutagenic substance, reducing the extent of DNA damage in the co-exposure treatment. The antigenotoxic effect was also obtained in the post-exposure procedure, although only at the extract concentrations of 0.015625 and 0.03125 mg/mL. This behaviour was not confirmed in the pre-exposure protocol. In conclusion, the present study established a maximum non-toxic OMWW extract dose for the HepaRG cell model, smoothing the path for future research.
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Daño del ADN , Olea , Aguas Residuales , Aguas Residuales/toxicidad , Aguas Residuales/química , Humanos , Olea/química , Daño del ADN/efectos de los fármacos , Línea Celular , Extractos Vegetales/toxicidad , Extractos Vegetales/química , Pruebas de Mutagenicidad , Fenoles/toxicidad , Fenoles/análisis , Mutágenos/toxicidadRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Abutilon indicum, a shrub of the Malvaceae family, is found abundantly in tropical countries like India. A. indicum is widely used for its high medicinal properties. Traditionally, A. indicum seed powder is consumed to treat piles, constipation, chronic cystitis, gonorrhea, gleet, and pregnancy-related problems. Despite having numerous medicinal properties and widespread traditional use of A. indicum seeds, scientific validation, and toxicity studies have yet to be documented. AIMS OF THE STUDY: The primary objective of this study is to conduct a comprehensive study on phytochemical profiling, in-vitro cytotoxicity, mutagenicity, and in-vivo acute and sub-acute toxicity, and genotoxicity on animal models of methanolic extract of A. indicum seed (MAS). MATERIALS AND METHODS: The qualitative analysis of MAS was explored through FTIR and HR LC-MS. For in-vitro cytotoxicity, the HEK-293 cell line was used, and the TA100 (Staphylococcus typhimurium) bacterial strain was used for the Ames mutagenicity test. A single oral dose of 250, 500, 1000, or 2000 mg/kg body weight of MAS was given to each male and female rat for acute toxicity study and observed for 14 days for any toxicity signs. In the sub-acute toxicity study, 250, 500, or 1000 mg/kg body weight of MAS was administered orally to each rat for 28 days. The experimental animals were weighed weekly, and general behavior was monitored regularly. After 28 days of the experiment, the rats were sacrificed, and different serum biochemical, hematological, and histological analyses were performed. The blood samples of different doses of MAS were used for genotoxicity study through comet assay. RESULTS: FTIR analysis found different functional groups, which indicated the presence of phenolics, flavonoids, and alkaloids. HR LC-MS analysis depicts several components with different biological functions. The cell cytotoxicity and Ames mutagenicity results showed minimal toxicity and mutagenicity up to a certain dose. The acute toxicity study conducted in Wistar albino rats demonstrated zero mortality among the animals, and the LD50 value for seed extract was determined to be 2000 mg/kg body weight. Sub-acute toxicity assessments indicated that the administration of seed extract resulted in no adverse effects at dosages of 250 and 500 mg/kg body weight. However, at higher doses, specifically 1000 mg/kg body weight, the liver of the experimental rats exhibited some toxic effects. In the genotoxicity study, minimal DNA damage was found in 250 and 500 mg/kg doses, respectively, but slightly greater DNA damage was found in 1000 mg/kg doses in both male and female rats. CONCLUSIONS: The consumption of A. indicum seed powder is deemed safe; however, doses exceeding 500 mg/kg body weight may raise concerns regarding use. These findings pave the path for the creation of innovative medicines with improved efficacy and safety profiles.
