Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 817
Filtrar
1.
Zhongguo Zhong Yao Za Zhi ; 46(2): 306-311, 2021 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-33645116

RESUMO

Liver is the main place of drug metabolism. Mitochondria of hepatocytes are important targets of drug-induced liver injury. Mitochondrial autophagy could maintain the healthy operation of mitochondria in cells and the stable proliferation of cells. Therefore, the use of mitochondrial autophagy to remove damaged mitochondria is an important strategy of anti-drug-induced liver injury. Active ingredients that could enhance mitochondrial autophagy are contained in many traditional Chinese medicines, which could regulate the mitochondrial autophagy to alleviate relevant diseases. However, there are only a few reports on how to accurately and efficiently identify and evaluate such components targeting mitochondria from traditional Chinese medicine. Liquid chromatography-mass spectro-metry(LC-MS) combined with serum pharmacology in vivo can be used to accurately and efficiently find active ingredients of traditional Chinese medicine acting on mitochondrial targets. This paper reviewed the research ideas and methods of traditional Chinese medicine ingredients for increasing the hepatotoxicity of mitochondrial autophagy, in order to provide new ideas and methods for the study of active ingredients of traditional Chinese medicine targeting mitochondria.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Medicamentos de Ervas Chinesas , Medicamentos de Ervas Chinesas/toxicidade , Humanos , Medicina Tradicional Chinesa , Mitocôndrias
2.
Zhongguo Zhong Yao Za Zhi ; 46(1): 162-170, 2021 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-33645066

RESUMO

To study the time-toxicity relationship and mechanism of Gardeniae Fructus extract on the hepatoxicity in rats. Rats were randomly divided into C group(0 day), D5 group(5 days), D12 group(12 days), D19 group(19 days), and D26 group(7 days recovery after 19 days of administration). The rats in normal group received normal saline through intragastric administration, and the rats in other groups received 10 g·kg~(-1 )Gardeniae Fructus extract through intragastric administration. After the final administration, the livers were collected. Hematoxylin-eosin staining was used to observe the histopathological changes in the liver tissue. Total liver proteins were extracted for proteomic analysis, detected by the Nano-ESI liquid-mass spectrometry system and identified by Protein Disco-very software. SIEVE software was used for relative quantitative and qualitative analysis of proteins. The protein-protein interaction network was constructed based on STRING. Cytoscape software was used for cluster analysis of differential proteins. Kyoto encyclopedia of genes and genomes(KEGG) database was used to perform enrichment signal pathway analysis. Pearson correlation analysis was performed for the screened differential protein expression and liver pathology degree score. The results showed that the severity of liver injury in D5, D12 and D19 groups was significantly higher than that in group C. The degree of liver damage in D5 group was slightly higher than that in D12 and D19 groups, with no significant difference between group D26 and group C. Totally 147 key differential proteins have been screened out by proteomics and mainly formed 6 clusters, involving in drug metabolism pathways, retinol metabolism pathways, proteasomes, amino acid biosynthesis pathways, and glycolysis/gluconeogenesis pathways. The results of Pearson correlation analysis indicated that differential protein expressions had a certain temporal relationship with the change of liver pathological degree. The above results indicated that the severity of liver damage caused by Gardeniae Fructus extract did not increase with time and would recover after drug with drawal. The above pathways may be related to the mechanism of liver injury induced by Gardeniae Fructus extract.


Assuntos
Medicamentos de Ervas Chinesas , Gardenia , Animais , Medicamentos de Ervas Chinesas/toxicidade , Frutas , Fígado , Proteômica , Ratos , Transdução de Sinais
3.
J Ethnopharmacol ; 264: 113247, 2021 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-32800929

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Tetrastigma hemsleyanum Diels et Gilg (T.hemsleyanum), a rare herbal plant distributed in subtropical areas of mainland China, has become a focus of scientific attention in recent years because of its high traditional value, including uses for treatment of children with fever, pneumonia, asthma, rheumatism, hepatitis, menstrual disorders, scrofula, and pharynx pain. AIM: This systematic review aims to provide an insightful understanding of traditional uses, chemical composition, pharmacological effect and clinical application of T. hemsleyanum, and lay a foundation for the further study and for the utilization of T. hemsleyanum resource. MATERIALS AND METHODS: A domestic and overseas literature search in known databases was conducted for published articles using the relevant keywords. RESULTS: One hundred and forty-two chemical constituents identified from T. hemsleyanum have been reported, including flavonoids, phenolic acids, polysaccharide, organic acids, fatty acids, terpenoids, steroids, amino acid and others. Among these components, flavonoids and polysaccharides were the representative active ingredients of T. hemsleyanum, which have been widely investigated. Modern pharmacological studies have shown that these components exhibited various pharmacological activities, such as anti-inflammatory, antioxidant, antivirus, antitumor, antipyretic, anti-hepatic injury, immunomodulatory, antibacterial etc. Moreover, different toxicological studies indicated that the clinical dosage of T. hemsleyanum was safe and reliable. CONCLUSIONS: Modern pharmacological studies have well supported and clarified some traditional uses, and T. hemsleyanum has a good prospect for the development of new drugs due to these outstanding properties. However, the present findings did not provide an in-depth evaluation of bioactivity of the extracts, the composition of its active extracts was not clear. Moreover, they were insufficient to satisfactorily explain some mechanisms of action. Data regarding many aspects of T. hemsleyanum, such as links between the traditional uses and bioactivities, pharmacokinetics, quality control standard and the clinical value of active compositions is still limited which need more attention.


