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1.
Toxicon ; 237: 107550, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38061671

RESUMO

Malpighia emarginata has a high amount of vitamin C with pharmacological or food preservation potential. However, despite its wide use and application possibilities its toxicity in repeated doses and for a long time (6 months) has not yet been studied. In this context, this study aimed to evaluate the acute toxicity and repeated doses from fruits of this plant. The extract was produced with the pulp (EMe) of the lyophilized fruit and submitted to chromatographic and spectroscopic analysis (HPLC and ESI-IT-MSn). In the acute test, the EMe was administered orally and parenterally to rodents (mice and rats) for 14 days, at a dose of 2000 mg/kg. Subsequently, the repeated dose toxicity test was administered orally for 180 days at doses of 50, 300 or 1000 mg/kg. The HPLC assay revealed a high concentration of vitamin C (16.3%), and spectroscopic analyses pointed to the presence of five other polyphenolic compounds. In the acute test, the plant extract showed no apparent toxicity or lethality in rodents. The LD50 was estimated to be greater than 2000 mg/kg and falls into category 5 (low toxicity). In the repeated dose assay, there was no evidence of toxicity, and no differences were observed in water intake, food, weight development, or behavior of the animals in relation to the vehicle group (water). However, hematological and biochemical evaluations pointed out some nonconformities in the levels of cholesterol, leukocytes, and neutrophils of the male rats, but overall, these results did not reveal significant toxicity. Therefore, the Level of Unobserved Adverse Effects (NOAEL) was 1000 mg/kg. Together, the results suggest that the extract obtained from the fruits of M. emarginata does not present representative toxicity in rodents.


Assuntos
Frutas , Roedores , Ratos , Camundongos , Animais , Frutas/toxicidade , Frutas/química , Ácido Ascórbico , Rutina , Extratos Vegetais , Água , Testes de Toxicidade Aguda
2.
Histol Histopathol ; 38(9): 989-997, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36896890

RESUMO

AIMS: Pancreatic adenocarcinoma represents a therapeutic challenge due to the high toxicity of antineoplastic treatments and secondary effects of pancreatectomy. T-514, a toxin isolated from Karwinskia humboldtiana (Kh) has shown antineoplastic activity on cell lines. In acute intoxication with Kh, we reported apoptosis on the exocrine portion of pancreas. One of the mechanisms of antineoplastic agents is the induction of apoptosis, therefore our main objective was to evidence structural and functional integrity of the islets of Langerhans after the administration of Kh fruit in Wistar rats. METHODS: TUNEL assay and immunolabelling against activated caspase-3 were used to detect apoptosis. Also, immunohistochemical tests were performed to search for glucagon and insulin. Serum amylase enzyme activity was also quantified as a molecular marker of pancreatic damage. RESULTS: Evidence of toxicity on the exocrine portion, by positivity in the TUNEL assay and activated caspase-3, was found. On the contrary, the endocrine portion remained structurally and functionally intact, without apoptosis, and presenting positivity in the identification of glucagon and insulin. CONCLUSIONS: These results demonstrated that Kh fruit induces selective toxicity on the exocrine portion and establish a precedent to evaluate T-514 as a potential treatment against pancreatic adenocarcinoma without affecting the islets of Langerhans.


Assuntos
Adenocarcinoma , Ilhotas Pancreáticas , Karwinskia , Neoplasias Pancreáticas , Ratos , Animais , Ratos Wistar , Karwinskia/toxicidade , Caspase 3/metabolismo , Glucagon/metabolismo , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/metabolismo , Frutas/toxicidade , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/metabolismo , Ilhotas Pancreáticas/metabolismo , Insulina , Neoplasias Pancreáticas
3.
Chin J Nat Med ; 20(11): 805-813, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36427915

RESUMO

Psoraleae Fructus (PF) is an important traditional herbal medicine with a long history of clinical application. It is widely used to treat various diseases, such as osteoporosis, leucoderma and diarrhea. As a traditional nontoxic herb, it has aroused worldwide concern about the potential risks due to increasing adverse reaction events. This article reviews the botany, ancient records of medical uses, adverse reactions, toxicological research advance and detoxification methods of PF. According to clinical studies, liver injury is the most predominant in PF-related adverse reactions. The underlying mechanisms include bile acid metabolism and transport disorders, oxidative stress, mitochondrial damage, inhibition of liver cell regeneration and inflammatory reactions. Furthermore, the potential toxins of PF are summarized. Traditional methods of processing and compatibility will provide reference for reducing the toxicity of PF, which requires further research. In sum, this work systematically summarizes the reserach progress on the safety of PF, which will provide comprehensive insights into the toxicity of PF and facilitate its safe use and future development.