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Malvaceae , Pruebas de Mutagenicidad , Extractos Vegetales , Semillas , Animales , Extractos Vegetales/toxicidad , Extractos Vegetales/administración & dosificación , Femenino , Semillas/química , Masculino , Humanos , Ratas , Células HEK293 , Malvaceae/química , Salmonella typhimurium/efectos de los fármacos , Salmonella typhimurium/genética , Metanol/química , Pruebas de Toxicidad Aguda , Relación Dosis-Respuesta a Droga , Supervivencia Celular/efectos de los fármacos , Ratas Wistar , Ratas Sprague-DawleyRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Moringa oleifera (Moringaceae family), commonly known as horseradish or tree of life, is traditionally used for various diseases, such as diabetes, hypercholesterolemia, neurological disorders, among others. AIM OF THE STUDY: To evaluate the toxicological profile of the oral use of an aqueous extract of Moringa oleifera leaves for 13 weeks in mice. MATERIALS AND METHODS: Initially, a factorial design (23) was carried out to optimize aqueous extraction using as variables; the extraction method and proportion of drug. The 13-week repeated-dose toxicity trial used female and male mice, with oral administration of aqueous extract of Moringa oleifera leaves at doses of 250, 500, and 1000 mg/kg. The animals were evaluated for body weight, water and feed intake, biochemical and hematological parameters, urinalysis, ophthalmology and histopathology of the liver, spleen and kidneys. RESULTS: The extraction efficiency was evidenced by the extraction by maceration at 5%, obtaining the optimized extract of Moringa oleifera (OEMo). The oral administration of OEMo did not promote significant difference (p > 0.05) in the weight gain, food and water consumption of the control animals and those treated with 250 and 500 mg/kg. However, treatment with 1000 mg/kg promoted a reduction (p < 0.05) in food intake and body weight from the 7th week onwards in male and female mice. No alterations were detected in the hematological and histological parameters in the concentrations tested for both sexes. The highest concentration treatment (1000 mg/kg) promoted an increase in transaminases in males and females. All concentrations promoted a significant decrease (p < 0.05) in the serum lipid profile of mice. CONCLUSION: This study developed an optimized extract of Moringa oleifera leaves, which should be used with caution in preparations above 500 mg/kg for the long term because it leads to significant changes in liver enzymes. On the other hand, the extract proved to be a promising plant preparation for hyperlipidemia in mice.
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Moringa oleifera , Extractos Vegetales , Hojas de la Planta , Animales , Moringa oleifera/química , Extractos Vegetales/toxicidad , Extractos Vegetales/administración & dosificación , Extractos Vegetales/farmacología , Masculino , Femenino , Ratones , Peso Corporal/efectos de los fármacos , Ingestión de Alimentos/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Hígado/efectos de los fármacos , Hígado/patología , Administración Oral , Riñón/efectos de los fármacos , Riñón/patologíaRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Valeriana officinalis L., commonly known as "valerian", is a traditional herbal medicine distributed in the north temperate zones of America, Europe and Asia. In traditional Chinese medicine, valerian and its roots were used for the treatment of restlessness of the heart and mind, palpitation and insomnia caused by internal depression of emotions and moods. However, safety evaluation of valerian remains deeply unclear. AIM OF THE STUDY: This study aimed to evaluate the genotoxicity, 14-days acute oral toxicity test, 90-day subchronic oral toxicity test and teratogenicity test of aqueous extract of valerian root (AEVR). MATERIALS AND METHODS: The genotoxicity of AEVR was evaluated with bacterial reverse mutation, mouse erythrocyte micronucleus test and in vitro mammalian cell chromosome aberration test. In the 14-days acute toxicity study, Kunming mice were administered at a dosage of 96 g/kg body weigh by gavage. In the 90-day subchronic toxicity study, Sprague-Dawley rats received oral doses of 0, 3.5, 7 and 14 g/kg body weight of AEVR. In the teratogenicity study, pregnant Sprague-Dawley rats received a dose of 0, 3.5, 7 and 14 g/kg body weight of AEVR. RESULTS: AEVR did not show any genotoxicity based on the bacterial reverse mutation, mouse erythrocyte micronucleus test and in vitro mammalian cell chromosome aberration test. In the acute toxicity study, AEVR at a dose of 96 g/kg body weight did not cause death or abnormal behavior in male or female mice. In the subchronic toxicity study, at the doses of 0, 3.5, 7, 14 g/kg body weight, no dose-related effects on clinical observation, body weight, organ weight, hematology, serum biochemistry and urinalysis of AEVR were detected in male or female rats. Teratogenicity test shown that there were no significant toxicologically changes in embryonic formation, body weight of pregnant rats, external, skeletal and visceral examination observed in pregnant and fetal rats at the dosage of 0, 3.5, 7, 14 g/kg body weight. CONCLUSION: In vivo or in vitro assays demonstrated that AEVR does not exhibit genotoxicity. The LD50 of AEVR was greater than 96 g/kg body weight in both sex of mice according to acute oral toxicity study. Subchronic toxicity and teratogenicity tests showed that the no observed adverse effect level (NOAEL) of AEVR was no less than 14 g/kg body weight. This study established a non-toxic dose of AEVR, providing a foundation for the use of valerian as a new resource food in some countries and regions.