Assuntos
Medicamentos de Ervas Chinesas/toxicidade , Etnofarmacologia/métodos , Medicina Tradicional Chinesa/métodos , Compostos Fitoquímicos/toxicidade , Plantas Medicinais , Animais , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/uso terapêutico , Antineoplásicos Fitogênicos/toxicidade , Medicamentos de Ervas Chinesas/isolamento & purificação , Medicamentos de Ervas Chinesas/uso terapêutico , Etnofarmacologia/tendências , Humanos , Medicina Tradicional Chinesa/tendências , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/uso terapêutico
4.
J Ethnopharmacol ; 264: 113292, 2021 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-32841697

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The dried and nearly ripe fruits of Tetradium ruticarpum (A. Juss.) T.G. Hartley (TR) have long been used in treating headache and gastrointestinal disorders in oriental medicine. TR is usually processed by stir-frying with licorice extract before use. Although processing procedure is considered as the way to relieve pungent smell, reduce toxicity, and improve efficacy, its effects on TR's toxicity and efficacy and bioactive compound profiles are largely unknown. AIM OF THE STUDY: The purposes of the study are to evaluate the acute toxicity, efficacy and variation of toxic and effective components of TR before and after processing, and to explore the possible mechanism of how the processing procedure affect the quality of TR as a herbal medicine. MATERIALS AND METHODS: Volatile oil, aqueous extract and ethanol extract of raw and processed TR were tested for their acute toxicity, analgesic, and anti-inflammatory effects in mouse models, respectively. To identify potential toxic and effective components, the extracts were analyzed with gas chromatography-mass spectrometry and ultra-performance liquid chromatography - quadrupole time-of-flight mass spectrometry, followed by fold-change-filtering analysis. RESULTS: LD50 and LD5 tests indicated that although the aqueous extract has higher toxicity than volatile oil and ethanol extract, the use of TR is safe under the recommended does. The processing procedure could effectively decrease the toxicity of all three extracts with the largest decrease in volatile oil, which is likely due to the loss of volatile compounds during processing. Analgesic and anti-inflammatory studies suggested that volatile oil and ethanol extract of TR have better efficacy than the aqueous extract and the processing procedure significantly enhanced the efficacy of these two former extracts, whereas processing showed no substantially effects on the bioactivities of aqueous extract. Integrated analysis of animal trial and chromatographic analyses indicated that indole and quinolone type alkaloids, limonoids, amides and 18ß-glycyrrhetinic acid were identified as the potential main contributors of TR's efficacy, whereas hydroxy or acetoxy limonoid derivates and coumarins could be the major causes of toxicity. Moreover, the reduced toxicity and improved efficacy of the processed TR are liked due to the licorice ingredients and altered alkaloids with better solubility. CONCLUSIONS: In summary, the integrated toxicity and efficacy analyses of volatile, aqueous and ethanol extracts of TR indicated that the processing procedure could effectively reduce its acute toxicity in all three extracts and enhance its analgesic and anti-inflammatory effects in volatile and ethanol extracts. The promising candidate compounds related to the toxicity and efficacy of TR were also identified. The results could expand our understanding of the value of the standard processing procedure of TR, be valuable to the quality control of TR manufacturing and administration, as well as support clinical rational and safety applications of this medicinal plant.


Assuntos
Analgésicos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Evodia , Testes de Toxicidade Aguda/métodos , Analgésicos/isolamento & purificação , Analgésicos/toxicidade , Animais , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/toxicidade , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas/isolamento & purificação , Medicamentos de Ervas Chinesas/toxicidade , Edema/tratamento farmacológico , Edema/metabolismo , Feminino , Masculino , Camundongos , Camundongos Endogâmicos ICR , Medição da Dor/efeitos dos fármacos , Medição da Dor/métodos , Distribuição Aleatória , Resultado do Tratamento
5.
J Ethnopharmacol ; 265: 113441, 2021 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-33027642

