Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 211
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
J Cell Mol Med ; 2020 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-32073745

RESUMO

Higenamine (HG) is a natural benzylisoquinoline alkaloid isolated from Aconitum with positive inotropic and chronotropic effects. This study aimed to investigate the possible cardioprotective effects of HG combined with [6]-gingerol (HG/[6]-GR) against DOX-induced chronic heart failure (CHF) by comprehensive approaches. DOX-induced cardiotoxicity model in rats and H9c2 cells was established. Therapeutic effects of HG/[6]-GR on haemodynamics, serum indices and histopathology of cardiac tissue were analysed. Cell mitochondrial energy phenotype and cell mitochondrial fuel flex were measured by a Seahorse XFp analyser. Moreover, UHPLC-Q-TOF/MS was performed to explore the potential metabolites affecting the therapeutic effects and pathological process of CHF. To further investigate the potential mechanism of HG/[6]-GR, mRNA and protein expression levels of RAAS and LKB1/AMPK/Sirt1-related pathways were detected. The present data demonstrated that the therapeutic effects of HG/[6]-GR combination on CHF were presented in ameliorating heart function, down-regulation serum indices and alleviating histological damage of heart tissue. Besides, HG/[6]-GR has an effect on increasing cell viability of H9c2 cells, ameliorating DOX-induced mitochondrial dysfunction and elevating mitochondrial OCR and ECAR value. Metabolomics analyses showed that the therapeutic effect of HG/[6]-GR combination is mainly associated with the regulation of fatty acid metabolites and energy metabolism pathways. Furthermore, HG/[6]-GR has an effect on down-regulating RAAS pathway-related molecules and up-regulating LKB1/AMPKα/Sirt1-related pathway. The present work demonstrates that HG/[6]-GR prevented DOX-induced cardiotoxicity via the cardiotonic effect and promoting myocardial energy metabolism through the LKB1/AMPKα/Sirt1 signalling pathway, which promotes mitochondrial energy metabolism and protects against CHF.

2.
Cell Immunol ; 349: 104046, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32057354

RESUMO

Uncontrolled activation of NLRP3 inflammasome initiates a series of human inflammatory diseases. Targeting NLRP3 inflammasome has attracted considerable attention in developing potential therapeutic interventions. Here, we reported that dehydrocostus lactone (DCL), a main component of Saussurea lappa from the traditional Chinese medicine, inhibited NLRP3 inflammasome-mediated caspase-1 activation and subsequent interleukin (IL)-1ß production in primary mouse macrophages and human peripheral blood mononuclear cells and exerted an inhibitory effect on NLRP3-driven inflammation. Mechanistically, DCL significantly blocked the ASC oligomerization, which is essential for the assembly of activated inflammasome. Importantly, in vivo experiments showed that DCL reduced IL-1ß secretion and peritoneal neutrophils recruitment in LPS-mediated inflammation mouse model, which is demonstrated to be NLRP3 dependent. These results suggest that DCL is a potent pharmacological inhibitor of NLRP3 inflammasome and may be developed as a therapeutic drug for treating NLRP3-associated diseases.

3.
Phytother Res ; 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-32026542

RESUMO

Cholestasis is a common manifestation of decreased bile flow in various liver diseases. It results in fibrosis and even cirrhosis without proper treatment. It is believed that a wide range of factors, including transporter dysfunction, oxidative stress, inflammatory damage, and immune disruption, can cause cholestasis. In recent years, natural products have drawn much attention for specific multiple-target activities in diseases. Many attempts have been made to investigate the anticholestatic effects of natural products with advanced technology. This review summarizes recent studies on the biological activities and mechanisms of recognized compounds for cholestasis treatment. Natural products, including various flavonoids, phenols, acids, quinones, saponins, alkaloids, glycosides, and so on, function as comprehensive regulators via ameliorating oxidative stress, inflammation, and apoptosis, restoring bile acid balance with hepatic transporters, and adjusting immune disruption. Moreover, in this progress, nuclear factor erythroid 2-related factor 2, reactive oxygen species production, heme oxygenase-1, NF-κB, cholesterol 7 alpha-hydroxylase, and farnesoid X receptors are thought as main targets for the activity of natural products. Therefore, this review presents the detailed mechanisms that include multiple targets and diverse signalling pathways. Natural products are the valuable when seeking novel therapeutic agents to treat cholestatic liver diseases.

