Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 5.300
Filtrar
1.
Braz. j. biol ; 83: e244551, 2023. tab, graf
Artigo em Inglês | MEDLINE, LILACS, VETINDEX | ID: biblio-1285626

RESUMO

Abstract Origanum vulgare has been of great interest in academia and pharma industry due to its antioxidant, antifungal and antitumor properties. The present study aimed to find the anti-MRSA potential and in vivo toxicity assessments of O. vulgare. O. vulgare extract was used to monitor anti-MRSA activity in mice. Following MRSA established infection in mice (Mus musculus), treatment with O. vulgare was continued for 7 days. Autopsies were performed and re-isolation, gross lesion scoring and bacterial load in various organs were measured. Additionally, blood sample was analysed for hematological assays. Toxicity assessment of O. vulgare potential as medicine was done at 200 mg/kg and 400 mg/kg by evaluating liver and kidney functions. Bacterial load and gross lesion in lungs and heart were significantly low compared to positive control following O. vulgare treatment. Likewise, O. vulgare treated groups had hematological, neutrophil and TLC values similar to control groups. Increased AST, ALP and total bilirubin alongwith marked hepatocellular degeneration and distortion around the central vein, inflammatory cell infiltration, and cytoplasmic vacuolization of hepatic cells was observed at higher dose. It is concluded that crude extract of O. vulgare may contain beneficial secondary metabolites and in future may be explored for curing infectious diseases.


Resumo Origanum vulgare tem despertado grande interesse na academia e na indústria farmacêutica devido às suas propriedades antioxidantes, antifúngicas e antitumorais. O presente estudo teve como objetivo encontrar o potencial anti-MRSA e avaliações de toxicidade in vivo de O. vulgare. O extrato de O. vulgare foi usado para monitorar a atividade anti-MRSA em camundongos. Após infecção estabelecida por MRSA em camundongos (Mus musculus), o tratamento com O. vulgare foi continuado por 7 dias. As autópsias foram realizadas e o reisolamento, pontuação das lesões grosseiras e carga bacteriana em vários órgãos foram medidos. Além disso, a amostra de sangue foi analisada para ensaios hematológicos. A avaliação da toxicidade do potencial de O. vulgare como medicamento foi feita com 200 mg / kg e 400 mg / kg, avaliando as funções hepática e renal. A carga bacteriana e as lesões graves nos pulmões e no coração foram significativamente baixas em comparação com o controle positivo após o tratamento com O. vulgare. Da mesma forma, os grupos tratados com O. vulgare apresentaram valores hematológicos, de neutrófilos e de TLC semelhantes aos grupos de controle. Aumento de AST, ALP e bilirrubina total juntamente com degeneração hepatocelular marcada e distorção ao redor da veia central, infiltração de células inflamatórias e vacuolização citoplasmática de células hepáticas foram observados em doses mais altas. Conclui-se que o extrato bruto de O. vulgare pode conter metabólitos secundários benéficos e, no futuro, pode ser explorado para a cura de doenças infecciosas.


Assuntos
Animais , Coelhos , Óleos Voláteis , Origanum , Anti-Infecciosos/toxicidade , Extratos Vegetais/toxicidade , Fígado , Antioxidantes
2.
Biomed Res Int ; 2022: 5281660, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35402613

RESUMO

Turmeric rhizome (Curcuma longa L.) has been used without concern for safety as a culinary spice and traditional medicine under the ancient Ayurvedic medicinal system of India dating back nearly 4000 years. This preclinical safety evaluation was done to determine the safety of an oleoresin-based turmeric extract (CURCUGEN®). Guidelines from the Organization for Economic Co-operation and Development (OECD) directed the assessment of safety for the in vitro and in vivo application of CURCUGEN®. Safety of the herbal medicine was evaluated through the toxicological assessment of acute, oral, and 90-day repeated dosing, genotoxicity, and mutagenicity study. Genotoxicity tests included the in vitro bacterial reverse mutation test, chromosomal aberration test, and in vivo micronucleus test. The single dose of CURCUGEN® administered orally (gavage) to Sprague-Dawley (SD) rats resulted in a LD50 of >5000 mg/kg body weight. The subchronic assessment of CURCUGEN®, as administered to SD rats over 90 days resulted in a no observed adverse effect level (NOAEL) of 2000 mg/kg body weight/day. CURCUGEN® did not elicit any genotoxic or clastogenic effect in genotoxicity tests. The battery of safety studies carried out demonstrated that CURCUGEN® showed no evidence of general toxicity or genotoxicity.