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Kyung-Ok-Ko (KOK), a traditional medicinal formula composed of Rehmannia glutinosa (Gaertn.) DC, Poria cocos (Schw.) Wolf, Korean Red Panax ginseng C.A.Mey, and honey, has been used to treat amnesia and dementia. KOK has also been shown to ameliorate transient cerebral global ischemia-induced brain damage, but the antidepressant-like effect of KOK has not been examined. AIM OF THE STUDY: This study examined the antidepressant-like effect of KOK in an immobilization-induced stress mouse and its mechanisms of action. MATERIALS AND METHODS: The animals in the stress group were immobilized for two hours a day for two weeks. KOK at a dose of 1 g/kg/day was administered orally to the stressed mice for two weeks in advance of their immobilization. A forced swimming test was performed to analyze their depressive behaviors. To examine the anti-inflammatory or antioxidative effects of KOK, the murine macrophage cell line, RAW 264.7 cells and human neuroblastoma cell, SH-SY5Y cells, were treated with lipopolysaccharide (LPS) and hydrogen peroxide, respectively. RESULT: The KOK extract showed no significant toxicity when the cells were treated with a KOK extract at 5, 10, 25, 50, and 100 µg/mL. The KOK ethanol extract reduced LPS-induced TNF-α production, inducible nitric oxide (iNOS) mRNA level, and the levels of MAPK and p38 phosphorylation in RAW 264.7 cells. KOK also suppressed H2O2-induced cell death and the production of reactive oxygen species (ROS) in SH-SY5Y cells. In the forced swimming test, KOK induced a decrease in immobility and an increase in climbing activity. Finally, the administration of KOK reversed the up-regulation of IkB-α phosphorylation in the stressed mouse cortex. CONCLUSION: KOK might be useful for the treatment of depression caused by environmental and lifestyle-related stress.


Assuntos
Depressão/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Inflamação/tratamento farmacológico , Estresse Psicológico/tratamento farmacológico , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/toxicidade , Antidepressivos/administração & dosagem , Antidepressivos/farmacologia , Antidepressivos/toxicidade , Comportamento Animal/efeitos dos fármacos , Linhagem Celular Tumoral , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/toxicidade , Humanos , Inflamação/patologia , Lipopolissacarídeos , Macrófagos/efeitos dos fármacos , Macrófagos/patologia , Masculino , Camundongos , Camundongos Endogâmicos ICR , Óxido Nítrico/metabolismo , Células RAW 264.7 , Espécies Reativas de Oxigênio/metabolismo
6.
Zhongguo Zhong Yao Za Zhi ; 45(22): 5567-5575, 2020 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-33350220

RESUMO

As a most important Chinese materia medica, Aconiti Lateralis Radix Praeparata(Fuzi) had been widely used in China for thousands of years. This herbalogical study was systematically performed based on variation characteristics of the naming, habitat, harvesting, processing and properties. The sharp toxicity of Fuzi had been well known since the spring and autumn period in the history, which was much earlier than that its medical properties was understood and applied. Sichuan province was regarded as the geo-authentic region of Fuzi all along, where the best quality goods could be provided for clinic use. The study showed the harvesting time of Fuzi was changing in different periods, and the possible effects were of climate change and artificial planting. The perishable characteris-tics of Fuzi severely limited its storage period; therefore, different kinds of storage methods were effectively used since Tang Dynasty. For thousands of years, Fuzi had been processed with various accessories to reduce toxicity, while simultaneously the study on processing mechanism was on going all the time. Fuzi was widely used in clinical practice to cure Yang depletion syndrome, which was based on its function of enhancing Yang and removing cold. Along with the further study on quality evaluation standard, Fuzi will probably get a much wider range of applications.


Assuntos
Aconitum , Medicamentos de Ervas Chinesas , China , Medicamentos de Ervas Chinesas/toxicidade , Extratos Vegetais
7.
Ecotoxicol Environ Saf ; 205: 111342, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32971455

RESUMO

Radix aconiti lateralis (Fuzi) is widely used in China as a traditional Chinese medicine for the treatment of asthenia, pain and inflammation. However, its toxic alkaloids often lead to adverse reactions. Currently, most of the toxicity studies on Fuzi are focused on the heart and nervous system, and more comprehensive toxicity studies are needed. In this study, based on the previous reports of Fuzi hepatotoxicity, serum pharmacochemistry and network toxicology were used to screen the potential toxic components of Heishunpian(HSP), a processed product of Fuzi, and to explore the possible mechanism of HSP-induced hepatotoxicity. The results obtained are expressed based on the toxicological evidence chain (TEC). It was found that 22 potential toxic components screened can affect Th17 cell differentiation, Jak-STAT signaling pathway, glutathione metabolism, and other related pathways by regulating AKT1, IL2, F2, GSR, EGFR and other related targets, which induces oxidative stress, metabolic disorders, cell apoptosis, immune response, and excessive release of inflammatory factors, eventually inducing liver damage in rats. This is the first study on HSP-induced hepatotoxicity based on the TEC concept, providing references for further studies on the toxicity mechanism of Fuzi.