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Pruebas de Mutagenicidad , Extractos Vegetales , Raíces de Plantas , Ratas Sprague-Dawley , Pruebas de Toxicidad Aguda , Pruebas de Toxicidad Subcrónica , Valeriana , Animales , Masculino , Femenino , Extractos Vegetales/toxicidad , Extractos Vegetales/administración & dosificación , Valeriana/química , Ratones , Aberraciones Cromosómicas , Ratas , Pruebas de Micronúcleos , Relación Dosis-Respuesta a Droga , Cricetulus , Embarazo , Células CHO , Animales no ConsanguíneosRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Gynura japonica (Thunb.) Juel is often confused with the non-pyrrolizidine alkaloid-producing herbs, Tu-San-Qi (Sedum aizoon L.) and San-Qi (Panax notoginseng L.), due to similarities in name, appearance, and medicinal use. It contains pyrrolizidine alkaloids, which cause over 50% of cases of hepatic sinus obstruction syndrome. However, the mechanisms underlying G. japonica-induced hepatotoxicity remain poorly understood. AIM OF THE STUDY: In this study, we aimed to investigate the toxic effects of a G. japonica decoction on liver and Buffalo rat liver (BRL) cells and elucidate the associated mechanisms. MATERIALS AND METHODS: This study employed G. japonica decoction and examined its effects on liver function and tissue damage in Sprague-Dawley rats. Bioinformatics analysis was employed to identify gene expression and enriched pathways related to hepatotoxicity. Laser scanning confocal microscopy and flow cytometric annexin V/PI labeling assays were utilized to observe apoptosis in BRL cells induced by G. japonica. Transmission electron microscopy and JC-1 staining were used to determine the effects of G. japonica on mitochondrial ultrastructure and membrane potential in BRL cells. The bicinchoninic acid method and enzyme-linked immunosorbent assays were used to detect the expression of apoptosis-related proteins and caspase-3 activity, respectively. RESULTS: Comparisons of body weight, liver histopathology, and serum liver function-related indices in rats, t showed that exposure to G. japonica may cause liver damage. Bioinformatics analysis indicated that hepatotoxicity might be related to apoptotic signaling pathways, the positive regulation of programmed cell death, and responses to toxic substances. BRL cells exposed to the G. japonica decoction exhibited mid-to late-stage apoptosis and necrosis, along with alterations in mitochondrial morphology and membrane potential. Furthermore, expression of cytochrome C (Cyt C) and pro-apoptotic proteins was increased, anti-apoptotic proteins decreased, and caspase-3 activity elevated. CONCLUSIONS: These findings indicate that G. japonica-induced hepatotoxicity involves the activation of mitochondria-mediated apoptosis. Our research enhances the scientific and theoretical foundation for clinical therapy and improves public awareness of the potential toxicity of herbal remedies.
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Apoptosis , Enfermedad Hepática Inducida por Sustancias y Drogas , Hígado , Ratas Sprague-Dawley , Animales , Apoptosis/efectos de los fármacos , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Ratas , Masculino , Hígado/efectos de los fármacos , Hígado/patología , Hígado/metabolismo , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Búfalos , Hepatocitos/efectos de los fármacos , Hepatocitos/patología , Hepatocitos/ultraestructura , Hepatocitos/metabolismo , Extractos Vegetales/farmacología , Extractos Vegetales/toxicidad , Línea CelularRESUMEN
Phytotoxic compounds isolated and identified from different plants have the ability to use as plant-based herbicides. Phytotoxic chemicals may be essential to weed management and environmental protection in order to reduce the indiscriminate use of synthetic pesticides. It has been reported that Elaeocarpus floribundus plant possesses phytotoxic compounds. The leaf extracts of this species demonstrated significant growth inhibition against the tested plants (dicot plant lettuce and plant monocot timothy) and inhibition was dose- and species-dependent pattern. Two phytotoxic compounds were separated using different purifications methods and identified as compounds 1 and 2. All phytotoxic compounds displayed potent growth limitation against the tested species (cress). The compound concentrations needed for the inhibition of 50% growth (IC50 value) of tested species ranged from 1.06 to 8.53 µM (micromolar). Findings of this research suggest that these compounds might be responsible for the phytotoxicity of Elaeocarpus floribundus plant. The results of this study may be helpful for the development of natural herbicide to control weeds.