Assuntos
Curcuma , Extratos Vegetais , Administração Oral , Animais , Peso Corporal , Dano ao DNA , Testes de Mutagenicidade , Mutagênicos , Extratos Vegetais/toxicidade , Ratos , Ratos Sprague-Dawley , Testes de Toxicidade Aguda , Testes de Toxicidade Subcrônica
3.
J Ethnopharmacol ; 292: 115102, 2022 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-35288288

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The genus Sambucus L. (Viburnaceae) consists of about 29 recognized species distributed in all regions of the world except the extremely cold and desert areas. Some species have been used as traditional medicines to treat various disorders such as bone fractures, rheumatism, diabetes, respiratory and pulmonary disorders, skin diseases, inflammatory ailments, diarrhea, and others. However, the currently available data on traditional and pharmacological uses have not been comprehensively reviewed. STUDY AIM: The present review is designed to provide information on the ethnobotanical uses, phytochemistry, toxicity, and the known biological properties of Sambucus, to understand their connotations and provide a scientific basis and gaps for further research. MATERIALS AND METHODS: The information was obtained from different bibliographic databases, Google Scholar, Springer Link, Web of Science, PubMed, and Science Direct along with other literature sources such as dissertation before August 2021. The scientific names were validated using The Plant List and World Flora Online websites. RESULTS: Twelve Sambucus species were found to be frequently mentioned in ethnomedical uses recorded in China, Korea, Turkey, Iran, and other countries. Traditionally, they have been used as remedies to numerous health complications among others, bone fractures and rheumatism, diabetes, wounds, inflammatory diseases, diarrhea, menstrual pains, respiratory and pulmonary complaints, skin disorders, headaches, snakebites, and urinary tract infections. To date, only eleven species have been studied for their chemical compounds and a total of 425 bioactive constituents, including phenolic compounds, terpenoids, fatty acids, cyanogenic glycosides, phytosterols, lectins, organic acids, alkaloid, coumarin, anthraquinone, and others have been reported. The crude extracts and the isolated chemical constituents exhibited diverse outstanding pharmacological activities including antioxidant, antimicrobial, antidiabetic, anti-inflammatory, antidepressant, analgesic, anti-giardial, immunomodulatory, scolicidal, anti-ulcerogenic, antiradical, bone-protective, anti-glycemic, antiosteoporotic, hypolipidemic, anti-glycation, and wound-healing properties. CONCLUSION: This study summarized and scrutinized the data on traditional uses, pharmacological activities, phytochemicals, and toxicity of Sambucus species, which indicate they have interesting chemical compounds with diverse biological activities. Many traditional uses of some species from this genus have now been confirmed by pharmacological activities, such as antioxidant, antimicrobial, bone-protective, wound healing, anti-inflammatory, and analgesic properties. However, the currently available data has several gaps in understanding the traditional uses of all Sambucus species. Thus, we strongly recommend further investigations into the scientific connotations between traditional medicinal uses and pharmacological activities, mode of action of the isolated bioactive constituents, and toxicity of other Sambucus species to unravel their efficacy and therapeutic potential for safe clinical application. The current extensive study avails valuable information on therapeutic use of Sambucus species and paves way for further investigations of other useful species, as well as drug discovery.


Assuntos
Anti-Infecciosos , Fraturas Ósseas , Doenças Reumáticas , Sambucus , Analgésicos , Antioxidantes , Diarreia/tratamento farmacológico , Etnobotânica , Etnofarmacologia , Humanos , Compostos Fitoquímicos/química , Compostos Fitoquímicos/toxicidade , Fitoterapia , Extratos Vegetais/uso terapêutico , Extratos Vegetais/toxicidade , Doenças Reumáticas/tratamento farmacológico
4.
ScientificWorldJournal ; 2022: 5953094, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35250394

RESUMO

AIMS: The aim of this study was to compare the phytochemical profile and acute and chronic toxicity of hydroethanolic extracts of three parts of P. santalinoides. METHODS: Seven major chemical groups (alkaloids, flavonoids, saponosides, coumarins, tannins, triterpenes, and steroids) were studied. The single dose limit test of 5000 mg/kg body weight was used to evaluate the acute toxicity of each organic extract. Subacute toxicity was evaluated after daily oral doses of 500 and 1000 mg/kg body weight were administered to rats for 28 days. RESULTS: At a single dose of 5000 mg/kg, none of the extracts (leaf, trunk bark, and root) caused death in experimental rats. However, the trunk bark extract of P. santalinoides induced coat change and lethargy in treated rats. Macroscopic observation of the internal organs (liver and kidneys) of the rats showed no abnormalities. In the subacute test, only the trunk extracts induced signs of toxicity such as mobility disorders, diarrhea, and loss of body weight at a dose of 1000 mg/kg. CONCLUSION: This study showed that the hydroethanol extracts of the leaves, trunk bark, and root bark of P. santalinoides divergently concentrated the main chemical groups of interest. Administration of a single dose of extracts from all three P. santalinoides is not toxic to the consumer. However, when used over a long period of time, they can have a harmful effect on the consumer. In view of the different results of the trunk bark extract and in a context of conservation of the species, we recommend the use of the hydroethanolic extract of the leaves in the different treatments in which the three organs are involved.


Assuntos
Casca de Planta/química , Extratos Vegetais/toxicidade , Folhas de Planta/química , Raízes de Plantas/química , Pterocarpus/química , Administração Oral , Animais , Relação Dose-Resposta a Droga , Feminino , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Masculino , Extratos Vegetais/administração & dosagem , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Ratos , Ratos Wistar , Testes de Toxicidade
5.
BMC Complement Med Ther ; 22(1): 72, 2022 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-35296314