Assuntos
Aconitum/química , Alcaloides/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/patologia , Medicamentos de Ervas Chinesas/toxicidade , Modelos Biológicos , Alcaloides/sangue , Alcaloides/isolamento & purificação , Animais , Apoptose/efeitos dos fármacos , Doença Hepática Induzida por Substâncias e Drogas/sangue , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , China , Medicamentos de Ervas Chinesas/isolamento & purificação , Medicamentos de Ervas Chinesas/farmacocinética , Masculino , Medicina Tradicional Chinesa , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar
8.
Turk Kardiyol Dern Ars ; 48(4): 410-424, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32519978

RESUMO

OBJECTIVE: The aim of this study was to evaluate the effectiveness of plants used in the formulations of traditional Chinese medicine (TCM), which were also used in clinical trials to treat patients with the novel coronavirus COVID-19, and to assess their effects on the cardiovascular system. METHODS: A literature review of PubMed, ResearchGate, ScienceDirect, the Cochrane Library, and TCM monographs was conducted and the effects of the plants on the cardiovascular system and the mechanisms of action in COVID-19 treatment were evaluated. RESULTS: The mechanism of action, cardiovascular effects, and possible toxicity of 10 plants frequently found in TCM formulations that were used in the clinical treatment of COVID-19 were examined. CONCLUSION: TCM formulations that had been originally developed for earlier viral diseases have been used in COVID-19 treatment. Despite the effectiveness seen in laboratory and animal studies with the most commonly used plants in these formulations, the clinical studies are currently insufficient according to standard operating procedures. More clinical studies are needed to understand the safe clinical use of traditional plants.


Assuntos
Sistema Cardiovascular/efeitos dos fármacos , Infecções por Coronavirus/terapia , Medicamentos de Ervas Chinesas/uso terapêutico , Medicina Tradicional Chinesa , Pneumonia Viral/terapia , Animais , Antiarrítmicos/farmacologia , Antiarrítmicos/uso terapêutico , Antiarrítmicos/toxicidade , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/toxicidade , Anticolesterolemiantes/farmacologia , Anticolesterolemiantes/uso terapêutico , Anticolesterolemiantes/toxicidade , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/uso terapêutico , Anti-Hipertensivos/toxicidade , Antivirais/farmacologia , Antivirais/uso terapêutico , Antivirais/toxicidade , Bloqueadores dos Canais de Cálcio/farmacologia , Bloqueadores dos Canais de Cálcio/uso terapêutico , Bloqueadores dos Canais de Cálcio/toxicidade , Interações Medicamentosas , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/toxicidade , Humanos , Pandemias , Inibidores da Agregação de Plaquetas/farmacologia , Inibidores da Agregação de Plaquetas/uso terapêutico , Inibidores da Agregação de Plaquetas/toxicidade , Vasodilatadores/farmacologia , Vasodilatadores/uso terapêutico , Vasodilatadores/toxicidade
9.
Toxicol Appl Pharmacol ; 401: 115110, 2020 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-32533954

RESUMO

Melanoma is characterized by high malignancy and early onset of metastasis. Epithelial-to-mesenchymal transition (EMT) is an early event during tumor metastasis. Tumor cells that develop EMT can escape apoptosis, but they are vulnerable to ferroptosis inducers. Gambogenic acid (GNA), a xanthone found in Gamboge, has cytotoxic effects in highly invasive melanoma cells. This study investigated the anti-melanoma effect and mechanism of action of GNA in TGF-ß1-induced EMT melanoma cells. We found that GNA significantly inhibited the invasion, migration and EMT in melanoma cells, and these cells exhibited small mitochondrial wrinkling (an important feature of ferroptosis). An iron chelator, but not an apoptosis inhibitor or a necrosis inhibitor, abolished the inhibitory effects of GNA on proliferation, invasion and migration of TGF-ß1-stimulated melanoma cells. GNA upregulated the expression of p53, solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) in the model cells, contributing to the mechanisms underlying GNA-induced ferroptosis. Collectively, our findings suggest that GNA induces ferroptosis in TGF-ß1-stimulated melanoma cells via the p53/SLC7A11/GPX4 signaling pathway.


Assuntos
Medicamentos de Ervas Chinesas/toxicidade , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Ferroptose/efeitos dos fármacos , Melanoma/metabolismo , Neoplasias Cutâneas/metabolismo , Xantenos/toxicidade , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Medicamentos de Ervas Chinesas/uso terapêutico , Transição Epitelial-Mesenquimal/fisiologia , Ferroptose/fisiologia , Humanos , Melanoma/tratamento farmacológico , Melanoma/patologia , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologia , Xantenos/uso terapêutico
10.
Adv Exp Med Biol ; 1241: 139-166, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32383120

RESUMO

Environmental and iatrogenic exposures contribute significantly to human diseases, including cancer. The list of known human carcinogens has recently been extended by the addition of aristolochic acids (AAs). AAs occur primarily in Aristolochia herbs, which are used extensively in folk medicines, including Traditional Chinese Medicine. Ingestion of AAs results in chronic renal disease and cancer. Despite importation bans imposed by certain countries, herbal remedies containing AAs are readily available for purchase through the internet. With recent advancements in mass spectrometry, next generation sequencing, and the development of integrated organs-on-chips, our knowledge of cancers associated with AA exposure, and of the mechanisms involved in AA toxicities, has significantly improved. DNA adduction plays a central role in AA-induced cancers; however, significant gaps remain in our knowledge as to how cellular enzymes promote activation of AAs and how the reactive species selectively bind to DNA and kidney proteins. In this review, I describe pathways for AAs biotransformation, adduction, and mutagenesis, emphasizing novel methods and ideas contributing to our present understanding of AA toxicities in humans.