Assuntos
Medicamentos de Ervas Chinesas , Medicamentos de Ervas Chinesas/toxicidade , Frutas/toxicidade , Fígado
4.
BMC Complement Med Ther ; 22(1): 178, 2022 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-35787267

RESUMO

BACKGROUND: Tetrapleura tetraptera is a medicinal spice traditionally used to treat cancer, diabetes, and several other ailments. This study analyzed the cytotoxicity of the dichloromethane methanol extract of T. tetraptera fruits (TTF) and its constituents. The toxicity profile of the TTF extract was also evaluated in rats. METHODS: The Cytotoxicity of this extract was evaluated using the resazurin reduction assay (RRA). Acute and sub-chronic toxicity studies were performed according to the protocol described by the Organisation for Economic Cooperation, and Development (OECD). Hematological, serum, and urine biochemical parameters, as well as histological sections of the liver and kidney, were also evaluated based on standard methods. RESULTS: The TTF extract, compound 5, and the reference drug doxorubicin were active in all 9 tested cancer cell lines. The recorded IC50 ranged from 18.32 µM (against B16-F1 murine melanoma cells) to 36.18 µM (against SKMel-505 BRAF wildtype melanoma cells) for TTF, from 10.02 µM (towards MaMel-80a BRAF-V600E homozygous mutant melanoma cells) to 31.73 µM (against SKMel-28 BRAF-V600E homozygous mutant melanoma cells) for compound 5, and from 0.22 µM (against B16-F1 cells) to 9.39 µM (against SKMel-505 cells) for doxorubicin. The study of acute toxicity test showed that the lethal dose (LD50) of this extract was greater than 5000 mg/kg body weight. In the sub-chronic toxicity studies, variations were observed in some biochemical parameters, especially at higher doses. CONCLUSION: TTF and its most active compound (5) are found to be potential cytotoxic agents, meanwhile, TTF was safe when given a single oral dose of 5000 mg/kg. However, caution is necessary in case of prolonged oral administration due to potential alterations of renal function at high doses (> 1000 mg/kg).


Assuntos
Melanoma , Tetrapleura , Animais , Doxorrubicina , Frutas/efeitos adversos , Frutas/toxicidade , Melanoma/tratamento farmacológico , Camundongos , Extratos Vegetais/administração & dosagem , Extratos Vegetais/efeitos adversos , Extratos Vegetais/toxicidade , Proteínas Proto-Oncogênicas B-raf , Ratos , Tetrapleura/efeitos adversos , Tetrapleura/química , Tetrapleura/toxicidade
5.
Drug Chem Toxicol ; 45(3): 1325-1338, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-32962444

RESUMO

Pterodon pubescens Benth. is widely used in folk medicine for the treatment of inflammatory conditions, with the activity attributed to the compounds with a vouacapan moiety, however, few studies report the toxicological evaluation of the extract and safety issues related to the species. Herein the non-clinical toxicity, in in vivo and in vitro tests, of dichloromethane crude extract of Pterodon pubescens fruits (PPE) and vouacapan diterpene furan isomer´s mixture (1:1) 6α-hydroxy-7ß-acetoxy-vouacapan-17ß-oate methyl ester and 6α-acetoxy-7ß-hydroxy-vouacapan-17ß-oate methyl ester isomers (VDFI mixture) is reported. Toxicological evaluation of 110-day repeated dose oral toxicity study, as hematological, biochemical, and histopathological parameters demonstrated that animals (male and female Wistar rats) treated with PPE presented no signs of toxicity, nevertheless daily high dose administration (500 mg/Kg) altered the metabolic homeostasis of animals that manifested microgoticular hepatic steatosis. Biochemical and histopathological results of animals (female Swiss mice) treated daily with VDFI mixture, at the highest dose (300 mg/Kg), indicated liver toxicity in one animal causing acute hepatotoxicity. Alkaline Comet assay demonstrated that PPE and VDFI mixture increased the percentage of DNA fragmentation without interfering with the tail moment parameter, but only VDFI mixture (30 µg/mL) presented statistical difference. In the micronucleus induction test, PPE and VDFI mixture did not demonstrate mutagenic potential. Our data provide evidence for the safety use of PPE and VDFI mixture in lower doses enabling further clinical studies and the development of herbal medicine.


Assuntos
Fabaceae , Frutas , Animais , Ésteres , Fabaceae/química , Fabaceae/toxicidade , Feminino , Frutas/toxicidade , Masculino , Camundongos , Extratos Vegetais/farmacologia , Ratos , Ratos Wistar , Testes de Toxicidade Aguda
6.
Nutrients ; 13(12)2021 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-34959866

