RESUMO
In clinic, both synthetic drugs and Shenzhu Capsule (SZC), one kind of traditional Chinese medicines (TCMs), are used to treat ulcerative colitis (UC). In our study, a systems pharmacology approach was employed to elucidate the chemical and mechanism differences between SZC and synthetic drugs in treating UC. First, the compound databases were constructed for SZC and synthetic drugs. Then, the targets of SZC were predicted with on-line tools and validated using molecular docking method. Finally, chemical space, targets, and pathways of SZC and synthetic drugs were compared. Results showed that atractylenolide I, atractylone, kaempferol, etc., were bioactive compounds of SZC. Comparison of SZC and synthetic drugs showed that (1) in chemical space, the area of SZC encompasses the area of synthetic drugs; (2) SZC can act on more targets and pathways than synthetic drugs; (3) SZC can not only regulate immune and inflammatory reactions but also act on ulcerative colitis complications (bloody diarrhea) and prevent UC to develop into colorectal cancer whereas synthetic drugs mainly regulate immune and inflammatory reactions. Our study could help us to understand the compound and mechanism differences between TCM and synthetic drugs.
Assuntos
Colite Ulcerativa/tratamento farmacológico , Medicamentos de Ervas Chinesas/química , Medicina Tradicional Chinesa , Atractilosídeo/química , Cápsulas/química , Cápsulas/uso terapêutico , Colite Ulcerativa/patologia , Medicamentos de Ervas Chinesas/síntese química , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Quempferóis/química , Lactonas/química , Simulação de Acoplamento Molecular , Farmacologia , Sesquiterpenos/químicaRESUMO
The dried ripe fruits of Xanthium sibiricum (Cang'erzi) are used in traditional Chinese medicine for the treatment of nasal congestion, nasal discharge, allergic rhinitis, sinusitis, and wind-cold headaches. Carboxyatractyloside and atractyloside are important constituents of the fruits because these diterpenoid glycosides are responsible for their toxicity. In order to evaluate procedures for reducing the amount of the more toxic carboxyatractyloside, the fruits were dried and heated with different methods. Carboxyatractyloside and atractyloside were analysed by a new reversed-phase high-performance liquid chromatographic method using liquid chromatography-diode array detector-tandem mass spectrometry analysis. The results revealed that temperature and drying methods have a strong influence on the content of carboxyatractyloside and atractyloside. Fruits which were treated at higher temperatures showed a lower content of carboxyatractyloside and an increased content of atractyloside, which is 50 times less toxic. This indicates that the roasting process can reduce toxicity effectively. The microbiological colonisation of Xanthium fruits is also reduced by roasting and by drying above 100â°C. For the safe use of Cang'erzi, the effect of processing should be monitored and analysis of carboxyatractyloside and atractyloside should be obligatory in quality control.
Assuntos
Atractilosídeo/análogos & derivados , Medicamentos de Ervas Chinesas/química , Xanthium/química , Atractilosídeo/química , Atractilosídeo/isolamento & purificação , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia em Camada Fina , Diterpenos , Frutas/química , Frutas/microbiologia , Glicosídeos/química , Glicosídeos/isolamento & purificação , Medicina Tradicional Chinesa , Estrutura Molecular , Xanthium/microbiologiaRESUMO
Xanthium strumarium, commonly referred to as "cocklebur," rarely causes poisoning in cattle. When mature, this robust, annual weed bears numerous oval, brownish, spiny burs. Only the seeds in the burs and young seedlings (cotyledonary leaves) contain the toxic principle, carboxyatractyloside. In the Frankfort district of the Free State Province of South Africa, a herd of 150 Bonsmara cows were allowed to graze on the banks of a small river, where mature cocklebur was growing. Four cows died while grazing in this relatively small area. Clinical signs ranged from recumbency, apparent blindness, and hypersensitivity to convulsive seizures. During necropsy, burs completely matted with ingesta were located in the rumen content. The most distinctive microscopic lesions were severe, bridging centrilobular to midzonal hepatocyte necrosis and hemorrhage. Ultrastructurally, periacinar hepatocytes were necrotic, and novel electron-dense cytoplasmic needle-like crystals were observed, often in close association with peroxisomes. Carboxyatractyloside concentrations were determined using liquid chromatography-high-resolution mass spectrometry (LC-HRMS). Carboxyatractyloside was present in rumen contents at 2.5 mg/kg; in burs removed from the rumen at 0.17 mg/kg; in liver at 66 ng/g, and was below the limit of quantitation in the kidney sample, estimated at approximately 0.8 ng/g. Based on the presence of the plants on the riverbank, the history of exposure, the clinical findings, the presence of burs in the rumen, and the microscopic and ultrastructural lesions, X. strumarium poisoning in the herd of cattle was confirmed and was supported by LC-HRMS.