Assuntos
Ácidos Aristolóquicos/efeitos adversos , Ácidos Aristolóquicos/metabolismo , Medicamentos de Ervas Chinesas/efeitos adversos , Medicamentos de Ervas Chinesas/metabolismo , Aristolochia/efeitos adversos , Aristolochia/química , Ácidos Aristolóquicos/toxicidade , Biotransformação , Medicamentos de Ervas Chinesas/toxicidade , Humanos , Medicina Tradicional Chinesa/efeitos adversos
11.
Chin J Nat Med ; 18(3): 196-205, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32245589

RESUMO

With the internationally growing popularity of traditional Chinese medicine (TCM), TCM-induced nephropathy has attracted public attention. Minimizing this toxicity is an important issue for future research. Typical nephrotoxic TCM drugs such as Aristolochic acid, Tripterygium wilfordii Hook. f, Rheum officinale Baill, and cinnabar mainly damage renal proximal tubules or cause interstitial nephritis. Transporters in renal proximal tubule are believed to be critical in the disposition of xenobiotics. In this review, we provide information on the alteration of renal transporters by nephrotoxic TCMs, which may be helpful for understanding the nephrotoxic mechanism of TCMs and reducing adverse effects. Studies have proven that when administering nephrotoxic TCMs, the expression or function of renal transporters is altered, especially organic anion transporter 1 and 3. The alteration of these transporters may enhance the accumulation of toxic drugs or the dysfunction of endogenous toxins and subsequently sensitize the kidney to injury. Transporters-related drug combination and clinical biomarkers supervision to avoid the risk of future toxicity are proposed.


Assuntos
Medicamentos de Ervas Chinesas/toxicidade , Nefropatias/induzido quimicamente , Medicina Tradicional Chinesa/efeitos adversos , Proteína 1 Transportadora de Ânions Orgânicos/metabolismo , Transportadores de Ânions Orgânicos Sódio-Independentes/metabolismo , Animais , Humanos , Rim/efeitos dos fármacos
12.
Zhongguo Zhong Yao Za Zhi ; 45(2): 412-417, 2020 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-32237326

RESUMO

The bilirubin metabolism mediated by the phase Ⅱ metabolizing enzyme UGT1A1 in the liver was evaluated to study the potential hepatotoxicity risk based on investigation on the inhibitory effect of rhein and its metabolites on the UGT1A1 enzyme in Rhei Radix et Rhizoma. Firstly, in vitro liver microsomes incubation was used to initiate the phase Ⅱ metabolic reaction to investigate the inhibitory effect of rheinon UGT1A1 enzyme. Secondly, the phase Ⅰ and phase Ⅱ metabolic reactions were initiated to investigate the hepatotoxicity risk of rhein metabolites. It was found that the rhein and its phase Ⅱ metabolites had no significant inhibitory effect on UGT1A1 enzyme, but its phase Ⅰ metabolites significantly reduced UGT1A1 enzyme activity. Based on the metabolites analysis, it is speculated that the rhein phase Ⅰ metabolite rheinhydroxylate and its tautomers have certain hepatotoxicity risks, while the toxicity risk induced by the prototype and phase Ⅱ metabolites of rheinglucoside, rheinglucuronic acid and rhein sulfate is small.


Assuntos
Antraquinonas/toxicidade , Doença Hepática Induzida por Substâncias e Drogas , Medicamentos de Ervas Chinesas/toxicidade , Fígado/efeitos dos fármacos , Microssomos Hepáticos/efeitos dos fármacos , Glucuronosiltransferase/metabolismo , Humanos , Fígado/enzimologia , Rizoma
13.
Zhongguo Zhong Yao Za Zhi ; 45(4): 755-763, 2020 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-32237475

