RESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: 25 flavors of the turquoise pill, a traditional Tibetan medicine for the treatment of various types of hepatitis, has not been investigated on its safety, especially the component mineral turquoise, which is believed to be essential but worried for its potential toxicity. AIM OF THE STUDY: To explore the potential acute toxicity and function of 25 flavors of the turquoise pill and turquoise, the possible mechanism of the effects of turquoise and 25 flavors of the turquoise pill were systematically studied based on 1H NMR metabolomics. MATERIALS AND METHODS: The rats were administered with turquoise and 25 flavors of the turquoise pill by gavage for 7 days, and samples of serum, liver, and kidney were collected. The potential toxicity and function of turquoise and 25 flavors of the turquoise pill on the liver and kidney of SD rats were evaluated by 1H NMR metabonomics, histopathology, and biochemical indexes. RESULTS: The results demonstrated that 25 flavors of the turquoise pill could scavenge free oxygen radicals, strengthen aerobic respiration and inhibit glycolysis in the liver. It did not cause oxidative stress in the kidney with no obvious damage. By modulation of branched-chain amino acids (BCAAs), 25 flavors of the turquoise pill can improve the utilization of glucose and promote aerobic respiration of the kidney. CONCLUSION: Considering the high dosage and short duration used in this study relative to their typical clinical usage, administration of 25 flavors of the turquoise pill and its component mineral turquoise are safe to livers and kidneys.
Assuntos
Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Medicina Tradicional Tibetana/efeitos adversos , Minerais/toxicidade , Animais , Relação Dose-Resposta a Droga , Aromatizantes/química , Sequestradores de Radicais Livres/isolamento & purificação , Sequestradores de Radicais Livres/farmacologia , Glucose/metabolismo , Rim/metabolismo , Fígado/metabolismo , Espectroscopia de Ressonância Magnética , Masculino , Medicina Tradicional Tibetana/métodos , Metabolômica , Minerais/isolamento & purificação , Minerais/farmacologia , Ratos Sprague-Dawley , Medição de Risco , Testes de Toxicidade AgudaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Wu-Zi-Yan-Zong-Wan (WZYZW) is a commonly used Chinese medicinal recipe for oligozoospermia. Oligozoospermia is a common disease that harms human fertility, there is no effective therapeutic medicine at present. However, the underlying pharmacological mechanism remains unclear. METHODS: Oligozoospermia rats model induced by Tripterygium glycosides (TG) was established to inspect the efficiency of WZYZW in the treatment of oligozoospermia by traditional pharmacodynamics combined with NMR-based metabolomics. Multivariate statistics were used to extracted the underlying biomarkers and metabolic pathways of WZYZW in the treatment of oligozoospermia. RESULTS: The results showed that TG disturbed many metabolites and metabolic pathways such as oxidative stress (choline, O-phosphocholine, betaine and ascorbate), energy metabolism in mitochondria (glucose, lactate, succinate, fumarate, 3-hydroxybutyrate and alanine), mitochondrial apoptosis markers (Bax and Bcl-2) and amino acids metabolisms (arginine, branched-chain amino acids, taurine and myo-inositol). CONCLUSIONS: WZYZW could significantly reverse the disturbed metabolites to their normal status by their abilities of anti-oxidation, anti-apoptosis, balancing the osmotic pressure regulatory molecules and regulating the amino acids metabolism. This study provides pharmacological basis and guidance for the clinical usage of WZYZW.
Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Metabolômica , Oligospermia/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Aminoácidos/metabolismo , Animais , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Biomarcadores/metabolismo , Diterpenos , Compostos de Epóxi , Espectroscopia de Ressonância Magnética , Masculino , Oligospermia/metabolismo , Pressão Osmótica/efeitos dos fármacos , Fenantrenos , Ratos , Ratos Sprague-DawleyRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Gastrodiae Rhizoma (GR), a well-known and commonly-used TCM (Traditional Chinese Medicine) for treating headache, dizziness, tetanus, epilepsy, and etc., has been proven to relieve chronic atrophic gastritis (CAG). Due to its complex ingredients, the active fractions responsible for the treatment of CAG remain largely unknown. AIM OF THE STUDY: To explore the underlying material and interpret its underlying mechanism, the therapeutic effect of extract from different polar parts of Gastrodiae Rhizoma on autoimmune CAG was studied based on the 1H NMR metabolomics. MATERIALS AND METHODS: The rat model of CAG was established by autoimmune method. The modeled CAG rats were then treated with 4 polar parts (T1-4 in descending polarity, corresponding to water, n-butanol, ethyl acetate and petroleum ether extracts, respectively) of Gastrodiae Rhizoma for 21 consecutive days. The stomach and serum samples were collected and then subjected to histopathology observation, biochemical measurement (MDA, SOD, GSH, NO, XOD and pepsin), 1H NMR metabolic profiling and multivariate/univariate statistical analysis. RESULTS: The results showed that T1 had the best therapeutic effect, T2 the second, and T3 and T4 the poorest with no obvious therapeutic effect, demonstrating that the effective components of Gastrodiae Rhizoma should be compounds of high polarity. T1 achieved good therapeutic effects due to the anti-inflammatory and anti-oxidant activities, and by rectifying the disturbed energy and amino acid metabolism in CAG model. CONCLUSION: This integrated metabolomics approach proved the validity of the therapeutic effect of extract from different polar parts of Gastrodiae Rhizoma on autoimmune CAG, providing new insights into the underlying mechanisms, and demonstrating the feasibility of metabolomics to evaluate efficacy of herbal drug, which is often difficult by traditional means.
Assuntos
Gastrite Atrófica/prevenção & controle , Gastrodia/química , Metabolômica , Extratos Vegetais/farmacologia , Animais , Interações Hidrofóbicas e Hidrofílicas , Masculino , Extratos Vegetais/química , Espectroscopia de Prótons por Ressonância Magnética , Ratos , Rizoma/química , Solventes/químicaRESUMO
The Herpetospermum caudigerum Wall (HCW) is a traditional Tibetan medicine and is widely used in clinical practice. However, the shell of the HCW (SHCW) has rarely been studied, and some researchers have suggested that the SHCW may be toxic. Therefore, in this study, SHCW was administered to rats at two doses (0.1 and 0.33â¯g/kg) once a day for 21 days. The hepatic stimuli induced by SHCW in rats were investigated for the first time by 1H-NMR-based metabolomics combined with histopathological observation and biochemical detection. Histopathological sections showed a certain degree of hepatocyte edema and hepatic sinus congestion in the liver tissue of the rats in the drug-administered group. Serum biochemical indicators revealed a significant increase in ALT, AST, and MDA, and a significant decrease in SOD. Metabolomic results showed that the metabolites in rats were changed after gavage administration of extracts from SHCW. By multivariate statistical analysis and univariate analysis, it was found that SHCW could cause the disorder of energy metabolism, oxidative stress and amino acid metabolism in rats, leading to liver damage. This comprehensive metabolomics approach demonstrates its ability to describe the global metabolic state of an organism and provides a powerful and viable tool for exploring drug-induced toxicity or side effects.
Assuntos
Doença Hepática Induzida por Substâncias e Drogas/diagnóstico , Cucurbitaceae/toxicidade , Medicina Tradicional Tibetana/efeitos adversos , Metabolômica/métodos , Extratos Vegetais/toxicidade , Espectroscopia de Prótons por Ressonância Magnética , Animais , Biomarcadores/sangue , Biomarcadores/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Modelos Animais de Doenças , Etanol/química , Humanos , Testes de Função Hepática/métodos , Masculino , Extratos Vegetais/isolamento & purificação , RatosRESUMO
Chronic atrophic gastritis (CAG) is one of the most common digestive system diseases worldwide which defined by WHO as initial step of cancer. Gastrodia elata Blume (GEB) is a traditional herbal with multiple pharmacological activities which was widely used in Asian countries. This study aims to explore the preventive and therapeutical effects of Gastrodia elata Blume on auto-immune induced CAG in rats. Tissues of stomachs were collected and submitted to 1H NMR-based metabolomics analysis and histopathological inspection. The biochemical indexes of MDA, SOD, GSH, NO and XOD were measured. Gastrodia elata Blume could apparently ameliorate the damaged gastric glands and the biochemical parameters, enhance gastric acid secretion, and significantly relieve the inflammation of the stomach. Orthogonal signal correction-partial least squares-discriminant analysis (OSC-PLS-DA) of NMR profiles and correlation network analysis revealed that Gastrodia elata Blume could effectively treat CAG via regulating energy and purine metabolisms, and by anti-oxidation and anti-inflammation effects.