4.
Pharmacol Res ; 152: 104618, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31891789

RESUMO

Several decades have passed since resveratrol (RSV) was first identified in red wine. Researchers have reported the pleiotropic anti-oxidant, anti-inflammatory, anti-cancer, anti-aging, and neuronal protective effects of resveratrol and its glycosylated derivative. However, few studies have distinguished the minute differences in the properties between resveratrol and its glycosylated derivative in terms of synaptic plasticity. As an abundant natural product of glycosylated resveratrol, the derivative 2,3,4',5-tetrahydroxystilbene-2-O-ß-d-glucoside (TSG) has been determined to be a better option for long-term potentiation (LTP) in the hippocampus under physiological and pathological conditions than resveratrol. TSG, as well as its parent molecule RSV, could elicit early-LTP and recover fast excitatory postsynaptic potentials (EPSPs) in the hippocampus. Using various modalities, including pre- and post-whole-cell patch clamping techniques in the calyx of Held, pharmacological inhibition of the N-methyl-d-aspartic acid receptor (NMDAr) and the α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor (AMPAr) as well as protein kinase C (PKC) activation, we demonstrated that TSG, unlike RSV, could merely promote NMDA-mediated EPSC via PKCß cascade. Our results provide new knowledge that glycosylation of resveratrol could significantly improve its specificity in promoting sole NMDAr mediation of EPSPs, in addition to improving solubility and resistance against oxidation in vivo. These observations could contribute to further exploration of pharmaceutical evaluation of glycosylated stilbene in the future.

5.
Arch Toxicol ; 94(1): 245-256, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31630224

RESUMO

Idiosyncratic drug-induced liver injury (IDILI) is a rare but potentially severe adverse drug reaction. To date, identifying individuals at risk for IDILI remains challenging. This is a prospective study, where a nested case-control (1:5) design was adopted. For six patients who had abnormalities in liver function test after Polygonum multiflorum Thunb. (PM) ingestion (susceptible group), 30 patients with normal liver function were matched (tolerant group). Based on liquid chromatography-mass spectrometry, metabolomics analysis was done on serum samples prior to PM ingestion, to screen the differential metabolites and characterize metabolomic profiles of patient serum in the two groups. Multivariate analysis showed that there were remarkable separations between susceptible and tolerant groups. A total of 25 major differential metabolites were screened out, involving glycerophospholipid metabolism, sphingolipid metabolism, fatty acid metabolism, histidine metabolism and aromatic amino acid metabolism. Wherein, the area under the curve of the receiver operating characteristic curves of metabolites PE 22:6, crotonoyl-CoA, 2E-tetradecenoyl-CoA, phenyllactic acid, indole-5,6-quinone, phosphoribosyl-ATP were all greater than 0.9. The overall serum metabolic profile comprising of 25 metabolites could clearly distinguish susceptible and tolerant groups. This proof-of-concept study used metabolomics to characterize the metabolic profile of IDILI risk individuals before drug ingestion for the first time. The metabolome characteristics in patient serum before PM ingestion may predict the risk of liver injury after PM ingestion.