RESUMO

The aim of this paper was to observe the toxic effect of Tripterygium Glycosides Tablets on the reproductive system of Ⅱ type collagen induced arthritis(CIA) male rats, and to explore the toxic mechanism preliminarily. Fifty SD rats were randomly divided into normal control group(Con), model group(CIA), Tripterygium Glycosides Tablets clinical equivalent dose groups of 1, 2, 4 times(9, 18, 36 mg·kg~(-1)), 10 rats in each group, and were given by gavage once a day for 42 days after the first immunization. The organ index of testis and epididymis were calculated on days 21 and 42. Histopathological and morphological changes of testis and epididymis were observed under optical microscope. Sperm count, sperm malformation rate and sperm kinetic parameters in epididymal tissues were observed by computer assisted sperm analysis(CASA). The concentration of testosterone(T), nitric oxide synthase(NOS) and aromatase(CYP19 A1) in serum were detected by ELISA. Immunohistochemistry was used to observe the expression of Bax and Bcl-2 related proteins in the apoptosis pathway of testis and epididymis. The results showed that, compared with Con group, CIA group significantly increased the rate of testicular spermatogenic tubule lesion and sperm malformation, decreased the average path speed, and no significant changes were observed in other groups. Tripterygium Glycosides Tablets at 4 times clinical equivalent dose can significantly reduce the testis index(P<0.01), each dose group can reduce the epididymis index(P<0.05). Each dose group of Tripterygium Glycosides Tablets could cause different degrees of damage to the testis and epididymis, the proportion of testicular histopathology lesions increased, the number of spermatogenic cells in the seminiferous tubules decreased, and so on. It could reduce the number of sperm, increase the rate of sperm deformity, make the parameters of sperm dynamics abnormal, and so on. Tripterygium Glycosides Tablets at 4 times dose could significantly reduce the content of serum sex hormone T and key enzyme of androgen synthesis(P<0.05 or P<0.01), but had no effect on CYP19 A1. The expression of Bax and Bcl-2 in testis and epididymis were increased by 2 and 4 times doses of Tripterygium Glycosides Tablets(P<0.05, P<0.01 or P<0.01). The results showed that 21 d administration of Tripterygium Glycosides Tablets at equal or higher doses could induce obvious toxic effect to the reproductive organs of CIA male rats, and lower the level of serum sex hormone T and the key enzyme of androgen synthesis, NOS. The mechanism of abnormal changes of Bax and Bcl-2 in Testis and epididymis is still to be elucidated.


Assuntos
Medicamentos de Ervas Chinesas/toxicidade , Genitália Masculina/efeitos dos fármacos , Glicosídeos/toxicidade , Espermatozoides/efeitos dos fármacos , Testículo/efeitos dos fármacos , Tripterygium/química , Animais , Artrite Experimental , Masculino , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Espermatozoides/patologia , Comprimidos , Testículo/patologia
14.
BMC Complement Med Ther ; 20(1): 73, 2020 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-32143619

RESUMO

BACKGROUND: Recent studies indicated that seeded fibril formation and toxicity of α-synuclein (α-syn) play a main role in the pathogenesis of certain diseases including Parkinson's disease (PD), multiple system atrophy, and dementia with Lewy bodies. Therefore, examination of compounds that abolish the process of seeding is considered a key step towards therapy of several synucleinopathies. METHODS: Using biophysical, biochemical and cell-culture-based assays, assessment of eleven compounds, extracted from Chinese medicinal herbs, was performed in this study for their effect on α-syn fibril formation and toxicity caused by the seeding process. RESULTS: Salvianolic acid B and dihydromyricetin were the two compounds that strongly inhibited the fibril growth and neurotoxicity of α-syn. In an in-vitro cell model, these compounds decreased the insoluble phosphorylated α-syn and aggregation. Also, in primary neuronal cells, these compounds showed a reduction in α-syn aggregates. Both compounds inhibited the seeded fibril growth with dihydromyricetin having the ability to disaggregate preformed α-syn fibrils. In order to investigate the inhibitory mechanisms of these two compounds towards fibril formation, we demonstrated that salvianolic acid B binds predominantly to monomers, while dihydromyricetin binds to oligomeric species and to a lower extent to monomers. Remarkably, these two compounds stabilized the soluble non-toxic oligomers lacking ß-sheet content after subjecting them to proteinase K digestion. CONCLUSIONS: Eleven compounds were tested but only two showed inhibition of α-syn aggregation, seeded fibril formation and toxicity in vitro. These findings highlight an essential beginning for development of new molecules in the field of synucleinopathies treatment.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/toxicidade , Extratos Vegetais/farmacologia , Extratos Vegetais/toxicidade , alfa-Sinucleína/antagonistas & inibidores , Animais , Benzofuranos/farmacologia , Benzofuranos/toxicidade , Flavonóis/farmacologia , Flavonóis/toxicidade , Células HEK293 , Humanos , Camundongos , Estrutura Molecular , Agregação Patológica de Proteínas , Sinucleinopatias/tratamento farmacológico
15.
Adv Pharmacol ; 87: 301-346, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32089237

RESUMO

Traditional Chinese medicine (TCM) has been used to treat numerous kinds of diseases for more than 2000 years in eastern Asian countries. A portion of the TCM herbal and mineral products are believed to be toxic according to modern standards, and are still widely prescribed in the clinic. However, some TCM products considered to be non-toxic or low-toxic have been reported to possess significant toxicological effects on different organs in both animal and human models. In this review, we define the term "toxic" in TCM, and then we summarize the advances in pharmacology and toxicology research of Toxic Traditional Chinese Medicine (TTCM), including Chinese aconite (Fu Zi), Arsenic Trioxide, Tripterygium wilfordii Hook f. (Thunder God Vine), herbal drugs derived from plants in the Aristolochiaceae Juss. family (Ma Dou Ling), and other TCM products. Finally, the compatibility art of TCM and modern pharmaceutical approaches to manage undesired toxicity of TTCM is discussed. Promoting pharmacology and toxicology studies of TTCM and non-toxic TCM is critical for the further development and safety of TCM in clinical practice.