RESUMO

BACKGROUND: In response to the persistent problem of malaria resistance, medicinal herbal plants can be used as a source of potential novel antimalarial agents. Therefore, the aim of this study was to evaluate the in vivo antimalarial activity and toxicity of an ethanolic seed extract of Spondias pinnata (L.f.) Kurz (S. pinnata). METHODS: Qualitative phytochemical screening of the extract was performed using standard procedures, and the constituents were determined by gas chromatography-mass spectrometry (GC-MS). The in vivo antimalarial activity was assessed against the Plasmodium berghei ANKA strain in mice based on 4-day suppressive, curative and prophylactic tests. In addition, the acute toxicity of the extract was evaluated after oral administration of a single dose of 2,000 mg/kg body weight. RESULTS: Phytochemical screening tests on the ethanolic S. pinnata seed extract revealed the presence of terpenoids, tannins, and coumarins. GC-MS analysis of the extract led to the identification of twenty-nine phytochemical compounds, including oleic acid amide, ß-sitosterol, linoleic acid, oleic acid, protocatechuic acid, syringic acid and gallic acid. The results of the 4-day suppressive test revealed that mice treated with 250, 500, 600 and 800 mg/kg doses of the ethanolic S. pinnata seed extract showed significant parasitemia suppression in a dose-dependent manner, with 22.94, 49.01, 60.67 and 66.82% suppression, respectively, compared to that of the negative control group. All the doses of the ethanolic seed extract significantly suppressed parasitemia (P < 0.05) during the curative activity test and prolonged the mean survival time compared to those of the negative control group. However, the ethanolic seed extract displayed lower curative and prophylactic activities than the standard drug artesunate. In addition, the ethanolic seed extract showed no signs of toxicity in mice at a dose of 2,000 mg/kg body weight. CONCLUSION: The S. pinnata seed extract contains various phytochemical compounds with important medicinal properties. The extract showed a significant suppression of parasitemia in a dose-dependent manner, prolonged the mean survival time and exhibited significant curative and prophylactic activities. The overall results of this study demonstrated that the S. pinnata seed extract possessed promising in vivo antimalarial activity against P. berghei ANKA, with no toxicity. The findings from the present study provide scientific evidence supporting the use of S. pinnata seeds in the development of new drugs for malaria treatment. Additional studies are needed to isolate and identify the active compounds as well as to understand the mechanism of inhibition.


Assuntos
Anacardiaceae , Antimaláricos , Animais , Antimaláricos/química , Antimaláricos/toxicidade , Camundongos , Extratos Vegetais/química , Extratos Vegetais/toxicidade , Plasmodium berghei , Sementes
6.
J Toxicol Environ Health A ; 85(11): 461-479, 2022 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-35189780

RESUMO

Yerba mate (Ilex paraguariensis A. St.-Hil.) is an important source of biologically active compounds with pharmacological potential. The aim of this study was to examine the toxicity of different extracts obtained from either traditional or organic cultivated yerba mate in vitro and in vivo. Aqueous, ethanolic and methanolic extracts were obtained from commercial samples of yerba mate and total phenolic content was determined employing Folin-Ciocalteau reagent. The aqueous extracts presented higher content of total phenols, compared to ethanolic and methanolic extracts, and also demonstrated lower cytotoxicity, which is the basis for testing were carried out only using aqueous extracts. The main phenolic acids found in traditional aqueous (TA) extract were chlorogenic, gallic and protocatechuic acids. Gallic and hydroxybenzoic acids were detected in aqueous cultivated organic (OA) extract. Pretreatment with OA extract (100 µg/ml, 1 hr) was cytoprotective against rotenone-induced toxicity (1 µM). For in vivo toxicity assay, zebrafish embryos were exposed to OA or TA extracts (10-160 µg/ml) at 4 hr post fertilization. TA extract decreased embryos survival in a concentration-dependent manner, reduced the hatching rate at 40 µg/ml, increased edema frequency at 80 µg/ml and altered body curvature at 120 µg/ml. Further, TA extract produced locomotor disorders at concentrations equal to or greater than 10 µg/ml. In contrast, OA extract exhibited no apparent toxic effect on organogenesis and behavior up to 100 µg/ml. In summary, the OA cultivated extract showed the lowest cytotoxicity in vitro, enhanced reduction in rotenone-induced toxicity, and produced less toxicity in zebrafish embryos compared to the TA extract.


Assuntos
Ilex paraguariensis , Animais , Ilex paraguariensis/toxicidade , Fenóis/toxicidade , Extratos Vegetais/toxicidade , Peixe-Zebra
7.
Molecules ; 27(3)2022 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-35164354

RESUMO

Plant-derived natural products are significant resources for drug discovery and development including appreciable potentials in preventing and managing oxidative stress, making them promising candidates in cancer and other disease therapeutics. Their effects have been linked to phytochemicals such as phenolic compounds and their antioxidant activities. The abundance and complexity of these bio-constituents highlight the need for well-defined in vitro characterization and quantification of the plant extracts/preparations that can translate to in vivo effects and hopefully to clinical use. This review article seeks to provide relevant information about the applicability of cell-based assays in assessing anti-cytotoxicity of phytochemicals considering several traditional and current methods.