6.
J Pharm Pharmacol ; 72(2): 279-293, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31743450

RESUMO

OBJECTIVES: This study was aimed to explore the mechanism of Aconiti Lateralis Radix Praeparata (ALRP) and Zingiberis Rhizoma (ZR) on doxorubicin (DOX)-induced chronic heart failure (CHF) in rats by integrated approaches. METHODS: Effects of ALRP and ZR on cardiac function, serum biochemical indicators and histopathology in rats were analysed. Moreover, UHPLC-Q-TOF/MS was performed to identify the potential metabolites affecting the pathological process of CHF. Metabolomics and network pharmacology analyses were conducted to illustrate the possible pathways and network in CHF treatment. The predicted gene expression levels in heart tissue were verified and assessed by RT-PCR. KEY FINDINGS: ALRP-ZR demonstrated remarkable promotion of hemodynamic indices and alleviated histological damage of heart tissue. Metabolomics analyses showed that the therapeutic effect of ALRP and ZR is mainly associated with the regulation of eight metabolites and ten pathways, which may be responsible for the therapeutic efficacy of ALRP-ZR. Moreover, the results of RT-PCR showed that ALRP-ZR could substantially increase the expression level of energy metabolism-related genes, including PPARδ, PPARγ, Lpl, Scd, Fasn and Pla2g2e. CONCLUSIONS: The results highlighted the role of ALRP-ZR in the treatment of CHF by influencing the metabolites related to energy metabolism pathway via metabolomics and network pharmacology analyses.

7.
Zhongguo Zhong Yao Za Zhi ; 44(19): 4272-4276, 2019 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-31872709

RESUMO

In this paper,the case reports on rug-induced liver injury( ADR cases) related to Gukang Capsules containing Psoralea corylifolia( Buguzhi,BGZ) were collected from the adverse reaction monitoring database from January 1,2012 to December 31,2016,and the in-patients cases with drug-induced liver injury admitted to a tertiary Class A liver disease hospital from January 1,2010 to December 31,2016 were also collected. These collected cases were re-evaluated and analyzed. 110 cases with liver injury related to this preparation were collected from adverse reaction monitoring database,and 55 cases of them received the preparation alone,mainly for fracture treatment( 52. 74%). Ninty one cases( 82. 72%) met the standard of the biochemical diagnostic criteria for drug-induced liver injury. 89. 01% of patients were over the age of 41 and women accounted for 60. 9%. The time from administration to liver injury was 1-208 days,with the median of 29 d. The dose of the preparation was 2. 4-4. 8 g per day,with a cumulative dose ranging from 3. 6-699. 6 g. The recovery and improvement rate reached 96. 70% after positive treatment. Seven inpatient cases related to the preparation were collected in a tertiary Class A liver disease hospital,6 females and 1 male. All of them were over 40 years old. Two cases reached the " suspicious diagnosis" standard and 5 cases reached the " clinical diagnosis" standard in Guidelines for the diagnosis and treatment of herb-induced liver injury. Six patients had a good prognosis effect,but another one had liver failure. This preparation is commonly used in fracture,osteoarthritis and other diseases,with remarkable curative effect. However,ADR cases and hospital cases all indicated the risk of liver injury. There was no significant correlation between the time and dose of drug use and the occurrence of liver injury.The induced-liver injury may have immunological heterogeneity,thus regular monitoring of liver function should be taken during clinical use.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Medicamentos de Ervas Chinesas , Adulto , Bases de Dados Factuais , Feminino , Humanos , Masculino
8.
Front Pharmacol ; 10: 1135, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31680945