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Herbicidas , Extractos Vegetales , Malezas , Herbicidas/farmacología , Herbicidas/toxicidad , Malezas/efectos de los fármacos , Malezas/crecimiento & desarrollo , Extractos Vegetales/farmacología , Extractos Vegetales/química , Extractos Vegetales/toxicidad , Control de Malezas/métodos , Hojas de la Planta/efectos de los fármacos , Hojas de la Planta/químicaRESUMEN
Melia azedarach L. is a Meliaceae that has shown important insecticidal activities. However, few researchers have extensively studied the toxicology of aqueous extracts of M. azedarach (MAE). Therefore, the main objective of this study was to characterize the phyto-eco-toxicological profile of MAE. First, a botanical and phytochemical characterization of MAE was performed using a histological, and metabolomic multi-analytical approach. Second, the toxicological effects on pollinating insects (Apis mellifera ligustica) and soil collembola (Folsomia candida) were evaluated. In addition, acute toxicity was evaluated in zebrafish (Danio rerio) to assess effects on aquatic fauna, and toxicity was determined in human neuroblastoma (SH-SY5Y) and fibroblast (FB-21) cell models. Finally, phytotoxic effects on germination of Cucumis sativus L., Brassica rapa L. and Sorghum vulgare L. were considered. Metabolomic analyses revealed the presence of not only limonoids but also numerous alkaloids, flavonoids and terpenoids in MAE. Histological analyses allowed us to better localize the areas of leaf deposition of the identified secondary metabolites. Regarding the ecotoxicological data, no significant toxicity was observed in bees and collembola at all doses tested. In contrast, severe cardiac abnormalities were observed in zebrafish embryos at concentrations as low as 25 µg/mL. In addition, MAE showed toxicity at 1.6 µg/mL and 6.25 µg/mL in FB-21 and SH-SY5Y cells, respectively. Finally, MAE inhibited seed germination with inhibitory concentrations starting from 5.50 µg/mL in B. rapa, 20 µg/mL in S. vulgare, and 31 µg/mL in C. sativus. Although M. azedarach extracts are considered valuable natural insecticides, their ecological impact cannot be underestimated. Even the use of an environmentally friendly solvent (an aqueous solution), for the first time, is not without side effects. Therefore, the data collected in this study show the importance of evaluating the dosages, modes of administration and production methods of M. azedarach phytoextracts in agricultural settings.
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Melia azedarach , Pez Cebra , Animales , Extractos Vegetales/toxicidad , Ecotoxicología , Humanos , Abejas/efectos de los fármacos , Insecticidas/toxicidad , Germinación/efectos de los fármacosRESUMEN
Mimosa tenuiflora (Fabaceae) is popularly known in Brazil as "Jurema preta". From the bark of its root, "jurema wine" is obtained, a psychedelic drink used in Indigenous religious rituals in Northeastern Brazil. This work aimed to investigate the chemical composition and acute oral toxicity of the ethanolic extract of the root bark from M. tenuiflora (EEMt). EEMt was analyzed by UPLC-QToF-MS/MS and DI-ESI-IT-MSn. Oral administration of EEMt was performed once at doses of 300 and 2000 mg/kg in female Swiss mice. Signs and symptoms of intoxication, as well as mortality were monitored for 14 days. Thirteen compounds were annotated in EEMt: eight type B proanthocyanidins, three alkaloids, a glycosylated flavonol, and a dihydrochalcone derivative. The acute administration of 300 and 2000 mg/kg of EEMt did not show mortality. It also did not change the food intake or body weight of the animals. However, the relative weights of the kidneys were significantly changed for both doses. Changes in hematological and biochemical parameters were found. In addition, histopathological changes were also observed in the heart, liver, and kidneys. Thus, based on our findings, EEMt presented an LD50 greater than 2000 mg/kg and was therefore classified in category 5 of the Globally Harmonized Classification System (GHS). EEMt showed acute oral toxicity by altering hematological, biochemical and histological parameters.
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Mimosa , Corteza de la Planta , Extractos Vegetales , Raíces de Plantas , Animales , Extractos Vegetales/toxicidad , Extractos Vegetales/química , Ratones , Femenino , Corteza de la Planta/química , Raíces de Plantas/química , Mimosa/química , Brasil , Pruebas de Toxicidad Aguda , Espectrometría de Masas en Tándem , Metabolómica , Etanol/químicaRESUMEN
BACKGROUND: Equisetum diffusum D. Don commonly known as 'Himalayan horsetail', has been traditionally used in the treatment of back pain, bone fracture and dislocation, and arthritis by various tribal communities of India. Our previous study confirmed the anti-inflammatory efficacy of the plant through in silico, in vitro, and in vivo model studies. Therefore, the current research is focused on safety dose evaluation for the first-time of the whole-plant methanol extract (EDME) of E. diffusum through appropriate in silico, in vitro, and in vivo approaches. METHOD: The whole plant, along with its rhizomes, was collected, and the methanol extract was prepared. The in silico ADMET study was performed to predict the pharmacokinetics profile and toxicity of all the identified phyto-compounds of EDME previously screened by GC-MS study. In vitro cytotoxicity study of EDME was performed using two cell lines: kidney (HEK293) and liver (Huh7) cell lines. The in vivo toxicity study of EDME was validated by the acute toxicity (OECD 423, 2002) and sub-acute toxicity assays (OECD 407, 2008) in the Wistar Albino rat model. RESULTS: The in silico ADMET study of all 47 bioactives predicted good pharmacokinetic and low toxicity profiles. In vitro cytotoxicity showed higher IC50 values of EDME viz., 672 ± 15.7 µg/mL and 1698 ± 6.54 µg/mL for both kidney (HEK293) and liver (Huh7) cell lines, respectively, which were considered as low-toxic. Based on acute oral toxicity, the LD50 value of the extract was considered "non-toxic" up to a feeding range of 2000 mg/kg of body weight. The regular consumption of the extract for an extended period (28 days) was also qualified as safe based on the body and organ weight, hematological, biochemical, and histoarchitecture results in the sub-acute toxicity assay. CONCLUSION: The detailed in silico, in vitro, in vivo (acute and sub-acute oral toxicity) studies gave us a new insight to the safety dose evaluation of Equisetum diffusum, which may serve as a reliable documentation for undertaking the experimental validation of the ethnobotanical uses of the plant which would help in the field of drug development for the treatment of inflammation related complications.