Assuntos
Antioxidantes/toxicidade , Antioxidantes/uso terapêutico , Compostos Fitoquímicos/toxicidade , Compostos Fitoquímicos/uso terapêutico , Animais , Humanos , Estresse Oxidativo , Extratos Vegetais/uso terapêutico , Extratos Vegetais/toxicidade , Testes de Toxicidade
8.
BMC Complement Med Ther ; 22(1): 50, 2022 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-35216561

RESUMO

BACKGROUND: Pain and inflammation are associatory events in cancer, diabetes, cardiovascular diseases, arthritis and other chronic diseases. Corticosteroids, non-steroidal anti-inflammatory drugs exert potential side effects on long term use. This study was aimed to investigate the acute oral toxicity, anti-inflammatory and analgesic activities of leaf and bark extracts of Albizia procera in experimental animal models. METHODS: Ethyl acetate, ethanol, and hydroalcoholic extracts of Albizia procera (leaf and bark) were subjected for acute oral toxicity, anti-inflammatory and analgesic screening. Carrageenan and cotton pellet granuloma models were used to assess acute and chronic anti-inflammatory effects, respectively. Intraplanar formalin test was used to assess the analgesic activity. RESULTS: All the extracts of Albizia procera were found to be well-tolerated up to 2000 mg/kg in female rats. Ethanolic leaf (ETLE) and bark (ETBE) of Albizia procera showed anti-inflammatory actions. But, only ETBE produced significant protection in chronic inflammation and analgesic activity. CONCLUSION: In summary, Albizia procera possess significant anti-inflammatory and analgesic properties. This study adds evidence on the traditional use of Albizia procera plant for treating painful inflammatory disorders.


Assuntos
Albizzia , Analgésicos/uso terapêutico , Analgésicos/toxicidade , Animais , Anti-Inflamatórios/toxicidade , Porcelana Dentária , Ligas Metalo-Cerâmicas , Casca de Planta , Extratos Vegetais/uso terapêutico , Extratos Vegetais/toxicidade , Folhas de Planta , Ratos , Titânio
9.
Pharm Biol ; 60(1): 282-293, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35138992

RESUMO

CONTEXT: Cordia dichotoma Forst. (Boraginaceae) has potent pharmacological impact. Meanwhile, its effect on fertility is unclear. OBJECTIVE: This study investigates the effect of Cordia fresh fruits hydroethanolic extract on fertility. MATERIALS AND METHODS: 120 Wistar albino male rats were divided into four groups (n = 30). The first group was negative control, and the second, third, and fourth groups received 125, 250, and 500 mg extract/kg bodyweight for 56 days. After 56 days, Cordia force-feeding stopped, and all groups were kept under laboratory conditions for another month to study the recovering effect. RESULTS: After day 56, extract at 500 mg/kg significantly reduced sperm total count, motility%, and alive%, to 47.60 ± 2.27 × 106 sperm/mL, 43.33% ± 1.49, and 63.67% ± 1.19, respectively, abnormalities% increased considerably (26.67% ± 0.54), compared to the negative control. Also, significant depletion on follicle-stimulating hormone (2.66 ± 0.21 mIU/L), luteinizing hormone (1.07 ± 0.06 mIU/L), and testosterone (2.69 ± 0.13 nmol/L) level was recorded, compared to the negative control. Cordia negative effect showed on histopathological studies of testes, prostate, and seminal vesicles. Fortunately, these adverse effects of Cordia recovered remarkably after stopping administration for one month. CONCLUSIONS: Cordia antifertility effect may be due to its hypocholesterolemic effect, where cholesterol, the steroid cycle precursor, was significantly reduced. This study can be incorporated in clinical research after being repeated on another small experimental animal, their offspring, and one large experimental animal, then going to a clinical study that we plan to do in the future.


Assuntos
Cordia/química , Extratos Vegetais/toxicidade , Espermatozoides/efeitos dos fármacos , Testículo/efeitos dos fármacos , Animais , Anticolesterolemiantes/administração & dosagem , Anticolesterolemiantes/isolamento & purificação , Anticolesterolemiantes/toxicidade , Relação Dose-Resposta a Droga , Hormônio Foliculoestimulante/metabolismo , Frutas , Hormônio Luteinizante/metabolismo , Masculino , Extratos Vegetais/administração & dosagem , Ratos , Ratos Wistar , Testículo/patologia , Testosterona/metabolismo
10.
Regul Toxicol Pharmacol ; 131: 105144, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35218873

RESUMO

Ziziphus mauritana Lam leaves were used to treat asthma, diabetes, pain, and inflammation in the Indian traditional system of medicine. The leaves of the Ziziphus mauritiana Lam were consumed as a vegetable in Indonesia and India. The present study aims to predict the pharmacokinetic properties of flavonoids identified & quantified through U(H)PLC and to evaluate the safety of methanol extract of Ziziphus mauritana Lam leaves (MEZ) in rats. A U(H)PLC-ESI-QTOF-MS/MS was performed to identify flavonoids present in MEZ and quantified using U(H)PLC method. The in-silico ADME properties of the flavonoids were analyzed using Schrodinger Maestro software. The acute oral toxicity study was performed by administering a single dose of MEZ (5000 mg/kg) in female rats and observed for 14 days. The sub-chronic studies were carried out by oral administration of MEZ at 500, 750, and 1000 mg/kg daily for 90 days. The changes in hematological parameters, clinical biochemistry, and histopathology were observed after the treatment period. Eight flavonoids rutin, kaempferol, luteolin, myricetin, catechin, and apigenin were identified from were identified in UPLC-QTOF-MS/MS analysis. These results showed the highest amount of luteolin (5.41 µg/ml) and kaempferol (4.02 µg/ml) present in MEZ. No signs of toxicity or mortality were observed in acute toxicity studies. In the sub-chronic studies, data showed that MEZ does not produce any changes in hematological and clinical biochemical parameters compared to control rats. MEZ (1000 mg/kg) significantly (p < 0.05) reduced total cholesterol, triglycerides, in male rats, which was more prominent on day 90. The histopathological analysis also revealed no changes in the vital organs. These results conclude that MEZ was considered safe and well-tolerated in rats.