RESUMO

Backgrounds: Salsolinol (SAL), a plant-based isoquinoline alkaloid, was initially isolated from Aconiti Lateralis Radix Praeparata (ALRP) and identified as the active cardiotonic component of ALRP. This study was aimed to explore the therapeutic effect and mechanism by which SAL attenuates doxorubicin (DOX)-induced chronic heart failure (CHF) in rats and improves mitochondrial function in H9c2 cardiomyocytes. Methods: Rats were intraperitoneally injected with DOX to establish CHF model. Therapeutic effects of SAL on hemodynamic parameters, serum indices, and the histopathology of the heart were analyzed in vivo. Moreover, H9c2 cardiomyocytes were pretreated with SAL for 2 h before DOX treatment in all procedures in vitro. Cell viability, cardiomyocyte morphology, proliferation, and mitochondrial function were detected by a high-content screening (HCS) assay. In addition, a Seahorse Extracellular Flux (XFp) analyzer was used to evaluate the cell energy respiratory and energy metabolism function. To further investigate the potential mechanism of SAL, relative mRNA and protein expression of key enzymes in the tricarboxylic acid cycle in vivo and mitochondrial calcium uniporter (MCU) signaling pathway-related molecules in vitro were detected. Results: The present data demonstrated the pharmacological effect of SAL on DOX-induced CHF, which was through ameliorating heart function, downregulating serum levels of myocardial injury markers, alleviating histological injury to the heart, increasing the relative mRNA expression levels of key enzymes downstream of the tricarboxylic acid cycle in vivo, and thus enhancing myocardial energy metabolism. In addition, SAL had effects on increasing cell viability, ameliorating DOX-induced mitochondrial dysfunction, and increasing mitochondrial oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) in H9c2 cardiomyocyte. Moreover, we found that SAL might have an effect on improving mitochondrial respiratory function and energy metabolism via inhibiting excessive activation of MCU pathway in H9c2 cells. However, the protective effect could be ameliorated by ruthenium red (an MCU inhibitor) and abrogated by spermine (an MCU activator) in vitro. Conclusion: The therapeutic effects of SAL on CHF are possibly related to ameliorating cardiomyocyte function resulting in promotion of mitochondrial respiratory and energy metabolism. Furthermore, the potential mechanism might be related to downregulating MCU pathway. These findings may provide a potential therapy for CHF.

9.
Arch Toxicol ; 93(12): 3585-3599, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31677073

RESUMO

The occurrence of idiosyncratic drug-induced liver injury (IDILI) is a leading cause of post-marketing safety warnings and withdrawals of drugs. Carbamazepine (CBZ), widely used as an antiepileptic agent, could cause rare but severe idiosyncratic liver injury in humans. Although recent studies have shown that inflammasome is implicated in CBZ-induced hepatocellular injury in vitro, the precise pathogenesis of hepatotoxicity remains largely unexplored. Here we report that CBZ causes idiosyncratic liver injury through promoting specific stimuli-induced NLRP3 inflammasome activation. CBZ (40 µM) enhances NLRP3 inflammasome activation triggered by adenosine triphosphate (ATP) or nigericin, rather than SiO2, monosodium urate crystal or intracellular lipopolysaccharide (LPS). In addition, CBZ has no effect on NLRC4 or AIM2 inflammasome activation. Mechanistically, synergistic induction of mitochondrial reactive oxygen species (mtROS) is a crucial event in the enhancement effect of CBZ on ATP- or nigericin-induced NLRP3 inflammasome activation. Moreover, the "C=C" on the seven-membered ring and "C=O" on the nitrogen of CBZ may be contribute to NLRP3 inflammasome hyperactivation and hepatotoxicity. Notably, in vivo data indicate that CBZ (50 mg/kg) causes liver injury in an LPS (2 mg/kg)-mediated susceptibility mouse model of IDILI, accompanied by an increase in caspase-1 activity and IL-1ß production, whereas the combination of CBZ and LPS does not exhibit the effect in NLRP3-knockout mice. In conclusion, CBZ specifically promotes ATP- or nigericin-induced NLRP3 inflammasome activation and causes idiosyncratic liver injury. Our findings also suggest that CBZ may be avoided in patients with NLRP3 inflammasome activation-related diseases that are triggered by ATP or nigericin, which may be risk factors for IDILI.