Assuntos
Medicamentos de Ervas Chinesas/toxicidade , Medicina Tradicional Chinesa , Minerais/toxicidade , Animais , Humanos , Tripterygium/química
16.
Chin J Nat Med ; 18(1): 57-69, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31955824

RESUMO

Diterpenoid lactones (DLs), a group of furan-containing compounds found in Dioscorea bulbifera L. (DB), have been reported to be associated with hepatotoxicity. Different hepatotoxicities of these DLs have been observed in vitro, but reasonable explanations for the differential hepatotoxicity have not been provided. Herein, the present study aimed to confirm the potential factors that contribute to varied hepatotoxicity of four representative DLs (diosbulbins A, B, C, F). In vitro toxic effects were evaluated in various cell models and the interactions between DLs and CYP3A4 at the atomic level were simulated by molecular docking. Results showed that DLs exhibited varied cytotoxicities, and that CYP3A4 played a modulatory role in this process. Moreover, structural variation may cause different affinities between DLs and CYP3A4, which was positively correlated with the observation of cytotoxicity. In addition, analysis of the glutathione (GSH) conjugates indicated that reactive intermediates were formed by metabolic oxidation that occurred on the furan moiety of DLs, whereas, GSH consumption analysis reflected the consistency between the reactive metabolites and the hepatotoxicity. Collectively, our findings illustrated that the metabolic regulation played a crucial role in generating the varied hepatotoxicity of DLs.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Citocromo P-450 CYP3A/metabolismo , Dioscorea/toxicidade , Medicamentos de Ervas Chinesas/toxicidade , Furanos/toxicidade , Cromatografia Líquida , Dioscorea/química , Medicamentos de Ervas Chinesas/química , Furanos/química , Células Hep G2 , Humanos , Espectrometria de Massas , Simulação de Acoplamento Molecular , Estrutura Molecular
17.
Toxicol Lett ; 323: 41-47, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-31982501

RESUMO

Gynura japonica (also named Tusanqi in Chinese) is used as a folk herbal medicine for treating blood stasis or traumatic injury. However, hundreds of hepatic sinusoidal obstruction syndrome (HSOS) cases have been reported after consumption of preparations made from G. japonica because it contains large amounts of hepatotoxic pyrrolizidine alkaloids (PAs). To date, blood pyrrole-protein adducts (PPAs) are suggested as biomarkers for the diagnosis of PA-induced HSOS in clinics. However, the concentration of PPAs in the blood is greatly affected by several factors including the amount of PA exposure, herb intake period, and blood sampling time after the last exposure. In present study, the kinetic characters of PPAs in serum and liver as well as other potential target organs were studied systematically and comprehensively following multiple exposures of PAs in G. japonica extract (GJE). As results, PPAs content reached to a plateau both in serum and liver after the mice were treated with GJE for 2 weeks on daily basis. PPAs cleared significantly slower in liver (T1/2ke∼184.6 h, ∼7.7 days) than in serum (T1/2ke∼95.8 h, ∼4.0 days). Although more than 90 % PPAs were removed 2 weeks after the last dosing, PPAs still persisted in the liver until the end of the experiment, i.e. 8 weeks after the last dosing. The results would be of great help for understanding the importance of PPAs for PA-induced toxicity and its detoxification.


Assuntos
Proteínas Sanguíneas/metabolismo , Medicamentos de Ervas Chinesas/farmacocinética , Hepatopatia Veno-Oclusiva/induzido quimicamente , Pirróis/metabolismo , Alcaloides de Pirrolizidina/farmacocinética , Animais , Medicamentos de Ervas Chinesas/toxicidade , Cinética , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Extratos Vegetais/análise , Extratos Vegetais/toxicidade , Alcaloides de Pirrolizidina/toxicidade
18.
J Ethnopharmacol ; 252: 112551, 2020 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-31923540

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Bojungikki-tang is a traditional herbal medicine used to boost immunity and reduce fatigue. However, there is not enough scientific evidence about its toxicological safety profile to support its continued clinical application. AIM OF THE STUDY: The objective of this study was to investigate the subchronic toxicity profile of Bojungikki-tang water extract (BITW) in Sprague Dawley rats who were exposed to it in multiple doses and various concentrations. MATERIALS AND METHODS: BITW was administered to rats orally, once daily at doses of 0, 500, 1000, or 2000 mg/kg/day for 13 weeks. We checked toxicological parameters including general observations, organ/body weights, food consumption, ophthalmological signs, hematological and serum biochemical values, urinalysis values and histopathological findings. RESULTS: The 13 week repeated oral administration of BITW to rats at doses at doses levels of less than or equal to 2000 mg/kg/day caused no significant toxicological changes and only minor nonsignificant changes. CONCLUSIONS: Our findings indicate that administration of BITW for up to 13 weeks may be safe and nontoxic, with a no-observed-adverse-effect-level of >2000 mg/kg/day for both male and female rats.