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Equisetum , Etnobotánica , Extractos Vegetales , Extractos Vegetales/farmacología , Extractos Vegetales/toxicidad , Extractos Vegetales/química , Animales , Humanos , India , Equisetum/química , Ratas , Masculino , Simulación por Computador , Ratas Wistar , Pruebas de Toxicidad Aguda , FemeninoRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: The safety assessment of herbal products is critical for their appropriate pharmacological applications. Garcinia cowa Roxb., commonly known as Cha-muang in Thai, has ethnopharmacological relevance for inflammation, infectious diseases, and diabetes. The leaf extracts of G. cowa have been extensively reported for their anticancer, anti-inflammatory, antimicrobial, and antioxidant effects. Notably, chamuangone is their major active constituent that contributes to various pharmacological properties. AIM OF THE STUDY: The current study aims to establish a standardized chamuangone enriched extract (CEE) and assess its acute and sub-acute toxicities in animal models. METHODOLOGY: CEE was established from G. cowa leaves using a microwave-assisted extraction (MAE), followed by fractionation and enrichment through silica gel vacuum and column chromatography. The concentration of chamuangone in the extract was quantified using a validated quantitative high-performance liquid chromatography (HPLC) method. The safety profiles of CEE were thoroughly evaluated in rodents according to the Organization for Economic Cooperation and Development (OECD) 425 and 407 guidelines. The effects on oxidative stress markers such as superoxide dismutase (SOD), reduced glutathione (GSH), catalase (CAT), and malondialdehyde (MDA) levels were also evaluated in various organs. RESULTS: Based on the quantitative HPLC analysis, the CEE contained 73.0 ± 2.0% w/w of chamuangone. In the acute toxicity study, following up and down procedure the female rats were dosed with CEE at 1750 and 550 mg/kg body weight (b.w.), with CEE 1750 mg/kg b.w. was toxic, causing mortality, while CEE 550 mg/kg b.w. was deemed safe. An LD50 value was calculated according to the standard protocols, resulting in 970 mg/kg b.w. In histopathological examination, 550 mg/kg b.w. of CEE was safe in all the selected organs, while the 1750 mg/kg b.w. CEE treated rats exhibited toxic effects in histological tissues sections in the form of necrosis in the brain, cardiac muscle hypertrophy, liver inflammation, mild untoward effect in the spleen, fibrosis in the lungs, pancreatitis, pyelonephritis, and ovarian cyst. Administration of CEE at doses of 550 mg/kg b.w. (single dose) in the acute and 100 mg/kg b.w. (regularly 28-days) in the sub-acute toxicity studies significantly (p < 0.05) decreased levels of uric acid, triglycerides, and cholesterol. Importantly, the CEE (550 and 100 mg/kg b.w.) also significantly increased the levels of antioxidant enzymes (SOD, GSH, and CAT) and decreased MDA levels. Normal histopathology was observed in the sub-acute toxicity study in all treated groups. CONCLUSION: This study successfully concludes that CEE at a dose of 100 mg/kg b.w. is safe for therapeutic application or use as a chemopreventive functional food utilizing green extraction methods. However, chronic toxicity studies are further recommended to validate safety concerns over an extended period.