Assuntos
Gastrite Atrófica/prevenção & controle , Gastrodia/química , Espectroscopia de Ressonância Magnética/métodos , Metabolômica/métodos , Extratos Vegetais/uso terapêutico , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Modelos Animais de Doenças , Metabolismo Energético/efeitos dos fármacos , Ácido Gástrico/metabolismo , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Gastrite Atrófica/tratamento farmacológico , Gastrite Atrófica/imunologia , Gastrite Atrófica/metabolismo , Humanos , Espectroscopia de Ressonância Magnética/instrumentação , Masculino , Metabolômica/instrumentação , Extratos Vegetais/farmacologia , Purinas/metabolismo , Ratos , Ratos Sprague-DawleyRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Herpetospermum caudigerum Wall. (HCW) is a traditional Tibetan medicine, which has been used to ameliorate liver injuries in the folk. AIM OF THE STUDY: Liver fibrosis has been recognized as a major lesion of the liver that leads to liver cirrhosis/hepatocarcinoma and even to death in the end. This study aims to demonstrate the protective effect of HCW against CCl4-induced liver injury in rats and to explore the underlying mechanisms. MATERIALS AND METHODS: Hepatic fibrosis was induced by intraperitoneal injection of CCl4. Liver function markers, fibrosis markers, serum anti-oxidation enzymes as well as elements levels were determined. Serum and liver tissues were subjected to NMR-based metabolomics and multivariate statistical analysis. RESULTS: HCW could significantly reduce the elevated levels of fibrosis markers such as hyaluronidase, laminin, Type III procollagen and Type IV collagen in the serum, improve the activities of the antioxidant enzymes, and effectively reverse the abnormal levels of elements in liver fibrosis rats. Correlation network analysis revealed that HCW could treat liver fibrosis by ameliorating oxidative stress, repairing the impaired energy metabolisms and reversing the disturbed amino acids and nucleic acids metabolisms. CONCLUSION: This integrated metabolomics approach confirmed the validity of the traditional use of HCW in the treatment of liber fibrosis, providing new insights into the underlying mechanisms.
Assuntos
Cucurbitaceae , Cirrose Hepática/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Substâncias Protetoras/uso terapêutico , Animais , Tetracloreto de Carbono , Metabolismo Energético/efeitos dos fármacos , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/metabolismo , Masculino , Estresse Oxidativo/efeitos dos fármacos , Fitoterapia , Ratos Sprague-Dawley , SementesRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Polygonum multiflorum Thund., a well-known and commonly-used TCM (Traditional Chinese Medicine) for treating hypertension, hyperlipidemia, premature graying of hair, and etc., has aroused wide concern for its reported potential liver toxicity. Due to its various active ingredients, the mechanisms underlying the hepatotoxicity of raw Polygonum multiflorum Thund (RPM) remain largely unknown. AIM OF THE STUDY: 1H NMR metabolomics was used to study the mechanism of RPM induced hepatotoxicity and disclosed the existence of hepatotoxicity and hepatoprotection conversion during RPM administration in mice. MATERIALS AND METHODS: Three dosages of RPM were administered by gavage to mice for consecutive 28 days. The serum and liver samples were collected and then subjected for histopathology observation, biochemical measurement and 1H NMR metabolic profiling. RESULTS: RPM caused oxidative stress and mitochondria dysfunction in mice, resulting in significant disturbance in energy metabolism, amino acid metabolism and pyrimidine metabolism and also inducing inflammatory responses. RPM induced hepatotoxicity in an apparent non-linear manner: the most severe in low dosage group, and to a less extent in medium group according to metabolomics analysis. The attenuation of liver injury in mice livers might result from the therapeutic effects, such as anti-oxidative capacity of RPM components. CONCLUSION: RPM exerted a complicated non-linear manner in healthy recipients, switching between hepatoxicity and hepatoprotection dependent on the dosage and status of the body.
Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Fígado/efeitos dos fármacos , Extratos Vegetais/farmacologia , Polygonum , Substâncias Protetoras/farmacologia , Animais , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Relação Dose-Resposta a Droga , Fígado/metabolismo , Fígado/patologia , Masculino , Medicina Tradicional Chinesa , Metabolômica , Camundongos Endogâmicos ICR , Raízes de PlantasRESUMO
Stroke is the third most common cause of death in most industrialized countries. Polygonum multiflorum (He-Shou-Wu, HSW) is one of the traditional Chinese medicines with multiple pharmacological activities which is widely used in Chinese recipe. This study aims to explore the protective effect of HSW on ischemic stroke rat model and to elucidate the underlying mechanisms. The mortality rate, neurological deficit, cerebral infarct size, histopathology, immunohistochemistry, biochemical parameters, quantitative real-time polymerase chain reaction and western blotting were used to access the treatment effects of HSW on ischemic stroke. Proton nuclear magnetic resonance (1H NMR) based metabolomics analysis disclosed that HSW could relieve stroke rats suffering from the ischemia/reperfusion injury by ameliorating the disturbed energy and amino acids metabolisms, alleviating the oxidative stress from reactive oxygen species and reducing the inflammation. HSW treatment increased levels of cellular antioxidants that scavenged reactive oxygen species during ischemia-reperfusion via the nuclear erythroid 2-related factor 2 signaling pathway, and exert anti-inflammatory effect by decreasing the levels of inflammatory factors such as cyclooxygenase-2, interleukin-1ß, interleukin-6 and tumor necrosis factor-α. The integrated metabolomics approach showed its potential in understanding mechanisms of HSW in relieving ischemic stroke. Further study to develop HSW as an effective therapeutic agent to treat ischemic stroke is warranted.
Assuntos
Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Fallopia multiflora/química , Fármacos Neuroprotetores/farmacologia , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/metabolismo , Animais , Antioxidantes/metabolismo , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/química , Masculino , Medicina Tradicional Chinesa/métodos , Metabolômica/métodos , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Espectroscopia de Prótons por Ressonância Magnética/métodos , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismoRESUMO
Colorectal cancer (CRC) is one of the most common malignant tumors worldwide, occurring in the colon or rectum portion of large intestine. With marked antioxidant, anti-inflammation and anti-tumor activities, Camellia nitidissima Chi has been used as an effective treatment of cancer. The azoxymethane/dextran sodium sulfate (AOM/DSS) induced CRC mice model was established and the prevention effect of C. nitidissima Chi extracts on the evolving of CRC was evaluated by examination of neoplastic lesions, histopathological inspection, serum biochemistry analysis, combined with nuclear magnetic resonance (NMR)-based metabolomics and correlation network analysis. C. nitidissima Chi extracts could significantly inhibit AOM/DSS induced CRC, relieve the colonic pathology of inflammation and ameliorate the serum biochemistry, and could significantly reverse the disturbed metabolic profiling toward the normal state. Moreover, the butanol fraction showed a better efficacy than the water-soluble fraction of C. nitidissima Chi. Further development of C. nitidissima Chi extracts as a potent CRC inhibitor was warranted.
RESUMO
Datura metel L. (D. metel) is one well-known folk medical herb with wide application and also the most abused plants all over the world, mainly for spiritual or religious purpose, over-dosing of which often produces poisonous effects. In this study, mice were orally administered with the extract of D. metel once a day at doses for 10 mg/kg and 40 mg/kg for consecutive 4 days, 1H NMR based metabolomics approach aided with histopathological inspection and biochemical assays were used for the first time to study the psychoactive and toxic effects of D. metel. Histopathological inspection revealed obvious hypertrophy of hepatocytes, karyolysis and karyorrhexis in livers as well as distinct nerve cell edema, chromatolysis and lower nuclear density in brains. The increased tissue level of methane dicarboxylic aldehyde (MDA) and superoxide dismutase (SOD), decreased tissue level of glutathione (GSH) along with increased serum level of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) suggested brain and liver injury induced by D. metel. Orthogonal signal correction-partial least squares-discriminant analysis (OSC-PLS-DA) of NMR profiles supplemented with correlation network analysis revealed significant altered metabolites and related pathway that contributed to oxidative stress, energy metabolism disturbances, neurotransmitter imbalance and amino acid metabolism disorders.