Assuntos
Medicamentos de Ervas Chinesas/toxicidade , Animais , Feminino , Masculino , Ratos Sprague-Dawley , Solventes/química , Testes de Toxicidade Subcrônica , Água/química
19.
Biomed Pharmacother ; 123: 109709, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31855734

RESUMO

Herb-induced liver injury (HILI) is a growing clinical and economic problem worldwide. However, the underlying mechanism of HILI remains largely unknown, which hinders the prevention and treatment of this disease. Recently evidence supports that microRNAs (miRNAs) in circulating exosomes and cells play an important role in the pathology of liver diseases. Thus, using Fructus Meliae Toosendan (FMT) as an example of hepatoxic herbal medicine, the aim of this study was to reveal the mechanisms of FMT-induced liver injury (FILI) through integrated analysis of serum exosomal miRNAs and liver miRNAs profiles on FMT ethyl acetate extract (FMT for short)-exposed mice. Two dosages of FMT (20 and 40 g/kg) were involved in this study, while only high-dose exposure induced obvious liver injury in mice. Pathway analysis of 209 differentially expressed miRNAs (DEMs) in serum exosomes between high-dose FMT and control groups exhibited that FILI might be regulated by apoptosis-related pathways, such as p53 signaling, PI3K/Akt signaling, and PTEN signaling. Integrated analysis of the mRNA targets of serum exosomal DEMs and liver DEMs of high-dose FMT group showed that autophagy was significantly enriched as one of the top canonical pathways in FILI. Hepatocyte apoptosis was then proved by TUNEL assay in the liver tissue of high-dose FMT-treated mice. Moreover, in vivo validation studies suggested that the protein expression levels of PTEN, p-AKT, p53, and BAX were indeed regulated in the mouse liver after high-dose FMT administration, indicating hepatocyte apoptosis may be mediated by these three pathways mentioned above. Intriguingly, PINK1/Parkin-mediated mitophagy was activated in high-dose FMT-treated mouse liver and the protective effect of autophagy in FILI was validated in vitro with an autophagic flux inhibitor. In addition, serum exosomal miR-222, the most downregulated miRNAs between low- and high-dose FMT treatments, might be an important event in the hepatocyte apoptosis by regulating PTEN and PPP2R2A. In conclusion, integrated analysis of microRNA profiles in mouse serum exosomes and liver cells provides insights into the hepatotoxicity mechanisms of FMT and discloses the protective role of autophagy in FILI, suggesting this method could contribute to deeply understand the mechanism of HILI and activation of autophagy may be a potentially therapeutic strategy for FILI even HILI.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Medicamentos de Ervas Chinesas/toxicidade , Exossomos/metabolismo , Fígado/metabolismo , MicroRNAs/metabolismo , Transcriptoma , Animais , Autofagia/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Hepatócitos/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , MicroRNAs/genética
20.
J Ethnopharmacol ; 250: 112489, 2020 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-31866510

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Baizi Yangxin Pills (BZYXP), a popular cinnabar (α-HgS) contained Traditional Chinese Medicines (TCMs) is widely used in clinical trials. However, mercury is one of the most toxic elements. The adverse effects of cinnabar-containing TCMs have been occasionally reported in recent years, leading to the growing concerns about their toxicity and safety. AIM OF THE STUDY: The health risks of BZYXP and cinnabar related to the mercury exposures were evaluated through blood pharmacokinetic and tissue distribution studies in rats. MATERIALS AND METHODS: The distribution of absorbed mercury in rats' blood and tissues were measured by the developed cold-vapor atomic fluorescence spectrometric method. And the tissue damages were determined through the histopathological examinations. For single dose study, the low and high oral doses were equivalent to 1 and 10-fold therapeutic dose, respectively. The multiple doses study was conducted at low and high dose levels every 12 h for 30 consecutive days. RESULTS: Significant differences of mercury blood pharmacokinetic and tissue distribution characteristics were observed between the corresponding BZYXP and cinnabar groups. The herbal ingredients in BZYXP promoted the absorption of bio-accessible mercury of cinnabar and prolonged the elimination process, posing potential health risks. Although mercury was found easily accumulated in kidney, liver and brain tissues, kidney and liver didn't show obvious damages even after 30 days consecutive administration of BZYXP or cinnabar at 10-fold clinically equivalent doses. But brain did show some histopathological changes, and autonomic activities of rats decreased, pointing the potential neurotoxicity. CONCLUSIONS: Mercury tend to be accumulated especially when over-dose or prolonged medication with cinnabar-containing TCMs are given. The mercury exposures even at therapeutic doses of BZYXP or cinnabar do pose health risks from the neurotoxicity point of view.


Assuntos
Medicamentos de Ervas Chinesas/administração & dosagem , Medicina Tradicional Chinesa/efeitos adversos , Compostos de Mercúrio/administração & dosagem , Síndromes Neurotóxicas/etiologia , Animais , Encéfalo/metabolismo , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas/farmacocinética , Medicamentos de Ervas Chinesas/toxicidade , Feminino , Rim/metabolismo , Fígado/metabolismo , Masculino , Compostos de Mercúrio/farmacocinética , Compostos de Mercúrio/toxicidade , Ratos , Ratos Sprague-Dawley , Medição de Risco , Distribuição Tecidual
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...