RESUMO

Pesticides are widely used in food production, yet the potential harm associated with their emission into the environment is rarely considered in the context of sustainable diets. In this study, a life cycle assessment was used to quantify the freshwater ecotoxicity, human toxicity carcinogenic effects, and human toxicity noncarcinogenic effects associated with pesticide use in relation to 9341 individual Australian adult daily diets. The three environmental indicators were also combined into a pesticide toxicity footprint, and a diet quality score was applied to each diet. Energy-dense and nutrient-poor discretionary foods, fruits, and protein-rich foods were the sources of most of the dietary pesticide impacts. Problematically, a dietary shift toward recommended diets was found to increase the pesticide toxicity footprint compared to the current average diet. Using a quadrant analysis, a recommended diet was identified with a 38% lower pesticide toxicity footprint. This was achieved mainly through a reduction in the discretionary food intake and by limiting the choice of fresh fruits. As the latter contradicts dietary recommendations to eat a variety of fruits of different types and colors, we concluded that dietary change may not be the best approach to lowering the environmental impacts of pesticides in the food system. Instead, targeted action in the horticultural industry may be more effective. Consumers might encourage this transition by supporting growers that reduce pesticide use and apply less environmentally harmful active ingredients.


Assuntos
Dieta/efeitos adversos , Exposição Dietética/análise , Contaminação de Alimentos/análise , Praguicidas/toxicidade , Adulto , Austrália , Dieta/normas , Meio Ambiente , Frutas/toxicidade , Humanos , Recomendações Nutricionais
7.
Artigo em Inglês | MEDLINE | ID: mdl-34800750

RESUMO

Euodiae Fructus (EF), the dried unripe scented fruit of Euodia rutaecarpa (Juss.) Benth., was reported to show anti-hypertensive, antitumor, and anti-obesity effects. The main alkaloids of EF were reported as the reason for toxicity of EF by metabolic activation majority through CYP3A. Up till the present moment, the cytotoxicity mechanisms of EF have not yet to be fully clarified. For the purposes of this article, the influence of CYP3A inducer and inhibitor on cytotoxicity of EF and metabolism in L02 cells of five alkaloids related to toxicity of EF were evaluated. The results indicated that CYP3A inducer aggravated the toxicity and CYP3A inhibitor alleviated the toxicity. UPLC-Q-Exactive-MS was used for the identification of five alkaloids of EF in L02 cells. A total of 13 metabolites were detected in L02 cells. In general, five alkaloids were widely metabolized in L02 cells such as oxygenation, demethylation, dehydrogenation, and etc. In addition, oxygenation was the main metabolic pathway. It was inferred that the toxicity of EF was closely related to the CYP3A and the metabolic intermediate might be one of the reasons for the toxicity of EF. Hence, the choice of optimal dose might be critical to avoid the adverse reactions owing to combination of EF and CYP3A inducer.


Assuntos
Alcaloides/química , Inibidores do Citocromo P-450 CYP3A/toxicidade , Medicamentos de Ervas Chinesas/toxicidade , Evodia/toxicidade , Fígado/efeitos dos fármacos , Alcaloides/metabolismo , Alcaloides/toxicidade , Linhagem Celular , Cromatografia Líquida de Alta Pressão , Citocromo P-450 CYP3A/química , Citocromo P-450 CYP3A/metabolismo , Inibidores do Citocromo P-450 CYP3A/química , Inibidores do Citocromo P-450 CYP3A/metabolismo , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/metabolismo , Evodia/química , Evodia/metabolismo , Frutas/química , Frutas/metabolismo , Frutas/toxicidade , Humanos , Fígado/enzimologia , Espectrometria de Massas
8.
Toxicon ; 203: 1-11, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34600913

RESUMO

In accidental intoxicated animals and humans, Karwinskia humboldtiana (Kh) causes lesions in the central and peripheral nervous system and organs like the kidney, liver, and lung. The objective was to evaluate the histology of myocardium and skeletal muscle after experimental chronic intoxication with mature fruit of Kh in Wistar rat. Twenty-five rats were used and divided into five groups (n = 5): four intoxicated and one control. Kh fruit was ground, dried, sieved, and administered by an orogastric tube. Intoxicated rats received 3.5 g/kg body weight fractionated in 5 doses. Control rats received only water. Animals were euthanized at 24, 48, 58, and 112 days, respectively. Samples of the myocardium and skeletal muscle were obtained and processed for light microscopy evaluation. Morphological analyses were performed, including a microdensitometric analysis. Results showed areas of necrosis in the muscle fibers, fibers with vacuolated cytoplasm, and disorganization of myofilaments, as well as staining variations in both myocardium and skeletal muscle time-depending. Zones with loss of continuity of the external lamina were identified with PAS with the diastase histochemical method. Immunolabeling with specific antibodies demonstrated diminution of actin and desmin myofilaments. The microdensitometric analysis showed a statistically significant difference between the intoxicated vs control group. These findings demonstrate that chronic intoxication of Kh fruit also causes damage in myocardial and skeletal muscle, these alterations will be useful to understand that the toxic effects of Kh fruit in accidently intoxicated humans are systemic, and not only over the nervous system.