Assuntos
Encéfalo/efeitos dos fármacos , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Datura metel/toxicidade , Fígado/efeitos dos fármacos , Extratos Vegetais/toxicidade , Animais , Encéfalo/metabolismo , Metabolismo Energético/efeitos dos fármacos , Glutationa/metabolismo , Fígado/metabolismo , Espectroscopia de Ressonância Magnética , Metabolômica , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Superóxido Dismutase/metabolismoRESUMO
Sepsis, characterized by systemic inflammation, often leads to end-organ dysfunction, such as acute kidney injury (AKI). Despite of the severity and frequency of septic AKI in clinic, its pathogenesis is still poorly understood. Combined with histopathology evaluations, mortality assessments, biochemical evaluations, reverse transcription (RT) reaction and quantitative real-time PCR, and western blot, 1H NMR-based metabolomics approach was applied to investigate effects of Huang-Lian-Jie-Du-Decotion (HLJDD), a traditional Chinese medicine prescription, and its four component herbs on lipopolysaccharide (LPS)-induced septic AKI and the underlying mechanism. LPS induced kidney dysfunction via activation of NF-κB and mitogen-activated protein kinases (MAPKs), by excessive production of IL-6, tumor necrosis factor-α, inducible nitric oxide synthase, and COX-2, producing perturbance in energy metabolism and oxidative stress. HLJDD and its component herbs could effectively inhibit LPS-induced AKI in mice by inhibiting NF-κB and MAPK activation and activating the Akt/HO-1 pathway, and by markedly ameliorating disturbances in oxidative stress and energy metabolism induced by LPS. The four-component herbs could complement each other.
RESUMO
The presentstudy is to investigate the chemical constituents of needles of Taxus canadensis. The constituent was isolated by various chromatographic methods, and the chemical structure was elucidated on the basis of spectral analysis. A new biflavone was isolated and identified as 3"'-hydroxy-4"', 7-dimethylamentoflavone.
Assuntos
Flavonas/isolamento & purificação , Extratos Vegetais/isolamento & purificação , Folhas de Planta/química , Taxus/química , Flavonas/química , Estrutura Molecular , Extratos Vegetais/químicaRESUMO
The anticonvulsive properties of diazepam have been extensively studied, mainly focusing on the γ-amino butyrate (GABA) system. The aim of this investigation was to integrally analyze the metabolic events related to neuroprotection of diazepam on anisatin-induced convulsive seizures by a NMR-based metabolomic approach combined with histopathological examination and behavior examination. Multivariate analysis on metabolic profiles of the piriform cortex and cerebellum of mice revealed that diazepam could relieve mice suffering from the convulsive seizures by recovering destructed neurotransmitter and neuromodulator metabolism, ameliorating oxidative stress, alleviating the disturbance in energy, amino acid and nucleic acid metabolism in anisatin intoxicated mice. This integrated metabolomics study provided a powerful and highly effective approach to elucidate therapeutic effects and assessed the safety of diazepam. This study should be helpful for our understanding of convulsive seizures, and provide a holistic view of the treatment effects of benzodiazepine on convulsive seizures.
Assuntos
Encéfalo/metabolismo , Diazepam/uso terapêutico , Lactonas/toxicidade , Metabolômica/métodos , Ressonância Magnética Nuclear Biomolecular/métodos , Convulsões/metabolismo , Sesquiterpenos/toxicidade , Compostos de Espiro/toxicidade , Animais , Encéfalo/efeitos dos fármacos , Diazepam/farmacologia , Illicium , Masculino , Camundongos , Camundongos Endogâmicos ICR , Prótons , Convulsões/induzido quimicamente , Convulsões/tratamento farmacológicoRESUMO
A total of six new alkaloids, melodinhenines A-F (1-6), were isolated from Melodinus henryi. Melodinhenines A and B are new eburnan-vindolinine-type bisindole alkaloids and melodinhenines C-F are new quinolinic melodinus alkaloids. Their structures were elucidated through extensive spectroscopic methods including 2D NMR and HRESIMS analyses. The absolute configuration of 1 and 2 was determined using ECD exciton chirality method. To the best of our knowledge, this is the first report on the determination of the absolute configuration of eburnan-vindolinine-type bisindole alkaloid using this method.
Assuntos
Alcaloides/química , Apocynaceae/química , Alcaloides/isolamento & purificação , Alcaloides Indólicos/química , Alcaloides Indólicos/isolamento & purificação , Estrutura Molecular , Caules de Planta/químicaRESUMO
Taxus canadensis distributed mainly in North America, such as northern Minnesota, Newfoundland, south to Wisconsin and Pennsylvania. Its composition has been shown to be very different from other species, and in recent years, some new skeletons also have been found in Canada yew. Through analysis of the taxanes content on various Taxus plants containing taxanes, the results showed a higher content of taxol in T. canadensis. Based on the current research on T. canadensis (from the research results of the author in recent years, as well as from studies of scholars in the field), the paper outlined the research progress in recent years on the chemical constituents of taxane of T. canadensis and the spectral characteristics of various types of compounds. Besides, this paper analyzed the present research about solutions for the taxol drug source crisis.
Assuntos
Hidrocarbonetos Aromáticos com Pontes/química , Extratos Vegetais/química , Plantas Medicinais/química , Taxoides/química , Taxus/química , Animais , Hidrocarbonetos Aromáticos com Pontes/síntese química , Hidrocarbonetos Aromáticos com Pontes/farmacologia , Humanos , Estrutura Molecular , Extratos Vegetais/síntese química , Extratos Vegetais/farmacologia , Taxoides/síntese química , Taxoides/farmacologiaRESUMO
Anisatin is the main convulsant component in plants of the genus Illicium, many of which are important spices or folk medicines. The neurotoxicity of anisatin has been widely investigated, mainly focusing on its action on the γ-amino butyrate (GABA) system; however, little is known about the metabolic alterations that it causes. In this study, a NMR-based metabolomic approach was performed on the extracts of cortexes and cerebellums of mice administered with anisatin to explore the metabolic events associated with its intoxication. Orthogonal partial least squares-discriminant analysis (OPLS-DA) revealed many differential metabolites that indicated metabolic disturbance in neurotransmission and neuromodulation (GABA, glutamate, glutamine, and taurine), stress of reactive oxygen species (ROS) (ascorbate, phosphatidylcholine, choline, and ethanolamine), energy metabolism (NAD(+)i.e., nicotinamide-adenine dinucleotide, lactate, citrate, fumarate, creatine/phosphocreatine, and creatinine), amino acid metabolism (leucine, isoleucine, valine, phenylalanine, tyrosine, tryptophan, alanine, threonine, and glycine) and nucleic acid metabolism (NAD(+), nicotinamide/niacinamide, adenosine, and guanosine). This pilot metabolomic study on anisatin intoxication should help to develop a holistic view of convulsive seizures induced by anisatin, and provide a better understanding of the mechanisms.
Assuntos
Córtex Cerebelar/patologia , Lactonas/efeitos adversos , Metaboloma/efeitos dos fármacos , Metabolômica/métodos , Convulsões/induzido quimicamente , Sesquiterpenos/efeitos adversos , Compostos de Espiro/efeitos adversos , Animais , Peso Corporal/efeitos dos fármacos , Córtex Cerebelar/metabolismo , Regulação da Expressão Gênica , Illicium/química , Lactonas/administração & dosagem , Masculino , Camundongos , Camundongos Endogâmicos ICR , Ressonância Magnética Nuclear Biomolecular/métodos , Projetos Piloto , Convulsões/metabolismo , Convulsões/patologia , Sesquiterpenos/administração & dosagem , Compostos de Espiro/administração & dosagemRESUMO
AIM: To study the chemical constituents and bioactivity of the stem bark of Mitragyna diversifolia. METHOD: Compounds were isolated by various chromatographic methods. Their structures were elucidated on the basis of spectroscopic techniques (IR, UV, MS, and NMR), and they were evaluated for their cytotoxic activities by the MTT method. RESULTS: Eight triterpenes were isolated and identified as 3α, 6ß, 19α-trihydroxy-urs-12-en-28-oic acid (1), 3ß, 6ß, 19α-trihydroxy-urs-12-en-28-oic acid (2), 3-oxo-6ß-19α-dihydroxy-urs-12-en-28-oic acid (3), 3ß, 6ß, 19α-trihydroxy-urs-12-en-24, 28-dioic acid 24-methyl ester (4), 3ß, 6ß, 19α, 24-tetrahydroxy-urs-12-en-28-oic acid (5), rotundic acid (6), 23-nor-24-exomethylene- 3ß, 6ß, 19α-trihydroxy-urs-12-en-28-oic acid (7), and pololic acid (8), respectively. All of the isolates were tested against two human tumor cell lines, MCF-7 (breast) and HT-29 (colon). CONCLUSION: Compound 1 was a new triterpene. Compounds 5 - 7 exhibited potent inhibitory effects on the growth of MCF-7 and HT-29 cells, and the others showed no cytotoxicity.
Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Mitragyna/química , Neoplasias/tratamento farmacológico , Fitoterapia , Extratos Vegetais/uso terapêutico , Triterpenos/uso terapêutico , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Células HT29 , Humanos , Células MCF-7 , Estrutura Molecular , Casca de Planta/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Caules de Planta/química , Triterpenos/química , Triterpenos/isolamento & purificação , Triterpenos/farmacologiaRESUMO
Matrine and sophocarpine are two major matrine-type alkaloids included in the traditional Chinese medicine (TCM) Kushen (the root of Sophora flavescens Ait.). They have been widely used clinically in China, however with few reports concerning their potential toxicities. This study investigated the developmental toxicity and neurotoxicity of matrine and sophocarpine on zebrafish embryos/larvae from 0 to 96/120h post fertilization (hpf). Both drugs displayed teratogenic and lethal effects with the EC50 and LC50 values at 145 and 240mg/L for matrine and 87.1 and 166mg/L for sophocarpine, respectively. Exposure of matrine and sophocarpine significantly altered spontaneous movement and inhibited swimming performance at concentrations below those causing lethality and malformations, indicating a neurotoxic potential of both drugs. The results are in agreement with most mammalian studies and clinical observations.
Assuntos
Alcaloides/toxicidade , Cardiotoxinas/toxicidade , Neurotoxinas/toxicidade , Quinolizinas/toxicidade , Teratogênicos/toxicidade , Animais , Comportamento Animal/efeitos dos fármacos , Embrião não Mamífero/anormalidades , Embrião não Mamífero/efeitos dos fármacos , Desenvolvimento Embrionário/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Atividade Motora/efeitos dos fármacos , Miocárdio/patologia , Notocorda/anormalidades , Cauda/anormalidades , Peixe-Zebra/anormalidades , MatrinasRESUMO
A total of 10 new indole alkaloids, tabercarpamines A-J (1-10), were isolated from the leaves of Tabernaemontana corymbosa. Tabercarpamines C-F (3-6) are rare C-14/C-15-seco-tabersonine-type monoterpenoid indole alkaloids, and 5 and 6 are the first examples with a lactone linkage between C-14 and C-20. The structures of these alkaloids were elucidated using spectroscopic methods, and the absolute configurations of 1 and 2 were determined using the ECD exciton chirality method. In addition, an MTT assay was used to examine the growth-inhibitory effects of all new isolates and of two known isolates on MCF-7, HepG2, and SMMC-7721 cells; 1 exhibited significant inhibitory effects against these three human cancer cell lines with IC50 values of 8.54, 3.31, and 6.76 µM, respectively. Additionally, the results from the annexin-V/PI double-staining assay indicated that 1 might inhibit the proliferation of HepG2 cells by inducing apoptosis.
Assuntos
Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Medicamentos de Ervas Chinesas/isolamento & purificação , Medicamentos de Ervas Chinesas/farmacologia , Alcaloides Indólicos/isolamento & purificação , Alcaloides Indólicos/farmacologia , Tabernaemontana/química , Antineoplásicos Fitogênicos/química , Ensaios de Seleção de Medicamentos Antitumorais , Medicamentos de Ervas Chinesas/química , Células Hep G2 , Humanos , Alcaloides Indólicos/química , Estrutura Molecular , Folhas de Planta/química , Quinolinas/química , Quinolinas/isolamento & purificação , Quinolinas/farmacologiaRESUMO
Fourteen new dammarane-type triterpenoids (1-14) and 11 known analogues were isolated from the stem bark of Dysoxylum binecteriferum. The absolute configurations were established by comparison with the literature or by Mo2(OAc)4-induced electronic circular dichroism data. All isolates were evaluated for their cytotoxicities against three human cancer cell lines as well as their inhibitory effects on lipopolysaccharide-induced nitric oxide production in RAW264.7 cells. Compounds 4 and 8 displayed moderate cytotoxicities against HepG2 with IC50 values of 6.5 and 8.0 µM, respectively.