Assuntos
Ziziphus , Animais , Feminino , Flavonoides/toxicidade , Quempferóis/análise , Luteolina/análise , Masculino , Metanol , Extratos Vegetais/química , Extratos Vegetais/toxicidade , Folhas de Planta/química , Ratos , Padrões de Referência , Espectrometria de Massas em Tandem , Ziziphus/química
11.
Anim Biotechnol ; 33(1): 193-199, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35105278

RESUMO

To explore the newer saponin resources, in vitro toxicity of saponin-enriched fraction (SEF) extracted from Silene vulgaris(SV) was evaluated for first time and compared with in vitro toxicity of SEF extracted from Sapindus mukorossi (SM) and Chlorophytum borivilianum (CV). All extracted SEF from diverse resources were characterized by immersing TLC plates in 0.5% RBC suspension method, by ethanol: sulfuric acid method and by estimating hRst values. Each extracted SEF clearly portrayed specific pattern with varied hRst range. White spots against a pinkish-red background and greenish-black spots in case of immersion method and spraying method respectively were observed. After initial characterization, in vitro 0.5% sheep RBC lytic activities and VERO cell cytotoxic activities (via SRB assay) of each extracted SEF were also evaluated. Furthermore, SEF of SV showed very less hemolytic activity compared to SM and CB. The HD50 values for SV, SM, and CB were 736.7 ± 2.824, 18.0 ± 1.894, and 170.70 ± 2.783 µg/mL, respectively. SEF of SV (IC50 ≥ 200 µg/mL) was less toxic for VERO cell line than SEF of SM (IC50 = 150.8 µg/mL) and CB (IC50 = 137.1 µg/mL). Hence, the SEF of SV was found to be less toxic and can be used as a new and safer source of saponins.


Assuntos
Antineoplásicos , Sapindus , Saponinas , Silene , Animais , Extratos Vegetais/toxicidade , Saponinas/toxicidade , Ovinos
12.
BMC Complement Med Ther ; 22(1): 51, 2022 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-35219319

RESUMO

BACKGROUND: Novel potent antimalarial agents are urgently needed to overcome the problem of drug-resistant malaria. Herbal treatments are of interest because plants are the source of many pharmaceutical compounds. The Mahanil-Tang-Thong formulation is a Thai herbal formulation in the national list of essential medicines and is used for the treatment of fever. Therefore, this study aimed to evaluate the antimalarial activity of medicinal plants in the Mahanil-Tang-Thong formulation. METHODS: Nine medicinal plant ingredients of the Mahanil-Tang-Thong formulation were used in this study. Aqueous and ethanolic extracts of all the plants were analyzed for their phytochemical constituents. All the extracts were used to investigate the in vitro antimalarial activity against Plasmodium falciparum K1 (chloroquine-resistant strain) by using the lactate dehydrogenase (pLDH) method and cytotoxicity in Vero cells by using the 3-(4,5-dimethylthiazol2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Additionally, an extract with potent in vitro antimalarial activity and no toxicity was selected to determine the in vivo antimalarial activity with Peters' 4-day suppressive test against the Plasmodium berghei ANKA strain. Acute toxicity was evaluated in mice for 14 days after the administration of a single oral dose of 2000 mg/kg. RESULTS: This study revealed that ethanolic extracts of Sapindus rarak DC., Tectona grandis L.f., Myristica fragrans Houtt. and Dracaena loureiri Gagnep. exhibited potent antimalarial activity, with half-maximal inhibitory concentration (IC50) values of 2.46, 3.21, 8.87 and 10.47 µg/ml, respectively, while the ethanolic of the formulation exhibited moderate activity with an IC50 value of 37.63 µg/ml and its aqueous extract had no activity (IC50 = 100.49 µg/ml). According to the in vitro study, the ethanolic wood extract of M. fragrans was selected for further investigation in an in vivo mouse model. M. fragrans extract at doses of 200, 400, and 600 mg/kg body weight produced a dose-dependent reduction in parasitemia by 8.59, 31.00, and 52.58%, respectively. No toxic effects were observed at a single oral dose of 2000 mg/kg body weight. CONCLUSION: This study demonstrates that M. fragrans is a potential candidate for the development of antimalarial agents.