Assuntos
Coração/efeitos dos fármacos , Karwinskia , Músculo Esquelético/efeitos dos fármacos , Animais , Frutas/toxicidade , Karwinskia/toxicidade , Músculo Esquelético/patologia , Miocárdio/patologia , Ratos , Ratos Wistar
9.
Phytomedicine ; 90: 153656, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34332844

RESUMO

BACKGROUND: Herb-induced liver injury is a leading cause of drug-induced liver injury in China and its incidence is also increasing worldwide. Gardeniae Fructus (ZZ) has aroused wide concern for hepatotoxicity in recent decades. But when ZZ is administered in combination with Semen Sojae Praeparatum (DDC) to compose a herbal pair Zhizichi Decoction (ZZCD), lower hepatotoxicity is observed. The mechanism involved in the attenuated effect remains to be investigated. HYPOTHESIS/PURPOSE: Our previous studies showed that DDC benefited host metabolism by regulating the gut microbiota and it reduced the exposure of major toxic components of ZZ. The present study was aimed to investigate how DDC attenuated hepatotoxicity of ZZ from the perspective of gut microbiota. METHODS: Rats received ZZ and ZZCD treatment of different dosages and antibiotic treatment was applied to explore the involvement of gut microbiota. Biochemical assays and histopathological analysis were conducted to evaluate liver injury. Gut microbiota in caecal contents was profiled by 16S rRNA sequencing. Short-chain fatty acids (SCFAs) in caecal contents were measured by gas chromatography mass spectrometry (GCMS). To verify the protective effect of butyrate, it was administered with genipin, the major hepatotoxic metabolite of ZZ, to rats and HepG2 cells. Plasma lipopolysaccharide (LPS) level and colon tissue section were used to evaluate gut permeability. Expression level of Nuclear factor erythroid-derived 2-like 2 (Nrf2) was detected by immunohistochemistry in vitro and by western blot in vivo. RESULTS: Our study showed that ZZCD displayed lower hepatotoxicity than ZZ at the same dosage. ZZ induced gut dysbiosis, significantly reducing Lactobacillus and Enterococcus levels and increasing the Parasutterella level. In combination with DDC, these alterations were reversed and beneficial genus including Akkermansia and Prevotella were significantly increased. Besides, butyrate production was diminished by ZZ but was restored when in combination with DDC. Butyrate showed detoxification on genipin-induced liver injury by promoting colon integrity and promoting Nrf2 activation. Besides, it protected genipin-induced hepatocyte damage by promoting Nrf2 activation. CONCLUSION: DDC attenuates ZZ-induced liver injury by regulating the microbiota, promoting butyrate production and activating antioxidant response.


Assuntos
Antioxidantes/metabolismo , Butiratos/metabolismo , Doença Hepática Induzida por Substâncias e Drogas , Gardenia , Microbioma Gastrointestinal , /química , Animais , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Frutas/toxicidade , Gardenia/toxicidade , RNA Ribossômico 16S , Ratos
11.
J Agric Food Chem ; 68(49): 14603-14609, 2020 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-33233889

RESUMO

Ackee fruits (Blighia sapida), an important food source in some tropical countries, can be the cause of serious poisoning. Ackees contain hypoglycin A and methylenecyclopropylglycine. Experiments were undertaken by a volunteer to elucidate the metabolic details of poisoning. Rapid intestinal absorption of the toxins was followed by their slow degradation to methylenecyclopropylacetyl and methylenecyclopropylformyl conjugates. Impairment of the metabolism of branched chain amino acids and ß-oxidation of fatty acids was found. Reduced enzyme activities were observed for several days after ingestion. A defined dose of fruit material caused significantly higher concentrations of metabolites when consumed 24 h after a previous ingestion than when consumed only once. The accumulation of toxins, toxin metabolites, and products of the intermediate metabolism after repeated consumption may, at least partly, explain the high frequency of fatal cases observed during harvesting. No inhibition of enzymes that degrade long-chain acyl compounds was observed in the experiments.


Assuntos
Blighia/metabolismo , Alimentos em Conserva/efeitos adversos , Frutas/toxicidade , Adulto , Blighia/toxicidade , Ciclopropanos/metabolismo , Ciclopropanos/toxicidade , Ácidos Graxos/metabolismo , Feminino , Alimentos em Conserva/análise , Frutas/metabolismo , Glicina/análogos & derivados , Glicina/metabolismo , Glicina/toxicidade , Humanos , Hipoglicinas/metabolismo , Hipoglicinas/toxicidade
12.
Regul Toxicol Pharmacol ; 118: 104785, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32976857