10.
Front Pharmacol ; 10: 1326, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31780942

RESUMO

Introduction: Use of herbal medicines (HMs) is widespread across the world, with many people relying on HMs for their primary healthcare or using HMs in the context of a healthy life style. HMs originate from plant material and, as such, are often seen as "natural" and believed to be (relatively) safe by patients. Hepatobiliary disorders have been associated with numerous HMs. Aim: This paper aims to analyze reporting patterns for hepatobiliary disorders associated with HMs use from reports submitted to the WHO global database of individual case safety reports (ICSRs) VigiBase. Methods: A data extraction in VigiBase, the WHO international database of ICSR reports, was performed by the Uppsala Monitoring Centre on 2019-01-16. The dataset contained all ICSRs where an HM was identified with the UMC-assigned ATC code "V90: unspecified herbal and traditional medicine" and where the HM was classified as being either the suspected drug or an interacting drug, and containing at least one adverse reaction in the MedDRA® System Organ Class (SOC) Hepatobiliary Disorders (HBD). Descriptive analyses in Excel 2013® were used to determine general characteristics of the reports in the broad data set, including total number of reports, reporting country and patient characteristics. For single suspect herbal reports, reports categorized as "serious" according to CIOMS criteria (CIOMS), 2001) were extracted. Results: In total, 2,483 reports describing with at least one ADR in the SOC HBD were extracted from VigiBase. In total, 780 (31.4%) reports concern only one suspect HM. However, for 188 reports of these reports (24.1%), the single suspect herbal preparation contains more than one herbal ingredient. The 592 reports for single suspect herbal preparations described a total of 764 ADRs in the SOC HBD. Jaundice was the most reported ADR for these reports. Conclusion: Almost 2,500 reports for HMs and with at least one ADR coded to the MedDRA® SOC HBD were retrieved from VigiBase. Of the HBD SOC HM reports, around 25% concerned a single herbal species as the suspect "drug." Substantial issues with coding of the suspect herbal drugs were found. In-depth causality assessment of the cases is needed to draw conclusions on the strength of the relationships.

11.
Zhongguo Zhong Yao Za Zhi ; 44(16): 3435-3440, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31602906

RESUMO

The aim of this paper was to investigate the anti-inflammatory effect of Tripterygium wilfordii processed with licorice on DSS-induced ulcerative colitis( UC) mice and its regulation on intestinal immune system. In this study,a DSS-induced animal model of UC mice was established,with mesalazine( Mes) as a positive drug. The pharmacodynamic effects of low( PT1) and high( PT2)doses of T. wilfordii processed with licorice were analyzed by disease activity index( DAI),colon length and colon histopathological score in mice. By detecting the expression levels of TNF-α and IL-6 cytokines in the serum of mice,immunohistochemical CD3+T and Fox P3+Treg staining in the colon of mice,the anti-inflammatory and immunoregulatory effects of T. wilfordii processed with licorice on UC mice were analyzed. The hepatotoxicity of each dose of T. wilfordii processed with licorice was also analyzed by HE staining in liver tissue of mice and ALT and AST levels in serum. The results showed that the colitis symptoms of the mice in the PT1 group and the PT2 group were alleviated,the inflammatory cell infiltration was reduced. And the expression of inflammatory factors was decreased,the difference was statistically significant compared with the model group( P<0. 05). The HE staining and ALT and AST levels in the high dose group and low dose group were not significantly different from those in the normal group. The results showed that T. wilfordii processed with licorice has the anti-inflammatory and immunomodulatory effects on UC mice,and the dose did not show significant hepatotoxicity.


Assuntos
Anti-Inflamatórios/farmacologia , Colite Ulcerativa/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Glycyrrhiza/química , Tripterygium/química , Animais , Sulfato de Dextrana , Camundongos , Extratos Vegetais/farmacologia
12.
Zhongguo Zhong Yao Za Zhi ; 44(16): 3454-3459, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31602909

RESUMO

The present study was aimed to explore the dose-toxicity-effect relationship of Tripterygium wilfordii Hook f( TW) processed by liquorice,to establish the safe and effective therapeutic window,and further to provide scientific reference for the clinical use of TW. The toxicity and anti-inflammatory effect of six doses of raw TW and TW processed by liquorice( 0. 78,1. 56,3. 12,6. 24,12. 48,15. 60 g·kg-1) in 1-fluoro-2,4-dinitrobenzene( DNFB)-induced allergic contact dermatitis( ACD) model were mainly examined by histopathology and serum biochemistry. The liver biochemical parameters including ALT and AST,related inflammatory factors including TNF-α and IL-2,together with liver index,kidney index and the other pharmacodynamic indicators,were examined and compared. The results showed that compared with the control group,the serum levels of TNF-α and IL-2 of the model group were significantly increased( P<0. 01),which proved that the ACD model was successful. The comprehensive analysis of liver biochemical indexes,serum inflammatory factors and the other indexes showed that the safe and effective therapeutic window of TW processed by liquorice was 3. 12-12. 48 g·kg-1. The results showed the therapeutic window of TW processed by liquorice was much broader than that of raw TW. And it could provide scientific reference for the clinical rational use of TW.