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Garcinia , Extractos Vegetales , Hojas de la Planta , Animales , Hojas de la Planta/química , Extractos Vegetales/toxicidad , Extractos Vegetales/farmacología , Extractos Vegetales/química , Extractos Vegetales/administración & dosificación , Garcinia/química , Masculino , Femenino , Ratas , Pruebas de Toxicidad Aguda , Ratones , Ratas Sprague-Dawley , Estrés Oxidativo/efectos de los fármacos , Antioxidantes/farmacología , Antioxidantes/toxicidad , Antioxidantes/aislamiento & purificaciónRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Baccharis milleflora (Less.) DC. is a plant native to Brazil that is frequently used in traditional medicine as a diuretic and antihypertensive. However, even though it is traditionally used for these purposes, its diuretic and hypotensive effects have not been fully elucidated. AIM: Investigate the cardiorenal effects of the ethanol-soluble fraction (ESBM) of Baccharis milleflora in normotensive rats. MATERIALS AND METHODS: Cladodes of B. milleflora were analyzed using light and scanning electron microscopy to provide anatomical data to support quality control. Subsequently, the ESBM was obtained and analyzed using LC-DAD-MS, and its components were annotated. The acute toxicity of ESBM was assessed in female Wistar rats. The acute and prolonged diuretic and hypotensive effects were then studied in Wistar rats. Finally, we assessed the mechanisms responsible for the diuretic effects of ESBM, including the activity of renal Na+/K+/ATPase, angiotensin-converting enzyme, and erythrocyte carbonic anhydrase. Additionally, we also investigated the involvement of bradykinin, prostaglandins, and nitric oxide. RESULTS: From LC-DAD-MS data, thirty-three metabolites were identified from ESBM, including chlorogenic acids, glycosylated phenolic derivatives, C-glycosylated flavones, and O-glycosylated flavonols. No signs of acute toxicity were observed in female rats. The findings showed that ESBM had significant diuretic and natriuretic effects, as well as a potassium-sparing effect. The treatment with ESBM was able to significantly decrease serum levels of creatinine and malondialdehyde, and also significantly increase levels of nitrite, an indirect marker of nitric oxide bioavailability. Furthermore, pre-treatment with L-NAME abolished all diuretic effects induced by ESBM. CONCLUSION: This study presented important morpho-anatomical and phytochemical data that support the quality control of Baccharis milleflora. The ESBM exhibited a significant diuretic and natriuretic effect following acute and seven-days repeated treatment in Wistar rats, without affecting renal potassium elimination. These effects appear to be dependent on the activation of the nitric oxide-cyclic GMP pathway. This study suggests the potential use of B. milleflora preparations in clinical situations where a diuretic effect is needed.
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Baccharis , Diuréticos , Etanol , Extractos Vegetales , Ratas Wistar , Animales , Femenino , Diuréticos/farmacología , Extractos Vegetales/farmacología , Extractos Vegetales/química , Extractos Vegetales/toxicidad , Baccharis/química , Etanol/química , Ratas , Riñón/efectos de los fármacos , Riñón/metabolismo , Riñón/patología , Presión Sanguínea/efectos de los fármacos , Etnofarmacología , Solubilidad , Antihipertensivos/farmacología , Antihipertensivos/aislamiento & purificaciónRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Hancornia speciosa is a medicinal plant popularly used to treat different medical issues, including infectious diseases. Exploring the therapeutic potentialities of the extracts from medicinal plants combined with conventional antibiotic drugs is a promising horizon, especially considering the rising microbial resistance. AIM OF THE STUDY: This study aimed to characterize the chemical composition of the ethereal (EEHS) and methanolic (MEHS) extracts of the stem bark of H. speciosa, and also evaluate their antibacterial and drug-modifying activity, and toxicity. MATERIALS AND METHODS: The extracts were characterized by gas chromatography coupled to mass spectrometry (GC-MS). Additionally, total phenol and flavonoid contents were determined. The antibacterial and antibiotic-modifying activity was evaluated against strains of Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa using the serial microdilution method, obtaining the minimum inhibitory concentration (MIC). The toxicity assay was carried out using the Drosophila melanogaster model. RESULTS: Thirty compounds were identified in the extracts of the stem bark of H. speciosa, with triterpenoids being predominant in both extracts. Additionally, fatty alcohols, carbohydrates, fatty acids, phenolic acids, and phytosterols were identified in both extracts. EEHS and MEHS extracts had considerable phenol contents (346.4 and 340.0 mg GAE/g, respectively). Flavonoids were detected in a lower proportion (7.6 and 6.9 mg QE/g, respectively). H. speciosa extracts did not display intrinsic antibacterial activity against the bacterial strains evaluated, however, they were capable of modifying the activity of gentamicin, erythromycin, and norfloxacin. EEHS increased the efficacy of norfloxacin against E. coli and S. aureus, reducing MIC values by 50%. MEHS potentiated the action of gentamicin against all bacterial strains, especially against E. coli. The extracts did not display toxicity at clinically relevant concentrations against D. melanogaster. CONCLUSION: The stem bark of H. speciosa was considered a rich source of bioactive compounds. Our findings evidenced the therapeutic potential of H. speciosa extracts for the development of new pharmaceutical therapeutics against bacteria. Although the extracts did not exhibit intrinsic antibacterial activity, they enhanced the efficacy of commercial antibiotic drugs and were non-toxic at clinically relevant concentrations. Future studies are needed to elucidate the mechanisms of action of these extracts, ensuring their safety and efficacy.
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Antibacterianos , Apocynaceae , Pruebas de Sensibilidad Microbiana , Corteza de la Planta , Extractos Vegetales , Extractos Vegetales/farmacología , Extractos Vegetales/toxicidad , Extractos Vegetales/química , Antibacterianos/farmacología , Antibacterianos/toxicidad , Antibacterianos/química , Corteza de la Planta/química , Animales , Apocynaceae/química , Staphylococcus aureus/efectos de los fármacos , Drosophila melanogaster/efectos de los fármacos , Escherichia coli/efectos de los fármacos , Pseudomonas aeruginosa/efectos de los fármacos , Tallos de la Planta/química , Cromatografía de Gases y Espectrometría de MasasRESUMEN
ETHNOPHARMACOLOGICAL SIGNIFICANCE: Elsholtiza bodinieri Vaniot, belonging to the family Lamiaceae, has important medicinal value in Yunnan province of China. Traditionally, its aerial parts have been used as an ethnomedicine to treat diaphoresis, headache, fever, cough, pharyngitis, dyspepsia, and hepatitis. However, the safety assessment of E. bodinieri is still unexplored. AIM OF THE STUDY: This study aimed to investigate the phytochemical constituents of the hot water extract from E. bodinieri (HEEB) and evaluate the 14-day acute, 28-day subacute and 90-day subchronic toxicity by oral administration in Sprague-Dawley (SD) rats. MATERIALS AND METHODS: The chemical constituents of HEEB were analyzed by UHPLC-ESI-HRMS/MS. Firstly, SD rats were chosen for a single oral administration of the maximum dose of 5000 mg/kg to evaluate toxicity. Subsequently, consecutive 28-day subacute and 90-day subchronic toxicity assessments of HEEB were conducted on Sprague-Dawley (SD) rats through repeated doses of 2500, 1250, 625, and 312.5 mg/kg for the former, and 1500, 1000, and 500 mg/kg for the latter. For toxicity evaluation, hematology and serum biochemical indicators were determined, and major organs of the rats were collected to calculate organ coefficients. Additionally, hematoxylin-eosin (H&E) staining was performed on the collected tissues to assess histopathological changes induced by repeated oral administration of HEEB. RESULTS: A total of 23 compounds were identified by UHPLC-ESI-HRMS/MS analysis. Acute toxicity assessment revealed that oral administration of HEEB did not induce mortality and unnormal behavior changes in female rats over a 14-day period, suggesting that the approximate lethal dose (ALD) was higher than 5000 mg/kg. In consecutive 28-day and 90-day toxicity evaluations, HEEB doses of 2500 mg/kg and 1500 mg/kg resulted in hepatic and kidney tissue damage in both female and male rats, which was verified by the increased levels of AST, ALT, BUN, Na+, and Cl-. CONCLUSIONS: After the acute, 28-day subacute and 90-day subchronic toxicity evaluation, the No Observed Adverse Effect Level (NOAEL) was determined as 1000 mg/kg/day. These findings not only provided a safety information for its medicinal and edible application, but also promoted the further comprehensive development of this plant.
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Extractos Vegetales , Ratas Sprague-Dawley , Pruebas de Toxicidad Aguda , Pruebas de Toxicidad Subcrónica , Animales , Masculino , Femenino , Extractos Vegetales/toxicidad , Extractos Vegetales/administración & dosificación , Ratas , Lamiaceae/química , Plantas Medicinales/toxicidad , Fitoquímicos/toxicidad , Fitoquímicos/análisis , Pruebas de Toxicidad Subaguda , Administración Oral , Relación Dosis-Respuesta a DrogaRESUMEN
To find a high-efficiency and environment-friendly biogenic molluscicide against Oncomelania hupensis, and prevent aquatic ecosystem from being contaminated by chemical molluscicides and being toxic. We extracted and purified raphides from the tubers of Arisaema erubescent, and determined the active constituents and molluscicidal activity of the raphides, detoxification enzyme activity, and liver damage. The results showed that the raphides had a strong molluscicidal activity. O. hupensis snails were exposed to the lethal concentration (LC50) of 70.95â¯mg/L and 44.25â¯mg/L for treatment with raphides for 48â¯h and 72â¯h, respectively. The raphides of molluscicidal activity of the main constituents was as follows: intact raphides > calcium oxalate crystals > AEL (Arisaema erubescens Lectin). The activities of peroxidase (POD), superoxide dismutase (SOD) and catalase (CAT) in the snail livers increased significantly at the early stage of treatment (24â¯h), but decreased sharply in the later stage (120â¯h), compared with that in the control group. The results indicated that after treatment with 1/2 LC50 raphides for 120â¯h, the activities of POD, SOD, and CAT in the snail livers decreased by 82.5â¯%, 62.9â¯%, and 84.7â¯%, respectively. In addition, electron micrographs have shown that the raphides were needle-shaped crystals and tended to be sharp at both ends (with a groove down both sides) and some were barbed, which caused damage to the snail livers to different extent. Overall, our results indicate that the mechanism of toxicity of raphides against O. hupensis may be that the calcium oxalate crystals pricked the liver surface of snail and produced mechanical damage; and then the harmful protease AEL in the raphides was injected into the liver, which reduced the activities of detoxification enzymes, produced severe toxic reactions and eventually killed the O. hupensis snails.
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Catalasa , Moluscocidas , Caracoles , Animales , Moluscocidas/toxicidad , Caracoles/efectos de los fármacos , Catalasa/metabolismo , Hígado/efectos de los fármacos , Superóxido Dismutasa/metabolismo , Extractos Vegetales/farmacología , Extractos Vegetales/química , Extractos Vegetales/toxicidad , Peroxidasa/metabolismo , Tubérculos de la Planta/química , Dosificación Letal MedianaRESUMEN
The present study aims to assess the acute and subacute toxicity of the hydro-alcoholic extracts of Anchusa strigosa (leaves) and the aerial parts of Zataria multiflora Boiss in Wistar albino rats. The crude extracts of Anchusa strigosa (leaves) and the aerial parts of Zataria multiflora Boiss were prepared in 70% ethanol. Systematic tests for acute toxicity were performed at varying dosages of 100, 250, and 500 mg/kg, while for subacute toxicity, a dose of 600 mg/kg was orally given to Wistar albino rats. At the end of acute and sub-acute toxicity studies, biochemical parameters, hematological analysis, and histopathological analysis showed no significant difference in the body weight, abnormalities, or organ damage of the rats compared to the untreated rats (control). Also, there were no results of death recorded in rats. These findings indicated that the medium-term oral administration of Anchusa strigosa (leaves) and the aerial parts of Zataria multiflora Boiss after the treatment does not cause toxicity and provides assurance regarding their suitability for potential therapeutic applications in both acute and subacute forms.
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Componentes Aéreos de las Plantas , Extractos Vegetales , Ratas Wistar , Pruebas de Toxicidad Aguda , Animales , Extractos Vegetales/toxicidad , Ratas , Componentes Aéreos de las Plantas/química , Lamiaceae/química , Hojas de la Planta/química , Pruebas de Toxicidad Subaguda , Masculino , FemeninoRESUMEN
Background: The Mediterranean thistle Atractylis gummifera L. (Asteraceae; AG) has diterpenoid glucosides; atractyloside and carboxyatractyloside that interact with mitochondrial protein adenine nucleotide translocator (ANT) and resulted in ATP inhibition. Despite its well-known toxicity, acute poisonings still occur with this plant. Although most symptoms are attributed to ANT and diterpenoids interaction, in-depth investigation of the effects of AG extract on various cellular processes has not been performed. Objective/method: We tested in vitro induction of mitochondrial permeability transition pore (MPTP) opening in bovine liver mitochondria and evaluated its cytotoxicity and genotoxicity using Allium cepa test. Cell division, mitotic index (MI) and total chromosomal and mitotic aberrations (TAs), that all seem potentially affected by ATP shortage, were studied in root cells of Allium cepa exposed to Atractylis gummifera extract. Results: With the two different doses of two purified AG fractions, stronger induction of MPTP was observed compared to the induction with the standard pure atracyloside. Aqueous AG extract exerted inhibition root growth in A. cepa at 6 different doses. The TAs was increased in a dose-dependent manner too, while mitotic index was decreased at the same doses. Evaluation of mitotic phases revealed mitodepressive effect of AG on A. cepa roots. Conclusion: this work highlights cellular and mitochondrial adverse effects of Atractylis gummifera extracts. A purified fraction that likely corresponds to ATR derivatives induces MPTP opening leading to swelling of mitochondria and its dysfunction. Allium cepa test provides the evidence for A. gummifera genotoxicity and cytotoxicity.