RESUMO

The objective of the present study was to evaluate the safety of standardized 70% ethanolic extract of Benincasa hispida fruit pulp (HABH) in rodents. Chemical characterization of HABH has been done by GC-MS and dimethylsulfoxonium formyl methylide, l-(+)-ascorbic acid and 2,6-dihexadecanoate were identified as major compounds in the extract. Acute oral toxicity study of HABH was done according to the Organization for Economic Cooperation and Development (OECD) guideline, by 'up and down' method, using the limit test at 2000 mg/kg, body weight in mice and were observed up to 14 days. In sub-chronic oral toxicity study, HABH was administered to Wistar rats at doses of 1000, 200 and 40 mg/kg b. w. per day for 90 days. In acute toxicity study, there was no mortality and no behavioural signs of toxicity at the limit test dose level (2000 mg/kg b. w.). In sub-chronic oral toxicity study, there was no significant difference observed in the consumption of food and water, body weight and relative organ weights. Haematological, serum biochemical and urine analysis revealed the non-adverse effects of prolonged oral consumption of HABH. The histopathologic examination did not show any differences in vital organs. Based on our findings, HABH, at dosage levels up to 1000 mg/kg b. w., is non-toxic and safe for long term oral consumption.


Assuntos
Cucurbitaceae/toxicidade , Frutas/toxicidade , Extratos Vegetais/toxicidade , Testes de Toxicidade Aguda , Testes de Toxicidade Subcrônica , Administração Oral , Animais , Comportamento Animal/efeitos dos fármacos , Biomarcadores/sangue , Biomarcadores/urina , Peso Corporal/efeitos dos fármacos , Cucurbitaceae/química , Ingestão de Líquidos/efeitos dos fármacos , Ingestão de Alimentos/efeitos dos fármacos , Feminino , Frutas/química , Dose Letal Mediana , Masculino , Camundongos , Tamanho do Órgão/efeitos dos fármacos , Extratos Vegetais/administração & dosagem , Extratos Vegetais/isolamento & purificação , Ratos Wistar , Medição de Risco , Fatores de Tempo
13.
J Ethnopharmacol ; 263: 113231, 2020 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-32758577

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The fruit of Tetradium ruticarpum (FTR) known as Tetradii fructus or Evodiae fructus (Wu-Zhu-Yu in Chinese) is a versatile herbal medicine which has been prescribed in Chinese herbal formulas and recognized in Japanese Kampo. FTR has been clinically used to treat various diseases such as headache, vomit, diarrhea, abdominal pain, dysmenorrhea and pelvic inflammation for thousands of years. AIM OF THE REVIEW: The present paper aimed to provide comprehensive information on the ethnopharmacology, phytochemistry, pharmacology, pharmacokinetics, drug interaction and toxicology of FTR in order to build up a foundation on the mechanism of ethnopharmacological uses as well as to explore the trends and perspectives for further studies. MATERIALS AND METHODS: This review collected the literatures published prior to July 2020 on the phytochemistry, pharmacology, pharmacokinetics and toxicity of FTR. All relevant information on FTR was gathered from worldwide accepted scientific search engines and databases, including Web of Science, PubMed, Elsevier, ACS, ResearchGate, Google Scholar, and Chinese National Knowledge Infrastructure (CNKI). Information was also obtained from local books, PhD. and MSc. Dissertations as well as from Pharmacopeias. RESULTS: FTR has been used as an herbal medicine for centuries in East Asia. A total of 165 chemical compounds have been isolated so far and the main chemical compounds of FTR include alkaloids, terpenoids, flavonoids, phenolic acids, steroids, and phenylpropanoids. Crude extracts, processed products (medicinal slices) and pure components of FTR exhibit a wide range of pharmacological activities such as antitumor, anti-inflammatory, antibacterial, anti-obesity, antioxidant, insecticide, regulating central nervous system (CNS) homeostasis, cardiovascular protection. Furthermore, bioactive components isolated from FTR can induce drug interaction and hepatic injury. CONCLUSIONS: Therapeutic potential of FTR has been demonstrated with the pharmacological effects on cancer, inflammation, cardiovascular diseases, CNS, bacterial infection and obesity. Pharmacological and pharmacokinetic studies of FTR mostly focus on its main active alkaloids. Further in-depth studies on combined medication and processing approaches mechanisms, pharmacological and toxic effects not limited to the alkaloids, and toxic components of FTR should be designed.


Assuntos
Medicamentos de Ervas Chinesas/toxicidade , Evodia/toxicidade , Frutas/toxicidade , Medicina Tradicional Chinesa/métodos , Compostos Fitoquímicos/toxicidade , Analgésicos/química , Analgésicos/farmacocinética , Analgésicos/toxicidade , Animais , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacocinética , Evodia/química , Frutas/química , Fármacos Gastrointestinais/química , Fármacos Gastrointestinais/farmacocinética , Fármacos Gastrointestinais/toxicidade , Humanos , Medicina Tradicional Chinesa/tendências , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacocinética
14.
J Ethnopharmacol ; 248: 112349, 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-31756450

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Arenga pinnata (Wurmb) Merr. is a medicinal and edible plant belonging to family Palmae. The fruits of this plant were used in traditional folk medicine due to its analgesia and anti-inflammatory activities. This study aimed to investigate the analgesic and anti-inflammatory properties and the mechanism of the ethanol extract of A. pinnata (Wurmb) Merr. fruit (EAF) on different experimental models. MATERIALS AND METHODS: High-performance liquid chromatography (HPLC) was used to determine the chromatographic profile and to analyze the composition of EAF. In the acute toxicity test, all mice were orally administered EAF at a maximum dosage of 26 g/kg and were then monitored for 14 days. The potential analgesic activity of EAF was evaluated by using animal pain models, namely the acetic acid-induced writhing test and the hot plate test in mice. The underlying mechanisms of analgesia were determined by pretreating with naloxone, capsaicin and cinnamaldehyde to evaluate the involvement of the opioid system and transient receptor potential channels (TRP channels). The anti-inflammatory activity of EAF was evaluated by using the following inflammatory animal models: xylene-induced ear edema in mice and Complete Freund's adjuvant (CFA)-induced paw swelling in rats. EAF was orally administered at the doses of 1.625, 3.25 and 6.5 g/kg in mice and 1.125, 2.25 and 4.5 g/kg in rats. The underlying mechanism of the anti-inflammatory activity was determined by enzyme-linked immunosorbent assay (ELISA) kits and real time-PCR used to measure the expression levels of interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), prostaglandin E2 (PGE2) and cyclooxygenase-2 (COX-2). Western blot analysis was used to determine the expression levels of proteins related to the nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPK) signaling pathways in paw tissues. RESULTS: Five compounds, namely (5-(hydroxymethyl) furan-2-yl) methanediol,4'-hydroxy-N-(4-hydroxy-3-methoxybenzoyl)-3',5'-dimethoxybenzamide, (+)-lyonirenisol-3a-O-ß-D-glucopyranoside, (-)-lyonirenisol-3a-O-ß-glucopyranoside and liquiritin, were firstly identified from A. pinnata (Wurmb) Merr. fruit by HPLC-UV analysis. In the acute toxicity test, no treatment-related toxicological signs or mortality was observed in mice administered doses up to 26 g/kg. Bodyweight was not obviously different among the treatment groups and the vehicle group. EAF significantly inhibited the pain response induced by acetic acid and increased the latency time in the hot plate test in mice. The anti-nociception effect of EAF in the formalin test was not alleviated by pretreatment with naloxone. However, the nociception induced by injection with capsaicin and cinnamaldehyde was significantly reduced by EAF. Compared with vehicle treatment, EAF significantly inhibited the formation of xylene-induced ear edema and CFA adjuvant-induced paw swelling. EAF markedly inhibited the production of IL-1ß, TNF-α, PGE2 and IL-6 induced by CFA in paw tissues. Furthermore, the phosphorylation of IKKα, IKKß, IκBα, p38, ERK1/2, and JNK and the nuclear translation of NF-κB p65 induced by CFA in paw tissues were significantly inhibited by EAF treatment compared with vehicle treatment. CONCLUSION: For the first time, this study provides pharmacological evidence for the analgesic and anti-inflammatory activities of EAF and the underlying mechanism, suggesting that EAF might be a potential candidate for reducing pain and inflammatory disorders.


Assuntos
Analgésicos/farmacologia , Anti-Inflamatórios/farmacologia , Arecaceae , Edema/prevenção & controle , Etanol/química , Frutas , Inflamação/prevenção & controle , Dor/prevenção & controle , Extratos Vegetais/farmacologia , Solventes/química , Analgésicos/isolamento & purificação , Analgésicos/toxicidade , Animais , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/toxicidade , Arecaceae/química , Arecaceae/toxicidade , Citocinas/metabolismo , Modelos Animais de Doenças , Edema/metabolismo , Feminino , Frutas/química , Frutas/toxicidade , Inflamação/metabolismo , Mediadores da Inflamação/metabolismo , Masculino , Camundongos Endogâmicos ICR , NF-kappa B/metabolismo , Dor/fisiopatologia , Limiar da Dor/efeitos dos fármacos , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/toxicidade , Ratos Sprague-Dawley
15.
BMC Complement Altern Med ; 19(1): 184, 2019 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-31340810

RESUMO

BACKGROUND: Bitter gourd (Momordica charantia) has attracted the focus of researchers owing to its excellent anti-diabetic action. The beneficial effect of Momordica charantia on heart has been reported by in vitro and in vivo studies. However the developmental toxicity or potential risk of M. charantia on fetus heart development is largely unknown. Hence this study was designed to find out the developmental toxicity of M. charantia using zebrafish (Danio rerio) embryos. METHODS: The crude extracts were prepared from fruit and seeds of M. charantia. The Zebrafish embryos were exposed to serial dilution of each of the crude extract. The biologically active fractions were fractionated by C18 column using high pressure liquid chromatography. Fourier-transform infrared spectroscopy and gas chromatography coupled with mass spectrophotometry was done to identify chemical constituents in fruit and seed extract of M. charantia. RESULTS: The seed extract of M. charantia was lethal with LD50 values of 50 µg/ml to zebrafish embryos and multiple anomalies were observed in zebrafish embryos at sub-lethal concentration. However, the fruit extract was much safe and exposing the zebrafish embryos even to 200 µg/ml did not result any lethality. The fruit extract induced severe cardiac hypertrophy in treated embryos. The time window treatment showed that M. charantia perturbed the cardiac myoblast specification process in treated zebrafish embryos. The Fourier-transform infrared spectroscopy analyses revealed diverse chemical group in the active fruit fraction and five new type of compounds were identified in the crude seeds extract of M. charantia by gas chromatography and mass spectrophotometry. CONCLUSION: The teratogenicity of seeds extract and cardiac toxicity by the fruit extract of M. charantia warned that the supplementation made from the fruit and seeds of M. charantia should be used with much care in pregnant diabetic patients to avoid possible damage to developing fetus.


Assuntos
Momordica charantia/química , Extratos Vegetais/toxicidade , Peixe-Zebra/embriologia , Animais , Feminino , Frutas/química , Frutas/toxicidade , Humanos , Dose Letal Mediana , Masculino , Momordica charantia/toxicidade , Extratos Vegetais/análise , Sementes/química , Sementes/toxicidade
16.
Zhongguo Zhong Yao Za Zhi ; 44(24): 5336-5344, 2019 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-32237377

RESUMO

Xanthii Fructus is a traditional Chinese medicine for the treatment of sinusitis and headache,rich in medicinal materials and is widely used for more than 1 800 years. Modern pharmacological studies have showed that Xanthii Fructus has anti-inflammatory,analgesic,anti-tumor,anti-bacterial,hypoglycemic,anti-allergic,immunomodulatory and other pharmacological effects,which can be commonly used in the treatment of diseases relating to immune abnormalities,such as rheumatoid arthritis,acute and chronic rhinitis,allergic rhinitis,and skin diseases,with a high medicinal value. Toxicological studies have shown that Xanthii Fructus poisoning can cause substantial damage to organs,such as the liver,kidney,and gastrointestinal tract,especially to liver. Because of the coexisting of its efficacy and toxicity,Xanthii Fructus often leads to a series of safety problems in the clinical application process. This study attempts to summarize its characteristics of adverse reactions,analyze the root cause of the toxicity of Xanthii Fructus from such aspects as processing,dose,course of treatment and eating by mistake,discuss the substance of its efficacy/toxicity from chemical compositions,and put forward exploratory thinking about how to promote its clinical rational application from the aspects such as strict processing,reasonable compatibility,medication information,contraindication,strict control of the dose,and course of treatment,so as to promote the safe and reasonable application of Xanthii Fructus.


Assuntos
Medicamentos de Ervas Chinesas/efeitos adversos , Frutas/toxicidade , Xanthium/toxicidade , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Medicina Tradicional Chinesa
17.
Nat Prod Res ; 33(16): 2379-2382, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29468897

RESUMO

Plant extracts can provide a viable alternative to controlling many crop pests. This study sought to assess the efficacy of vegetable extracts of the unripe fruits of Ilex paraguariensis (yerba maté) for chemical control of the channeled apple snail (Pomacea canaliculata) and of non-target species as the South American catfish (Rhamdia quelen) under laboratory conditions. In P. canaliculata, the LC50 of the decoction extract was 31.39 mg.L-1 and the LT50 was over 26 h. The LC50 of the butanol extract was 24.75 mg.L-1 and the LT50 was in the range of 28 to 32 h. In juvenile R. quelen, the LC50 of the decoction was 17.98 mg.L-1 and the LT50 was in the range of 10-12 h. These extracts are particularly attractive considering the source of compounds and their effectiveness as molluscicides.


Assuntos
Agentes de Controle Biológico/toxicidade , Frutas/toxicidade , Ilex paraguariensis/química , Extratos Vegetais/toxicidade , Caramujos/efeitos dos fármacos , Animais , Agentes de Controle Biológico/química , Agentes de Controle Biológico/isolamento & purificação , Peixes-Gato , Frutas/química , Dose Letal Mediana , Extratos Vegetais/química , Solventes
18.
Crit Rev Food Sci Nutr ; 59(10): 1580-1604, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-29360387

RESUMO

The term "superfruit" has gained increasing usage and attention recently with the marketing strategy to promote the extraordinary health benefits of some exotic fruits, which may not have worldwide popularity. This has led to many studies with the identification and quantification of various groups of phytochemicals. This contribution discusses phytochemical compositions, antioxidant efficacies, and potential health benefits of the main superfruits such as açai, acerola, camu-camu, goji berry, jaboticaba, jambolão, maqui, noni, and pitanga. Novel product formulations, safety aspects, and future perspectives of these superfruits have also been covered. Research findings from the existing literature published within the last 10 years have been compiled and summarized. These superfruits having numerous phytochemicals (phenolic acids, flavonoids, proanthocyanidins, iridoids, coumarins, hydrolysable tannins, carotenoids, and anthocyanins) together with their corresponding antioxidant activities, have increasingly been utilized. Hence, these superfruits can be considered as a valuable source of functional foods due to the phytochemical compositions and their corresponding antioxidant activities. The phytochemicals from superfruits are bioaccessible and bioavailable in humans with promising health benefits. More well-designed human explorative studies are needed to validate the health benefits of these superfruits.


Assuntos
Antioxidantes/farmacologia , Frutas/química , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/farmacologia , Antocianinas/análise , Antioxidantes/análise , Carotenoides/análise , Cumarínicos/análise , Flavonoides/análise , Frutas/toxicidade , Alimento Funcional/análise , Humanos , Taninos Hidrolisáveis/análise , Hidroxibenzoatos/análise , Iridoides/análise , Fenóis/análise , Compostos Fitoquímicos/análise , Proantocianidinas/análise
19.
Biomed Environ Sci ; 32(11): 839-853, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31910941

RESUMO

OBJECTIVE: This study was conducted to evaluate the concentration of potentially toxic elements (PTEs) such as arsenic (As), cadmium (Cd), mercury (Hg), and lead (Pb) in fruit samples collected from Markazi Province, Iran. A probabilistic health risk assessment due to ingestion of PTEs through the consumption of these fruits was also conducted. METHODS: The concentration of PTEs in 90 samples of five types of fruits (n = 3) collected from six geographic regions in Markazi Province was measured. The potential health risk was evaluated using a Monte Carlo simulation model. RESULTS: A significant difference was observed in the concentration of PTEs between fruits as well as soil and water samples collected from different regions in Markazi Province. The order of PTE concentration in the soil and water samples was as follows: Pb > As > Hg > Cd. Furthermore, the highest level of transfer factor for Cd and Hg correlated with the grape. The estimated daily intake for adults and children was lower than the recommended tolerable daily intake. CONCLUSION: The population in Markazi Province, Iran, is not at considerable noncarcinogenic or carcinogenic risk due to the ingestion of PTEs through the consumption of the examined fruits.


Assuntos
Frutas/química , Adolescente , Adulto , Arsênio/análise , Arsênio/metabolismo , Arsênio/toxicidade , Cádmio/análise , Cádmio/metabolismo , Cádmio/toxicidade , Ingestão de Alimentos , Feminino , Contaminação de Alimentos/análise , Frutas/metabolismo , Frutas/toxicidade , Humanos , Irã (Geográfico) , Chumbo/análise , Chumbo/metabolismo , Chumbo/toxicidade , Masculino , Mercúrio/análise , Mercúrio/metabolismo , Mercúrio/toxicidade , Pessoa de Meia-Idade , Medição de Risco , Adulto Jovem
20.
Molecules ; 23(11)2018 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-30380729

RESUMO

The effect of the addition of ionic liquids (ILs) during the hydrodistillation of Myristica fragrans Houtt. (nutmeg) essential oil was studied. The essential oil of M. fragrans is characterized by the presence of terpenes, terpenoids, and of phenylpropanoids, such as methyl eugenol and safrole, that are regarded as genotoxic and carcinogenic. The aim of the work was to determine the best ionic liquid to improve the yield of the extraction of M. fragrans essential oil and decrease the extraction of toxic phenylpropanoids. Six ILs, namely 1,3-dimethylimidazolium chloride (1), 1,3-dimethylimidazolium dimethylphosphate (2), 1-(2-hydroxyethyl)-3-methylimidazolium chloride (3), 1-(2-hydroxyethyl)-3-methylimidazolium dimethylphosphate (4), 1-butyl-3-methylimidazolium chloride (5), and 1-butyl-3-methylimidazolium dimethylphosphate (6), were prepared by previously reported, innovative methods and then tested. An experimental design was used to optimize the extraction yield and to decrease the phenylpropanoids percentage using the synthesized ILs. The influence of the molarity of ILs was also studied. MODDE 12 software established 0.5 M 1-butyl-3-methylimidazolium chloride as the best co-solvent for the hydrodistillation of M. fragrans essential oil.


Assuntos
Imidazóis/farmacologia , Líquidos Iônicos/farmacologia , Myristica/química , Óleos Voláteis/química , Frutas/química , Frutas/efeitos dos fármacos , Frutas/toxicidade , Cromatografia Gasosa-Espectrometria de Massas , Imidazóis/química , Líquidos Iônicos/química , Myristica/efeitos dos fármacos , Myristica/toxicidade , Óleos Voláteis/toxicidade , Sementes/química
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