Assuntos
Dermatite Alérgica de Contato/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Glycyrrhiza/química , Extratos Vegetais/farmacologia , Tripterygium/química , Animais , Citocinas/sangue
13.
Hepatology ; 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31609008

RESUMO

We have read the article by Han et al. (1) and would like to express our concerns for the interpretation of this study. As reported by the authors, hepatocellular carcinoma (HCC) was observed in mice after exposure to aristolochic acids (AAs) alone or a combination of AAs and carbon tetrachloride.

14.
Acta Pharm Sin B ; 9(4): 734-744, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31384534

RESUMO

Aberrant activation of NLRP3 inflammasome has been implicated in the pathogenesis of diverse inflammation-related diseases, and pharmacological molecules targeting NLRP3 inflammasome are of considerable value to identifying potential therapeutic interventions. Cardamonin (CDN), the major active ingredient of the traditional Chinese medicinal herb Alpinia katsumadai, has exerted an excellent anti-inflammatory activity, but the mechanism underlying this role is not fully understood. Here, we show that CDN blocks canonical and noncanonical NLRP3 inflammasome activation triggered by multiple stimuli. Moreover, the suppression of CDN on inflammasome activation is specific to NLRP3, not to NLRC4 or AIM2 inflammasome. Besides, the inhibitory effect is not dependent on the expression of NF-κB-mediated inflammasome precursor proteins. We also demonstrate that CDN suppresses the NLRP3 inflammasome through blocking ASC oligomerization and speckle formation in a dose-dependent manner. Importantly, CDN improves the survival of mice suffering from lethal septic shock and attenuates IL-1ß production induced by LPS in vivo, which is shown to be NLRP3 dependent. In conclusion, our results identify CDN as a broad-spectrum and specific inhibitor of NLRP3 inflammasome and a candidate therapeutic drug for treating NLRP3 inflammasome-driven diseases.

15.
Xenobiotica ; : 1-11, 2019 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-31424332

RESUMO

Polygonum multiflorum Thunb. (PM) is a famous traditional Chinese medicine with liver tonic effect, but arousing great concerns for hepatotoxicity issue. In this study, we elucidated the contribution of the two major compounds, emodin-8-O-ß-D-glucoside (EG) and 2,3,5,4´-tetrahydroxyl diphenylethylene-2-O-glucoside (TSG), in PM-induced liver injury. Based on LC-MS, the two concerned compounds were detected simultaneously in the sera of patients with PM-induced liver injury. In the lipopolysaccharide (LPS)-mediated inflammatory stress rat model, by the analysis of plasma biochemistry and liver histopathology, we observed that the solo treatment of EG, not TSG, could induce significant liver injury; and the combined administration of EG and TSG caused more severe liver injury than that of EG. Metabolomics analysis revealed that the EG-triggered liver injury was associated with significant disturbances of sphingolipids and primary bile acids metabolism pathways. In the combined administration group, much more disturbances in EG-triggered metabolic pathways, as well as alterations of several additional pathways such as retinol metabolism and vitamin B6 metabolism, were observed. Taken together, we considered EG was involved in the idiosyncratic liver injury of PM, and TSG played a synergetic role with EG, which contributed to the understanding of the hepatotoxic basis of PM.