Assuntos
Atractilosídeo/análogos & derivados , Doenças dos Bovinos/induzido quimicamente , Plantas Tóxicas/intoxicação , Xanthium/intoxicação , Animais , Atractilosídeo/química , Atractilosídeo/intoxicação , Atractilosídeo/toxicidade , Bovinos , Doenças dos Bovinos/epidemiologia , Doenças dos Bovinos/patologia , Feminino , Conteúdo Gastrointestinal/química , Rim/patologia , Fígado/patologia , Necrose/patologia , Rúmen , Sementes/química , África do Sul/epidemiologiaRESUMO
Atractyloside (ATR) is found in many Asteraceae plants that are commonly used as medicinal herbs in China and other eastern Asian countries. ATR binds specifically to the adenine nucleotide translocator in the inner mitochondrial membrane and competitively inhibits ADP and ATP transport. The toxicity of ATR in medical herbs can be reduced by hydrothermal processing, but the mechanisms of ATR degradation are not well understood. In this study, GC-MS coupled with SPE and TMS derivatisation was used to detect ATR levels in traditional Chinese medicinal herbs. Our results suggest that ATR molecules were disrupted by decomposition, hydrolysis and saponification after heating with water (decoction) for a long period of time. Hydrothermal processing could decompose the endogenous toxic compounds and also facilitate the detoxification of raw materials used in the Chinese medicine industry.
Assuntos
Atractilosídeo/química , Atractilosídeo/toxicidade , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/toxicidade , Extratos Vegetais/química , Morte Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Hidrólise/efeitos dos fármacos , Espectrometria de Massas , Padrões de Referência , Temperatura , Água/químicaRESUMO
Atractylis gummifera L. (Asteraceae) is a thistle located in the Mediterranean regions. Despite the plant's well-known toxicity, its ingestion continues to be a common cause of poisoning. The toxicity of Atractylis gummifera resides in atractyloside and carboxyatractyloside, two diterpenoid glucosides capable of inhibiting mitochondrial oxidative phosphorylation. Both constituents interact with a mitochondrial protein, the adenine nucleotide translocator, responsible for the ATP/ADP antiport and involved in mitochondrial membrane permeabilization. Poisoned patients manifest characteristic symptoms such as nausea, vomiting, epigastric and abdominal pain, diarrhoea, anxiety, headache and convulsions, often followed by coma. No specific pharmacological treatment for Atractylis gummifera intoxication is yet available and all the current therapeutic approaches are only symptomatic. In vitro experiments showed that some compounds such as verapamil, or dithiothreitol could protect against the toxic effects of atractyloside, but only if administered before atractyloside exposure. New therapeutic approaches could come from immunotherapy research: some studies have already tried to produce polyclonal Fab fragments against the toxic components of Atractylis gummifera.
Assuntos
Atractylis , Atractilosídeo , Atractilosídeo/análogos & derivados , Inibidores Enzimáticos , Intoxicação , Atractylis/química , Atractylis/intoxicação , Atractilosídeo/química , Atractilosídeo/isolamento & purificação , Atractilosídeo/toxicidade , Criança , Pré-Escolar , Inibidores Enzimáticos/química , Inibidores Enzimáticos/isolamento & purificação , Inibidores Enzimáticos/toxicidade , Etnofarmacologia , Humanos , Região do Mediterrâneo , Intoxicação/mortalidade , Intoxicação/fisiopatologia , Intoxicação/terapiaRESUMO
Atractyloside poisoning is an infrequent but often fatal form of herbal poisoning, which occurs worldwide but especially in Africa and the Mediterranean regions. The primary mechanism of atractyloside poisoning is known to be inhibition of the mitochondrial ADP transporter. Poisoning in humans may present with either acute hepatic or renal pathology and it is possible that there is a second, different mechanism of toxicity to the hepatocyte. Atractyloside in large amounts gives rise to massive necrosis, but in vitro studies have shown that at lower doses cells progress to apoptosis. Simple methods for the detection of atractyloside poisoning are at present restricted to thin-layer chromatography in urine and are useful only in the case of severe poisoning. Immunoassays, high-performance liquid chromatography, nuclear magnetic resonance, and a recently developed high-performance liquid chromatography/mass spectrometry method have yet to be applied to clinical diagnoses. There is at present no treatment, but a fuller understanding of the mechanisms of toxicity may lead to the application of a number of compounds that are effective in vitro.