Assuntos
Antimaláricos , Animais , Antimaláricos/toxicidade , Chlorocebus aethiops , Camundongos , Extratos Vegetais/química , Extratos Vegetais/toxicidade , Plasmodium berghei , Plasmodium falciparum , Células Vero
13.
Braz J Biol ; 84: e254552, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35137848

RESUMO

Anti-tuberculosis drugs are reported to cause hepatotoxicity, which varies from asymptomatic rise of the hepatic enzymes. Hepatoprotective plants plays important role to protect liver. This study investigated the hepatoprotective potential of the Solanum lycopersicum in rats intoxicated with Isoniazid and Rifampicin (INH+RIF) to induce hepatotoxicity. Thirty wistar albino rats were divided into five groups of six animals each. Group 1 rats were kept control while groups II, III, IV and V were administered with INH+RIF (75+150 mg/kg) orally, for seven consecutive days. For treatment, rats in group III received silymarin while animals in group IV and V were provided with 40 mg/kg and 80 mg/kg of Solanum lycopersicum extract, respectively. On day 0 and 8th blood samples were collected for the analysis of hepatic biomarkers. The data were subjected to one-way ANOVA and Bonferroni's post hoc test for statistical analysis. Hepatotoxicity induced by INH+RIF resulted in significant elevation of serum hepatic enzymes including Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Alkaline phosphatase (ALP), and total bilirubin while decreased the albumin level. The Solanum lycopersicum at dose of 80 mg/kg significantly reduced the hepatic enzymes AST, ALT, ALP and bilirubin while the albumin level was significantly increased. The treatment had non-significant effect on body and liver weight. Drug induced hepatotoxicity can be effectively treated with Solanum lycopersicum at 80 mg/kg dose.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Lycopersicon esculentum , Animais , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Isoniazida/toxicidade , Extratos Vegetais/toxicidade , Ratos , Ratos Wistar , Rifampina/toxicidade
14.
J Ethnopharmacol ; 289: 115092, 2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-35143933

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Arctostaphylos uva-ursi (L.) Spreng. (bearberry) is a well-known traditional herbal plant used as a urinary tract disinfectant. Its antiseptic and diuretic properties can be attributed to hydroquinone, obtained by hydrolysis of arbutin. AIM OF THE STUDY: This study aimed to determine the toxic profile of free hydroquinone on urinary bladder cells (T24) as a target of therapeutic action. MATERIALS AND METHODS: Quantitative and qualitative analysis of the extract and the digestive stability and bioavailability of arbutin and hydroquinone were performed by HPLC assay and simulated in vitro digestion, respectively. Cytotoxic effect, reactive oxygen species induction and proteome changes in T24 cells after hydroquinone treatment were determined using Neutral red assay, 2',7'-dichlorofluorescein-diacetate (DCFH-DA) assay and mass spectrometry, respectively. RESULTS: Through in vitro digestion, arbutin was stable, but hydroquinone increased after pepsin treatment (109.6%) and then decreased after the small intestine phase (65.38%). The recommended doses of Uva-ursi had a cytotoxic effect on T24 cells only when all hydroquinone conjugates were converted to free hydroquinone (320 and 900 µg/mL) and the toxic effect was enhanced by recovery. One cup of the therapeutic dose had a prooxidative effect after 4 h of incubation. Shorter time of cell exposure (2 h) to hydroquinone did not have any impact on reactive oxygen species induction. Proteomic analysis found 17 significantly up-regulated proteins compared to control. Hydroquinone activated proteins related to oxidative stress response, stress-adaptive signalling, heat shock response and initiation of translation. CONCLUSIONS: Despite the therapeutic properties of bearberry, up-regulated T24 cell proteins are evidence that plant compounds, although from a natural source, may exhibit negative properties.


Assuntos
Arctostaphylos/química , Hidroquinonas/toxicidade , Extratos Vegetais/toxicidade , Bexiga Urinária/efeitos dos fármacos , Arbutina/química , Arbutina/isolamento & purificação , Células CACO-2 , Linhagem Celular Tumoral , Cromatografia Líquida de Alta Pressão , Humanos , Hidroquinonas/isolamento & purificação , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/química , Proteoma , Proteômica , Bexiga Urinária/citologia
15.
J Ethnopharmacol ; 289: 115090, 2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-35143937

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Tripterygium glycosides tablets (TGT) and Tripterygium wilfordii tablets (TWT) have been used to treat autoimmune diseases clinically, however, the side effects of TWT are higher than TGT, especially for hepatotoxicity. THE AIM OF THE STUDY: This study aims to determine the mechanism of TWT-induced liver injury. MATERIALS AND METHODS: We performed metabolomic analysis of samples from mice with liver injury induced by TGT and TWT. Ppara-null mice were used to determine the role of PPARα in TWT-induced liver injury. RESULTS: The results indicated that TWT induced the accumulation of medium- and long-chain carnitines metabolism, which was associated with the disruption of PPARα-IL6-STAT3 axis. PPARα agonists fenofibrate could reverse the liver injury from TWT and TP/Cel, and its protective role could be attenuated in Ppara-null mice. The toxicity difference of TWT and TGT was due to the different ratio of triptolide (TP) and celastrol (Cel) in the tablet in which TP/Cel was lower in TWT than TGT. The hepatotoxicity induced by TP and Cel also inhibited PPARα and upregulated IL6-STAT3 axis, which could be alleviated following by PPARα activation. CONCLUSIONS: These results indicated that PPARα plays an important role in the hepatotoxicity of Tripterygium wilfordii, and PPARα activation may offer a promising approach to prevent hepatotoxicity induced by the preparations of Tripterygium wilfordii.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/etiologia , PPAR alfa/genética , Extratos Vegetais/toxicidade , Tripterygium/química , Animais , Doença Hepática Induzida por Substâncias e Drogas/genética , Diterpenos/química , Diterpenos/toxicidade , Compostos de Epóxi/química , Compostos de Epóxi/toxicidade , Masculino , Metabolômica , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Triterpenos Pentacíclicos/química , Triterpenos Pentacíclicos/toxicidade , Fenantrenos/química , Fenantrenos/toxicidade , Extratos Vegetais/química , Comprimidos
16.
Fitoterapia ; 157: 105133, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35114336

RESUMO

Six diterpenoids including three ent-kauranes (1-2, 4) and three cleistanthanes (3, 5-6) were isolated from the roots and stems of Phyllanthus acidus (L.) Skeels. Of them, (16S)-ent-16,17,18-tri-hydroxy-19-nor-kaur-4-en-3-one (1), phyllanthone A (2), and 6-hydroxycleistanthol (3) are new compounds, while the ent-kaurane diterpenoids were reported from the titled plant for the first time. Their structures were elucidated on the basis of the extensive spectroscopic analyses. Compounds 2 and 4-6 displayed cytotoxic potential with IC50 values ranging from 1.96 to 29.15 µM. They also showed moderate anti-inflammatory activities (IC50 = 6.30-12.05 µM). Particularly, the new ent-kaurane 2 displayed cytotoxic potential against HL-60 (IC50 = 2.00 µM) and MCF-7 (IC50 = 3.55 µM) cells, and anti-inflammatory activity (IC50 = 6.47 µM).


Assuntos
Diterpenos do Tipo Caurano/toxicidade , Diterpenos/toxicidade , Phyllanthus/química , Extratos Vegetais/toxicidade , Alcaloides/química , Alcaloides/isolamento & purificação , Alcaloides/toxicidade , Linhagem Celular Tumoral , Diterpenos/química , Diterpenos do Tipo Caurano/química , Humanos , Concentração Inibidora 50 , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Extratos Vegetais/síntese química , Raízes de Plantas/química , Caules de Planta/química
17.
J Food Sci ; 87(3): 1319-1330, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35166368

RESUMO

Andrographis paniculata (Burm.f.) Nees (AP) is widely used in most Asian and some Western countries. However, its main effects and underlying pharmacological mechanism have not been thoroughly characterized, and its safety has not been sufficiently investigated. The present study aimed to predict and visualize the potential targets and pathways, clarify the main pharmacological effects, and investigate the toxicological properties of AP extract (APE). First, ingenuity pathway analysis (IPA) was performed to directly predict AP's therapeutic targets and pathways; main pharmacological effects of AP were speculated based on IPA results and confirmed by pharmacodynamics experiments. Rodent toxicity studies were then performed through administration of a single dose of 10 g/kg or daily doses of 2, 1, or 0.5 g/kg for 8 weeks to evaluate the safety of APE, and a similar repeated-dose study was performed using dogs with doses equal to half of the above-mentioned doses. Thus, repeated-dose toxicity studies were performed with both rodents and nonrodents. The IPA analysis and confirmatory pharmacodynamics experiments revealed that the main pharmacological effect of APE was anti-inflammation, which might be achieved by influencing various targets (e.g., AR, AKT, and BAX) and pathways (IL-8). In the single-dose toxicity test, no death or abnormal consequences were observed, and maximum tolerated dose of APE was 10 g/kg. Results from the repeated-dose toxicity tests did not reveal any obvious toxic effects from the repeated daily intragastric administration of APE at 1 g/kg for 8 weeks. In conclusion, APE at a dose of 1 g/kg did not exert any adverse effects, and administration of APE could be beneficial for the inflammatory diseases' treatment. PRACTICAL APPLICATION: Andrographis paniculata (Burm.f.) Nees is a plant that exerts clearing and detoxification effects and is widely used around the world, but a comprehensive analysis of its efficacy and safety is needed.


Assuntos
Andrographis , Animais , Anti-Inflamatórios/farmacologia , Cães , Extratos Vegetais/toxicidade
18.
Molecules ; 27(3)2022 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-35164202

RESUMO

The cause of liver damage by using black cohosh preparation has been concerned but remains unclear. After a preliminary investigation, the black cohosh medicinal materials sold in the market were adulterated with Asian cohosh (Cimicifuga) without removing the fibrous roots. The safety of Cimicifuga rhizome and fibrous roots is unknown and has not been reported. Therefore, in this paper, the rhizome and fibrous roots of Cimicifuga dahurica (Turcz.) Maxim (C. dahurica) were completely separated, extracted with 70% ethanol, and freeze-dried to obtain crude rhizome extract (RC) and fibrous roots extract (FRC). UHPLC-Q-TOF-MS was used to identify 39 compounds in the rhizome and fibrous roots of Cimicifuga, mainly saponins and phenolic acids. In the L-02 cytotoxicity experiment, the IC50 of fibrous roots (1.26 mg/mL) was slightly lower than that of rhizomes (1.417 mg/mL). In the 90-day sub-chronic toxicity study, the FRC group significantly increased the level of white blood cells, ALP, ALT, AST, BILI and CHOL (p < 0.05); large area of granular degeneration and balloon degeneration occurred in liver tissue; and the expression of p-NF-kB in the nucleus increased in a dose-dependent manner. Overall, Fibrous roots of Cimicifuga are at risk of hepatotoxicity and should be strictly controlled and removed during the processing.


Assuntos
Cimicifuga/química , Fígado/efeitos dos fármacos , Extratos Vegetais/toxicidade , Raízes de Plantas/química , Animais , Feminino , Humanos , Masculino , Ratos
19.
J Ethnopharmacol ; 288: 114955, 2022 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-35032590

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Salt-processed Psoraleae fructus (SPF) is widely used as a phytoestrogen-like agent in the treatment of osteoporosis. However, SPF-associated hepatotoxicity is a known health hazard. Cholestasis is often associated with SPF-induced hepatotoxicity. Notably, clinical liver injury is a common side effect of SPF in the treatment of osteoporosis; however, the exact mechanism underlying this phenomenon is unclear. AIM OF THE STUDY: To evaluate SPF-induced hepatotoxicity in an ovariectomized murine model of estrogen deficiency and examine the mechanisms underlying this process. MATERIALS AND METHODS: To explore the molecular mechanism of SPF-induced cholestatic liver injury, different concentrations of SPF (5 and 10 g/kg) were intragastrically administered to ovariectomized and non-ovariectomized female ICR mice for 30 days. RESULTS: SPF-treated mice showed noticeably swollen hepatocytes, dilated bile ducts, and elevated levels of serum biochemical markers. Compared to ovariectomized mice, these changes were more prominent in non-ovariectomized mice. According to the sequence data, a total of 6689 mRNAs were identified. Compared with the control group, 1814 differentially expressed mRNAs were identified in the group treated with high SPF doses (SPHD), including 939 upregulated and 875 downregulated mRNAs. Molecular docking and Western blot experiments showed that liver injury was closely related to the estrogen levels. Compared with the negative control group, the expression levels of FXR, Mrp2, CYP7a1, BSEP, SULT1E1, HNF4a, and Nrf2 decreased in the estradiol-treated (E2), low-dose SPF-treated (SPLD), and SPHD groups. Interestingly, the expression levels of FXR, CYP7a1, SULT1E1, and HNF4α were significantly higher in the ovariectomized groups than in the non-ovariectomized groups (#P < 0.05; ###P < 0.001). CONCLUSIONS: Overall, this study demonstrates that SPF downregulates key enzymes involved in cholesterol and bile acid biosyntheses, posing a risk for cholestatic liver injury. SPF also regulates the FXR-SULT1E signaling pathway via HNF4α, which is an important causative factor of cholestasis. Moreover, the severity of liver damage was significantly lower in the ovariectomized groups than in the non-ovariectomized group. These results suggest that the estrogen level is the most critical factor determining liver injury.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/etiologia , Colestase/induzido quimicamente , Extratos Vegetais/toxicidade , Psoralea/química , Animais , Ácidos e Sais Biliares/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Colestase/patologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Estrogênios/deficiência , Feminino , Frutas , Hepatócitos/efeitos dos fármacos , Hepatócitos/patologia , Camundongos , Camundongos Endogâmicos ICR , Simulação de Acoplamento Molecular , Ovariectomia , Gravidade do Paciente , Extratos Vegetais/administração & dosagem , Sais , Transcrição Genética
20.
BMC Complement Med Ther ; 22(1): 16, 2022 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-35031035

RESUMO

BACKGROUND: Several local communities in Central, Western, Eastern, and Northern regions of Uganda have been using the whole leaf extracts of Aloe vera (L.) Burm. f. (Asphodelaceae) in the treatment of various ailments. Also, several commercial companies sell A. vera as soft drinks in Uganda. However, there are inadequate reports on the toxicities of such preparations. This paper reports the acute and sub-acute oral toxicity of aqueous extracts of whole leaf and green rind of A. vera in Wistar rats. METHODS: Acute oral toxicity test was carried out in female Wistar rats at doses of 175, 550, 1750, and 5000 mg/kg, p.o. The animals were observed for signs of toxicity for 14 days. Similarly, a sub-acute oral toxicity test was performed in both sexes of rats at doses of 200, 400, and 800 mg/kg, p.o. daily for 28 days. All the groups of animals were monitored for behavioral, morphological, biochemical, and physiological changes, including mortality and compared with respective controls. Body weights were measured weekly while the animals' relative organ weights, hematological, biochemical, gross, and microscopic pathology were examined on day 29. RESULTS: There was no mortality or apparent behavioral changes at the doses tested in acute and sub-acute oral toxicity tests. Thus, the Median Lethal Dose (LD50) of green rind and whole leaf aqueous extracts was above 5000 mg/kg. Gross anatomy revealed that the rats' relative spleen weight in green rind extract at 200 mg/kg significantly decreased compared to the control group. The creatinine levels in female rats that received green rind extract and the chloride ion levels in male rats administered whole leaf extract were significantly elevated. Conversely, Mean Corpuscular Hemoglobin Concentration (MCHC) levels significantly decreased at lower doses of the green rind extract compared to the control. Histopathology of the kidney revealed the renal interstitium's inflammation at doses of 200 and 800 mg/kg of the whole leaf extract. CONCLUSION: The findings demonstrated that A. vera green rind and whole leaf extracts are non-toxic at relatively high doses when used for a short duration. Prolonged use of the aqueous whole leaf extract might be associated with kidney toxicity.


Assuntos
Aloe/toxicidade , Extratos Vegetais/toxicidade , Animais , Feminino , Dose Letal Mediana , Masculino , Ratos , Ratos Wistar , Testes de Toxicidade Aguda , Testes de Toxicidade Subaguda , Uganda
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...