16.
AMB Express ; 9(1): 101, 2019 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-31297618

RESUMO

Antibiotics abuse has caused increased bacterial resistance, which severely limits the application of antibiotics to the treatment of bacterial infections. Therefore, it is urgent to develop new antibacterial drugs through other sources. Dracontomelon dao (Blanco) Merr. & Rolfe (Ren Mianzi in Chinese) is a traditional medicinal material derived from Anacardiaceae with a long history of treating various infectious diseases, such as decubitus and skin ulcers. Recent research has indicated that different extracts from the leaves of D. dao, especially the ethyl acetate (EtOAc) fraction containing flavonoids and phenolic acids, exhibit potent antibacterial activities. In this research, the combined anti-drug-resistant bacterial activities of these active ingredients were investigated. Six samples (S1-S6) were obtained from the EtOAc fraction of D. dao leaves. Microcalorimetric measurements and principal component analysis were performed on the in vitro samples. The results showed that all six samples had notable antibacterial activities. Specifically, sample S6 exhibited a prominent antibacterial effect, with an IC50 value of 84.3 µg mL-1, which was significantly lower than that of other samples. The relative contents of main flavonoids and phenolic acids in S6 sample were confirmed by UPLC/Q-TOF-MS. In conclusion, sample S6 from the EtOAc fraction of D. dao leaves could be used as a potential antimicrobial resource in the treatment of infectious diseases. This work provides an insight into the effect of traditional Chinese medicine on drug-resistant bacteria. Moreover, the purification and characterization of the chemical compounds from the sample S6 deserve further analysis.

17.
Zhongguo Zhong Yao Za Zhi ; 44(9): 1921-1926, 2019 May.
Artigo em Chinês | MEDLINE | ID: mdl-31342722

RESUMO

In the present study,non-targeted metabolomics technique was used to screen potentially susceptibility biomarkers in patients with mild liver function abnormalities during long-term use of Chinese herbal compound. According to the inclusion and exclusion criteria,we collected 7 cases of patients with abnormal liver function during the period of complete taking Chinese herbal medicine( 60 days),and 18 cases of patients with normal liver function in re-examination from the reproductive medicine center in our hospital. Ultra performance liquid chromatography coupled with time-of-flight mass spectrometry( UPLC-Q-TOF/MS~E) technique combined with Progenesis QI software was used to analyze the differential biomarkers in serum of patients with wild liver function abnormalities and normal liver function. 11 potential biomarkers such as bilirubin,pantothenic acid,hippuric acid,sphingomyelin,palmitic acid,and oleic acid were tentatively identified. Metabolic disorders in patients with herbal-induced mild liver abnormality were mainly related to two pathways: pantothenic acid and coenzyme A biosynthesis and linoleic acid metabolism. It could provide a reference for the early warning of mild liver function abnormalities of patients that may be caused by long-term use of Chinese medicine compound in clinical application,and will lay a foundation for further understanding the endogenous substance changes in different levels of liver injury.


Assuntos
Medicamentos de Ervas Chinesas/efeitos adversos , Hepatopatias/sangue , Metabolômica , Biomarcadores/sangue , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Espectrometria de Massas
18.
Artigo em Inglês | MEDLINE | ID: mdl-31341490

RESUMO

Panax ginseng (PG) is a widely used functional food and herbal with immunoregulation activity. Currently, immunoregulation studies of PG mainly focused on the specific actions of individual constituents. However, the integral immunoregulation mechanisms of PG need further research. In this study, an integrated metabolomics and network pharmacology approach were used to investigate it. High-content screening was used to evaluate macrophage phagocytosis activity of PG. Untargeted metabolomics profiling of murine macrophage cells with UHPLC-Q-TOF-MS and a multivariate data method were performed to discover the potential biomarkers and metabolic pathways. Then, a macrophage phenotype related "ingredients-targets-metabolites" network of PG was constructed using network pharmacology for further research. As a result, PG can significantly enhance macrophage phagocytosis of GFP-E. coli. A total of twenty potential biomarkers and ten main pathways for which levels changed markedly upon treatment were identified, including glycerophospholipid metabolism, glutathione metabolism, choline metabolism, and taurine metabolism. Twenty compounds of PG associated with metabolomic changes were selected by the network pharmacology analysis, including ginsenoside Re, ginsenoside Rg1, frutinone A, and kaempferol. The network pharmacology results also showed that PG can polarize macrophages to both M1 and M2 phenotype but may be prone to M2 phenotype. In conclusion, our results indicated that PG may be prone to polarize macrophages to M2 phenotype by mainly regulating the glutathione and choline metabolism, which was related to twenty compounds of PG.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA