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1.
Eur J Med Chem ; 182: 111652, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31494470

RESUMO

Farnesoid X receptor (FXR) is a key regulator in charge of bile acid synthesis, transport, and metabolism. Activation of FXR represses bile acid synthesis and increases its excretion and transport, consequently protecting the liver functions. Thus, FXR is considered as a critical therapeutic target of cholestasis and nonalcoholic steatohepatitis. Herein, we isolated and identified fourteen new protostane-type triterpenoids (1-14) and four known analogues (15-18) from Alisma orientale, and finally constructed a small library of protostane-type triterpenoids (1-70) to investigate their structure-activity relationship with FXR, further leading to obtain compound 15 with potent agonistic activity against FXR (EC50 = 90 nM). Extensive in vitro investigation confirmed high efficacy of compound 15 against FXR in living cell, and revealed its underlying mechanism for FXR activation (amino acid residues Arg331 and Ser332) by molecular docking and site-directed mutagenesis technology.


Assuntos
Produtos Biológicos/farmacologia , Receptores Citoplasmáticos e Nucleares/agonistas , Terpenos/farmacologia , Alisma/química , Produtos Biológicos/química , Produtos Biológicos/isolamento & purificação , Células Cultivadas , Relação Dose-Resposta a Droga , Células Hep G2 , Humanos , Simulação de Acoplamento Molecular , Estrutura Molecular , Mutagênese Sítio-Dirigida , Receptores Citoplasmáticos e Nucleares/genética , Relação Estrutura-Atividade , Terpenos/química , Terpenos/isolamento & purificação
2.
J Med Food ; 22(10): 1067-1077, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31403348

RESUMO

To reduce microbial loads in medicinal herbs, Cnidii Rhizoma and Alismatis Rhizoma were subjected to electron-beam (e-beam) irradiation at doses (≤10 kGy) as permitted by the Korean Food Code. The effects of e-beam irradiation on the microbial load, stability of the active components, and anti-inflammatory activity of medicinal herbs were determined. We observed that the total aerobic bacteria (TAB; 4.0-7.0 log CFU/g), yeasts and molds (Y&M; 3.3-6.8 log CFU/g), and coliform counts (CC; 3.2-3.8 log CFU/g) in both herb samples were effectively reduced in a dose-dependent manner, resulting in acceptable levels of <3.0 log CFU/g in TAB and Y&M and negative in CC at 10 kGy irradiation. The concentration of the active components (0.87-4.22 mg/g) of Cnidii Rhizoma, including z-ligustilide, chlorogenic acid, senkyunolide A, and ferulic acid, in order of prevalence and those (0.86-2.76 mg/g) of Alismatis Rhizoma, including Alisol B acetate and Alisol B, were not changed at irradiation doses of ≤10 kGy. The extracts of e-beam irradiated Cnidii Rhizoma and Alismatis Rhizoma showed a reduced production of inflammation-related factors, such as nitric oxide, prostaglandin E2, interleukin (IL)-1ß, and IL-6, in a concentration-dependent manner, which was induced by lipopolysaccharide in RAW 264.7 cell. However, there was no significant difference observed at e-beam irradiation doses of 0, 1, 5, and 10 kGy. Thus, we confirm that e-beam irradiation up to 10 kGy was effective for the control of microbial load in Cnidii Rhizoma and Alismatis Rhizoma without causing considerable changes in their major active components and anti-inflammatory activity. The results show the potential of e-beam application for sanitization of medicinal herbs.


Assuntos
Alisma/química , Anti-Inflamatórios/química , Apiaceae/química , Carga Bacteriana , Rizoma/química , Alisma/microbiologia , Alisma/efeitos da radiação , Animais , Anti-Inflamatórios/farmacologia , Apiaceae/microbiologia , Apiaceae/efeitos da radiação , Dinoprostona/metabolismo , Elétrons , Interleucinas/metabolismo , Camundongos , Óxido Nítrico/metabolismo , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Plantas Medicinais/química , Plantas Medicinais/microbiologia , Plantas Medicinais/efeitos da radiação , Células RAW 264.7 , Rizoma/microbiologia , Rizoma/efeitos da radiação
3.
Zhongguo Zhong Yao Za Zhi ; 44(9): 1729-1733, 2019 May.
Artigo em Chinês | MEDLINE | ID: mdl-31342693

RESUMO

To establish a quality constant evaluation system of Alismatis Rhizoma decoction pieces,in order to provide reference for regulating the market circulation of this decoction pieces. A total of 18 batches of Alismatis Rhizoma decoction pieces were collected from different pharmaceutical factories,and the morphological parameters of each sample were tested. The content of alisol B 23-acetate in Alismatis Rhizoma decoction pieces was determined by HPLC in the 2015 edition of Chinese Pharmacopoeia,and the parameters such as quality constant and relative quality constant were calculated. The quality constant range of 18 batches of Alismatis Rhizoma decoction pieces was 0. 390-2. 076. If 18 batches of Alismatis Rhizoma decoction pieces were divided into 3 grades,taking 80% of the maximum quality constant as first grade,50% to 80% as second grade,and the rest as third grade,then the quality constant of firstgrade samples was ≥1. 66,the quality constant of second-grade samples was ≥1. 04 and <1. 66,and the quality constant of third-grade samples was <1. 04. The established quality constant evaluation method is objective and feasible,which can be used to classify the grade of Alismatis Rhizoma decoction pieces and provide a reference method to control the quality of this decoction pieces.


Assuntos
Alisma/química , Medicamentos de Ervas Chinesas/normas , Cromatografia Líquida de Alta Pressão , Controle de Qualidade , Rizoma/química
4.
Artigo em Inglês | MEDLINE | ID: mdl-31271908

RESUMO

Alisma plantago-aquatica is known to regulate water and fluid balance in cells, and is under testing for the therapy for patients suffering from chronic nephritis. Herein, a UHPLC-MS/MS method was established and validated for the determination of six bioactive triterpenoids of raw and salt-processed Alisma plantago-aquatica in rat plasma. The acquired plasma was subjected to protein precipitation with acetonitrile. Glycyrrhetinic acid was employed as internal standard. The pretreated samples were separated on a reversed phased column with a mobile phase of acetonitrile and water (including 0.1% formic acid). The MRM mode for the six triterpenoids were at m/z 535.4 → 489.4 for alisol A, m/z 517.3 → 471.4 for alisol B, m/z 533.3 → 487.3 for alisol F, m/z 577.4 → 531.4 for alisol A-24-acetate, m/z 559.4 → 495.4 for alisol B-23-acetate, m/z 573.3 → 509.3 for alisol C-23-acetate, and 469.3 → 425.3 for the IS. The accuracy and precision of the method were determined as -2.2%-3.6% and 0.8%-3.0%, respectively. This approach was employed to a pharmacokinetic study of the six bioactive triterpenoids after intragastric administration of raw and processed Alisma plantago-aquatica in rats. The two-phasic pharmacokinetic of alisol B, alisol C-23-acetate and alisol F were reported for the first time, which may be ascribed to enterohepatic recirculation of these triterpenoids.


Assuntos
Alisma/química , Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/análise , Medicamentos de Ervas Chinesas/farmacocinética , Espectrometria de Massas em Tandem/métodos , Triterpenos/sangue , Triterpenos/farmacocinética , Animais , Masculino , Ratos , Ratos Sprague-Dawley
5.
BMC Complement Altern Med ; 19(1): 92, 2019 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-31035991

RESUMO

BACKGROUND: To investigate the effects of the Alisma and Rhizoma decoction on nonalcoholic steatohepatitis (NASH) and to further shed light on the underlying mechanisms of the actions of the Alisma and Rhizoma decoction. METHODS: Plasma alanine aminotransferase (ALT) content was determined and liver inflammation and fibrosis were evaluated. Intrahepatocellular malondialdehyde and superoxide dismutase contents were determined using commercially available kits Furthermore, α-SMA expression in liver tissues was examined by immunohistochemistry and LC3-II was detected by immunoblotting assays. RESULTS: Mice receiving the Alisma and Rhizoma decoction by gastric lavage had significantly lower plasma ALT content and markedly higher hepatic superoxide dismutase activity than mice receiving the methionine-choline deficient (MCD) diet. Furthermore, the decoction aborted MCD-induced increase in liver malondialdehyde content. Immunohistochemistry showed that the decoction suppressed hepatic α-SMA expression. Our transmission electronic microscopy revealed that the decoction markedly reduced the number of autophagosomes and immunoblotting assays showed that the decoction caused a dose-dependent decrease in LC3-II in hepatic tissues. CONCLUSION: The Alisma and Rhizoma decoction lessens NASH-associated liver injuries by modulating oxidative stress and autophagy in hepatocytes of mice fed with MCD.


Assuntos
Alisma/química , Atractylodes/química , Autofagia/efeitos dos fármacos , Hepatopatia Gordurosa não Alcoólica/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Animais , Modelos Animais de Doenças , Masculino , Camundongos , Camundongos Endogâmicos C57BL
6.
Zhongguo Zhong Yao Za Zhi ; 44(5): 942-947, 2019 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-30989853

RESUMO

To research the correlation between accumulation of triterpenoids and expression of key enzymes genes in triterpenoid biosynthesis of Alisma orientale,the study utilized UPLC-MS/MS method to detect eight triterpenoids content in the tuber of A. orientale from different growth stages,including alisol A,alisol A 24 acetate,alisol B,alisol B 23 acetate,alisol C 23 acetate,alisol F,alisol F 24 acetate and alisol G,and then the Real time quantitative PCR was used to analyze the expression of key enzymes genes HMGR and FPPS in triterpenoid biosynthesis. Correlation analysis showed that there was a significant positive relation between the total growth of these eight triterpenoids and the average relative expression of HMGR and FPPS(HMGR: r = 0. 998,P<0. 01; FPPS: r = 0. 957,P<0. 05),respectively. Therefore,the study preliminarily determined that HMGR and FPPS genes could regulate the biosynthesis of triterpenoids in A. orientale,which laid a foundation for further research on the biosynthesis and regulation mechanism of triterpenoids in A. orientale.


Assuntos
Alisma/química , Alisma/genética , Geraniltranstransferase/genética , Triterpenos/análise , Cromatografia Líquida , Hidroximetilglutaril-CoA-Redutases NADP-Dependentes/genética , Compostos Fitoquímicos/análise , Extratos Vegetais , Proteínas de Plantas/genética , Tubérculos/química , Espectrometria de Massas em Tandem
7.
Int J Biol Macromol ; 133: 184-189, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-30991064

RESUMO

As a part of our searching for natural human carboxylesterase 2 (human CES 2) inhibitors from traditional Chinese medicine, we found that the extract of Alisma orientale significantly inhibited human CES 2 in vitro. The investigation on A. orientale led to the isolation of a new protostane-type triterpenoid alismanin I (1). Its structure was determined according to HRESIMS, 1D and 2D NMR spectra. Alismanin I (1) displayed significantly inhibitory activity against human CES 2 with IC50 value of 1.31 ±â€¯0.09 µM assayed by human CES 2-mediated DDAB hydrolysis. According to its inhibition kinetic result, compound 1 was a noncompetitive type inhibitor, and its Ki was 3.65 µM. Its inhibitory effect was confirmed in living cell level through a visual manner. The potential interaction mechanism of compound 1 with human CES 2 was also analyzed by circular dichroism (CD) spectrum and molecular docking.


Assuntos
Alisma/química , Carboxilesterase/antagonistas & inibidores , Carboxilesterase/metabolismo , Inibidores Enzimáticos/farmacologia , Simulação de Acoplamento Molecular , Extratos Vegetais/farmacologia , Carboxilesterase/química , Domínio Catalítico , Dicroísmo Circular , Inibidores Enzimáticos/metabolismo , Humanos , Cinética , Extratos Vegetais/metabolismo
8.
Nat Prod Res ; 33(21): 3083-3088, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30427740

RESUMO

A new protostane-type triterpenoid bearing an oxetane ring in the side-chain, named alisol W (1), has been obtained from the dried rhizome of Alisma plantago-aquatica subsp. orientale. The structure and absolute configuration of compound 1 was determined from extensive spectroscopic analysis. In addition, the vasorelaxant activity and the inhibition on 11ß-HSD1 of compound 1 were also evaluated, however, it didn't show remarkable effects.


Assuntos
Alisma/química , Triterpenos/isolamento & purificação , 11-beta-Hidroxiesteroide Desidrogenase Tipo 1/antagonistas & inibidores , Humanos , Estrutura Molecular , Rizoma/química , Análise Espectral , Triterpenos/química , Vasodilatadores/análise
9.
Nat Prod Res ; 33(6): 776-781, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29183156

RESUMO

A new protostane-type triterpenoid, 5ß,29-dihydroxy alisol A (1) was isolated from Alisma plantago-aquatica subsp. orientale (Sam.) Sam. as well as 12-deoxyphorbol-13α-pentadecanoate (2). We first report the presence of compound 2 in the genus Alisma. Their structures were established on the basis of 1D and 2D NMR, and HRESIMS spectroscopic analyses. All the isolated compounds were assayed for their inhibitory effects against human carboxylesterase 2 (HCE-2). Compounds 1 and 2 displayed inhibitory activities against HCE-2 with IC50 values of 29.2 and 4.6 µM, respectively. The interaction mechanisms of HCE-2 with compounds 1 and 2 were investigated by molecular docking, respectively.


Assuntos
Alisma/química , Carboxilesterase/antagonistas & inibidores , Colestenonas/farmacologia , Simulação de Acoplamento Molecular , Triterpenos/farmacologia , China , Colestenonas/isolamento & purificação , Humanos , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Rizoma/química , Triterpenos/isolamento & purificação
10.
Biochem Biophys Res Commun ; 505(4): 1015-1021, 2018 11 10.
Artigo em Inglês | MEDLINE | ID: mdl-30314700

RESUMO

Alisol B-23-acetate (AB23A), a tetracyclic triterpenoid isolated from the rhizome of Alisma orientale, has been reported to exert anti-proliferative activities in human colon, ovarian and gastric cancer cells. However, the anti-cancer effect of this compound on human lung cancer cells has not yet been thoroughly elucidated. In the present study, we investigated the effects of AB23A on the cell viability and apoptosis in human lung cancer A549 and NCI-H292 cells. The results indicated that AB23A inhibited the growth of A549 and NCI-H292 cells in dose- and time-dependent manner, however, there was only weak cytotoxicity on normal bronchial epithelial cells. The induction of apoptosis by AB23A was demonstrated by DAPI and annexin-V-FITC/PI staining. Further investigation revealed that AB23A decreased mitochondrial membrane potential (MMP) and up regulated reactive oxygen species (ROS) level. Meanwhile, the increased Bax/Bcl-2 ratio, activated caspase-3, caspase-9 and PARP were observed. In addition, AB23A increased the release of cytochrome c from mitochondria and the translocation of apoptotic inducing factor (AIF) into nuclei. Taken together, these results indicated that AB23A induced apoptosis by activating the intrinsic pathway, and suggested that AB23A can be used as a potential modulating agent in lung cancer.


Assuntos
Alisma/química , Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Colestenonas/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Mitocôndrias/efeitos dos fármacos , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Proliferação de Células/efeitos dos fármacos , Colestenonas/química , Colestenonas/isolamento & purificação , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Mitocôndrias/metabolismo , Conformação Molecular , Relação Estrutura-Atividade , Células Tumorais Cultivadas
11.
Int J Mol Sci ; 19(9)2018 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-30177620

RESUMO

CXC motif chemokine ligand 10 (CXCL10) and its receptor CXC motif chemokine receptor 3 (CXCR3), play important roles in the motility of breast cancer cells. Alisma canaliculatum is a herb that has been used as a traditional medicine for thousands of years in Korea and China. Whether A. canaliculatum inhibits the motility of metastatic breast cancer cells is not clear yet. In this study, we show that A. canaliculatum ethanolic extract (ACE) prevented tumor necrosis factor-alpha (TNFα)-induced migration of MDA-MB-231 cells. ACE significantly attenuated TNFα-induced upregulation of CXCL10 and CXCR3 expression at the gene promoter level. Mechanistically, ACE inhibits TNFα-induced phosphorylation of inhibitor of κB (IκB) kinase (IKK), IκB and p65/RelA, leading to the suppression of nuclear translocation of p65/RelA nuclear factor kappa-B (NF-κB). Also, ACE inhibited NF-κB-dependent CXCR3 and CXCL10 promoter activities. These results suggest that ACE abrogates TNFα-induced migration of MDA-MB-231 breast cancer cells through down-regulation of IKK-NF-κB-dependent CXCR3 and CXCL10 expression. Our results suggest that ACE has potential as a herbal supplement for the inhibition of breast cancer metastasis.


Assuntos
Alisma/química , Neoplasias da Mama/metabolismo , Quimiocina CXCL10/metabolismo , Etanol/química , NF-kappa B/metabolismo , Extratos Vegetais/uso terapêutico , Receptores CXCR3/metabolismo , Fator de Necrose Tumoral alfa/farmacologia , Linhagem Celular Tumoral , Feminino , Humanos , Extratos Vegetais/química , Transdução de Sinais/efeitos dos fármacos
12.
J Chromatogr A ; 1562: 1-11, 2018 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-29798805

RESUMO

Currently, nanosphere-based ligand fishing cannot be accomplished with imaging processing, although this step is important for real-time identification. Herein, a ligand fishing technique combined with real-time imaging is presented for the identification of ligands for heat shock protein 90α (Hsp 90α) from a complex matrix, Alisma plantago-aquatica Linn. crude extract, using Hsp 90α-functionalized mesoporous silica nanoparticle (MSN)-InP/ZnS quantum dot (QD) nanocomposites as a support material. Twenty ligands for Hsp 90α were screened, and their structures were identified by mass spectrometry. The activities of the ligands were verified by real-time imaging of cells apoptotic morphological changes. Quantitative analysis showed that Alisma plantago-aquatica Linn contained 8.19µg/g Alisol F, which regarded as one typical component of Alisma plantago-aquatica Linn, and the extraction ratio of Alisol F was 76.2%. The precision for five replicate measurements was 7.0% (RSD). The prepared nanocomposites were also used to screen proteins from a mixture of cellular extracts, and five proteins from HeLa cells were identified as potential client proteins of Hsp 90α.


Assuntos
Técnicas de Química Analítica/métodos , Proteínas de Choque Térmico HSP90/química , Índio/química , Nanocompostos/química , Fosfinas/química , Proteínas/análise , Dióxido de Silício/química , Sulfetos/química , Compostos de Zinco/química , Alisma/química , Células HeLa , Humanos , Ligantes , Pontos Quânticos/química , Triterpenos/análise
13.
Phytomedicine ; 45: 93-104, 2018 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-29705003

RESUMO

BACKGROUND: Quality control of traditional Chinese medicines is currently a great concern, due to the correlation between the quality control indicators and clinic effect is often questionable. According to the "multi-components and multi-targets" property of TCMs, a new special quality and bioactivity evaluation system is urgently needed. PURPOSE: Present study adopted an integrated approach to provide new insights relating to uncover quality marker underlying the effects of Alisma orientale (AO) on lipid metabolism. METHODS: In this paper, guided by the concept of the quality marker (Q-marker), an integrated strategies "effect-compound-target-fingerprint" was established to discovery and screen the potential quality marker of AO based on network pharmacology and chemical analysis. Firstly, a bioactivity evaluation was performed to screen the main active fractions. Then the chemical compositions were rapidly identified by chemical analysis. Next, networks were constructed to illuminate the interactions between these component and their targets for lipid metabolism, and the potential Q-marker of AO was initially screened. Finally, the activity of the Q-markers was validated in vitro. RESULTS: 50% ethanol extract fraction was found to have the strongest lipid-lowering activity. Then, the network pharmacology was used to clarify the unique relationship between the Q-markers and their integral pharmacological action. CONCLUSION: Combined with the results obtained, five active ingredients in the 50% ethanol extract fraction were given special considerations to be representative Q-markers: Alisol A, Alisol B, Alisol A 23-acetate, Alisol B 23-acetate and Alisol A 24-acetate, respectively. The chromatographic fingerprints based Q-marker was establishment. The integrated Q-marker screen may offer an alternative quality assessment of herbal medicines.


Assuntos
Alisma/química , Biomarcadores Farmacológicos/análise , Hipolipemiantes/farmacologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Extratos Vegetais/farmacologia , Animais , Colestenonas/análise , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Células Hep G2 , Humanos , Hipolipemiantes/química , Masculino , Medicina Tradicional Chinesa/normas , Extratos Vegetais/normas , Ratos Wistar
14.
Phytomedicine ; 42: 207-218, 2018 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-29655688

RESUMO

BACKGROUND: Tubulo-interstitial fibrosis (TIF) is the common pathway in the chronic kidney disease (CKD). Epithelial-to-mesenchymal transition (EMT) is a major contributor to the TIF by the increased myofibroblasts. Renin-angiotensin system (RAS) is critical mediator on EMT in progressive CKD. Angiotensin II (ANG) mediates EMT and causes TIF by stimulating transforming growth factor-ß1 (TGF-ß1). RAS activation could further activate TGF-ß1. Inhibition of the RAS is one of the most powerful therapies for progressive CKD. 25-O-methylalisol F (MAF) is a new tetracyclic triterpenoid compound isolated from the Alismatis rhizoma, which is extensively used for anti-hypertensive, diuretic and anti-hyperlipidemic effects. METHODS: Inhibitory effect of MAF on EMT is investigated in both TGF-ß1- and ANG-induced tubular epithelial cells (NRK-52E) and fibroblasts (NRK-49F). Western blot analysis, qRT-PCR, siRNA, immunofluorescence staining and co-immunoprecipitation techniques were used to evaluate the inhibition of MAF on EMT and further revealed the intervention effects on RAS, TGF-ß/Smad and Wnt/ß-catenin pathways. RESULTS: MAF treatment significantly inhibited TGF-ß1 and ANG-induced expressions of collagen I, fibronectin, α-SMA, vimentin and E-cadherin at both mRNA and protein levels in the NRK-52E and NRK-49F cells. The action mechanism revealed that MAF significantly ameliorated upregulation of angiotensinogen, renin, ACE and AT1R expressions. Further, MAF attenuated upregulation of Smad3 phosphorylation and downregulation of Smad7, but did not affect the phosphorylation of Smad2, PI3K, ERK1/2 and p38 expressions and Smad4 expression in NRK-52E cells. Co-immunoprecipitation analysis indicated that MAF selectively blocked the combination of Smad3 with TGFßRI and Smad3 with SARA without interfering with the Smad2, TGFßRI and SARA interaction. Additionally, MAF suppressed the expressions of Wnt1 and ß-catenin as well as its downstream target Snail1, Twist, MMP-7, PAI-1 and FSP1 expressions in NRK-52E cells. CONCLUSIONS: MAF simultaneously targeted multiple RAS components and it was a novel RAS inhibitor. MAF inhibited EMT by Smad3-specific signaling in the TGF-ß/Smad-dependent pathway and Wnt/ß-catenin pathway. MAF has an important effect on crosstalk between the TGF-ß/Smad and Wnt/ß-catenin pathway in EMT process by activation of RAS.


Assuntos
Transição Epitelial-Mesenquimal/efeitos dos fármacos , Nefropatias/tratamento farmacológico , Rim/patologia , Proteína Smad3/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Triterpenos/farmacologia , Alisma/química , Angiotensina II/metabolismo , Angiotensina II/farmacologia , Animais , Linhagem Celular , Fibrose/tratamento farmacológico , Rim/efeitos dos fármacos , Rim/metabolismo , Nefropatias/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação/efeitos dos fármacos , Ratos , Fator de Crescimento Transformador beta1/metabolismo , Fator de Crescimento Transformador beta1/farmacologia , Via de Sinalização Wnt/efeitos dos fármacos , Proteínas ras/antagonistas & inibidores
15.
Phytomedicine ; 42: 34-42, 2018 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-29655695

RESUMO

BACKGROUND: Cholestasis is a clinical syndrome of liver damage that is caused by accumulation of bile acids in the liver and systemic circulation. Farnesoid X receptor (FXR) can regulate synthesis, metabolism, and excretion of bile acids. The rhizomes of Alisma orientale is a well-known traditional Chinese medicine to treat edema, obesity, gonorrhea, leukorrhea, diarrhea, hyperlipidemia, and diabetes in China. HYPOTHESIS/PURPOSE: We hypothesized Alisma orientale extract (AOE) to exert hepatoprotective effect against α-naphthylisothiocyanate (ANIT) induced cholestasis in rat. We aimed to investigate the mechanism of AOE. STUDY DESIGN: Male Sprague Dawley rats with intrahepatic cholestasis induced by ANIT were treated with AOE (150, 300, or 600 mg/kg). Rats receiving vehicle (0.5% CMC-Na) served as control. METHODS: 48 h after ANIT administration, rats were sacrificed. Blood was collected to obtain serum and livers were removed for histopathology and protein preparation. Biochemical indicators in serum were determined using commercial kits and triterpenoids were determined by liquid chromatography tandem Qtrap mass spectrometry. Proteomics was analyzed by liquid chromatography tandem ion-trap mass spectrometry. The differently expressed proteins were analyzed via the network database and verified by western blotting. The interaction between triterpenoids and FXR were evaluated by luciferase assay and molecular docking. RESULTS: AOE treatment significantly decreased the serum AST, ALT, TBIL, and intrahepatic TBA and improved the liver pathologic change induced by ANIT. Proteomics analysis indicated that AOE regulated proteins related to bile acid homeostasis via activating farnesoid X receptor (FXR) signaling pathway. Luciferase assay and molecular docking results indicated that triterpenoids could activate FXR, which resulting in ameliorative accumulation of bile acids in the liver by increase of metabolism and transportation for bile acids, and decrease of synthesis for bile acids. CONCLUSION: AOE protected against rat liver injury and cholestasis induced by ANIT by activation of farnesoid X receptor, suggesting that A. orientale could be regarded as a potential hepatoprotective drug.


Assuntos
Alisma/química , Colestase Intra-Hepática/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Receptores Citoplasmáticos e Nucleares/metabolismo , 1-Naftilisotiocianato/toxicidade , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Ácidos e Sais Biliares/metabolismo , Bilirrubina/metabolismo , China , Colestase Intra-Hepática/induzido quimicamente , Colestase Intra-Hepática/patologia , Medicamentos de Ervas Chinesas/química , Homeostase/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Simulação de Acoplamento Molecular , Substâncias Protetoras/farmacologia , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos
16.
J Sep Sci ; 41(4): 839-846, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29178373

RESUMO

The geographic impact on the quality of Alismatis Rhizoma (derived from the tuber of Alisma orientale), a reputable diuretic traditional Chinese medicine, has seldom been evaluated. Here a metabolomics-driven approach targeting the bioactive protostane triterpenes was developed, by incorporating UHPLC with quadrupole time-of-flight mass spectrometry-based untargeted metabolite profiling and multiple reaction monitoring quantitative assay, to probe the triterpene differences between Alismatis Rhizoma samples collected from Sichuan, Fujian, and Jiangxi Provinces. Following the metabolomics workflows, the samples from Sichuan and Jiangxi displayed distinct differences in their triterpene profiles, whereas those from Fujian showed remarkable intra-class variation. Twenty-three triterpenes were identified to contribute most to the differentiated clustering. A sensitive, precise, repeatable, and accurate quantitative assay method was established on a hybrid triple quadrupole-linear ion trap mass spectrometer to quantify the contents of eight triterpene compounds. Taking into account the metabolomics and quantitation results, alisol B 23-acetate and alisol A are significantly different in Alismatis Rhizoma from Sichuan and Jiangxi Provinces, and they may have the potential for geographic discrimination. These results illustrate how geographic difference impacts the triterpene chemistry of Alismatis Rhizoma. Metabolomics-driven chemical comparison is suitable for the quality evaluation of traditional Chinese medicine.


Assuntos
Alisma , Metabolômica , Extratos Vegetais/análise , Triterpenos/análise , Alisma/química , Alisma/metabolismo , Cromatografia Líquida de Alta Pressão , Espectrometria de Massas , Medicina Tradicional Chinesa , Extratos Vegetais/metabolismo , Triterpenos/metabolismo
17.
Nat Prod Res ; 32(2): 189-194, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28649858

RESUMO

Two new protostane-type triterpenoids, 17-epi alisolide (1) and 24-epi alismanol D (2), were isolated from Alisma orientalis together with one known compound. Their structural elucidations were conducted by NMR, UV and HRESIMS spectroscopic analyses, and comparison with the literature data. All the isolated compounds were evaluated for inhibitory effects on HCE-2. Compound 2 displayed moderate inhibitory activity against HCE-2 with IC50 value of 23.1 µM.


Assuntos
Alisma/química , Triterpenos/química , Triterpenos/farmacologia , Carboxilesterase/antagonistas & inibidores , Concentração Inibidora 50 , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Espectrometria de Massas por Ionização por Electrospray , Espectrofotometria Ultravioleta
18.
Nat Prod Res ; 32(23): 2749-2755, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28954548

RESUMO

The chemical constituent investigation of Alisma plantago-aquatica subsp. orientale has led to isolation and identification of thirteen compounds, including one new sesquiterpene, (10S)-11-hydroxy-ß-cyperone (1), three sesquiterpenes (2-4), five phenylpropanoids (5-9), and four alkaloids (10-13). We report herein, for the first time, the presence of compounds 2-13 in the genus Alisma. Their structures were established using 1D and 2D NMR and HRESIMS spectroscopic analyses. All the isolated compounds were assayed for their inhibitory activities against nitric oxide production in LPS-induced RAW 264.7 cells and antioxidant activities by DPPH scavenging assay. Compounds 1-13 displayed significant inhibitory effects against NO production at a certain concentration, while compound 5 showed antioxidant activity with IC50 of 55.28 µM. The interactions of compounds 1, 5, and 11 with iNOS were investigated using molecular docking.


Assuntos
Alisma/química , Anti-Inflamatórios/isolamento & purificação , Antioxidantes/isolamento & purificação , Alcaloides/química , Alcaloides/isolamento & purificação , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Camundongos , Simulação de Acoplamento Molecular , Estrutura Molecular , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/biossíntese , Extratos Vegetais/química , Células RAW 264.7 , Sesquiterpenos/química , Sesquiterpenos/isolamento & purificação
19.
Chem Biodivers ; 14(12)2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29139211

RESUMO

Twenty-eight protostane triterpenoids, including a new degraded one (1), nine new ones (2 - 10), and two new natural ones (11 and 12), have been isolated from the dried rhizomes of Alisma orientale. Alisol R (1) was the first 20,21,22,23,24,25,26,27-octanorprotostane triterpenoid. The absolute configurations of 25-methoxyalisol F (2) and 16ß-hydroperoxyalisol B 23-acetate (3) were determined by X-ray diffraction analysis. In addition, alismaketone-B 23-acetate (28) showed potent vasorelaxant activity on endothelium-intact thoracic aorta rings precontracted with KCl.


Assuntos
Alisma/química , Terpenos/química , 11-beta-Hidroxiesteroide Desidrogenases/antagonistas & inibidores , 11-beta-Hidroxiesteroide Desidrogenases/metabolismo , Alisma/metabolismo , Animais , Aorta/efeitos dos fármacos , Aorta/metabolismo , Humanos , Espectroscopia de Ressonância Magnética , Camundongos , Conformação Molecular , Extratos Vegetais/química , Cloreto de Potássio/toxicidade , Ratos , Rizoma/química , Rizoma/metabolismo , Terpenos/metabolismo , Terpenos/farmacologia , Triterpenos/química , Triterpenos/isolamento & purificação , Triterpenos/farmacologia , Vasodilatadores/química , Vasodilatadores/isolamento & purificação , Vasodilatadores/farmacologia , Difração de Raios X
20.
Molecules ; 22(9)2017 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-28878160

RESUMO

Alismatis rhizoma (AR), the dried rhizoma of Alisma orientale Juzepzuk (Alismataceae), is a traditional Chinese medicine. AR is an important part of many prescriptions and is commonly used as a diuretic agent in Asia. This study aimed to evaluate the diuretic effects of total triterpene extract (TTE) and triterpene component compatibility (TCC, the mixture of alisol B 23-acetate, alisol B, alisol A 24-acetate, alisol A, and alisol C 23-acetate) of AR in saline-loaded rats. The optimal diuretic TCC of AR was optimized using a uniform design. Different doses (5, 20, and 40 mg/kg) of TTE and TCC groups (N1-N8) were orally administered to rats. Urinary excretion rate, pH, and electrolyte excretion were measured in the urine of saline-loaded rats. Results showed that TTE doses increased urine volume and electrolyte excretion compared with the control group. All uniformly designed groups of TCC also increased urine excretion. In addition, optimal diuretic TCC was calculated (alisol B 23-acetate: alisol B: alisol A 24-acetate: alisol A: alisol C 23-acetate 7.2:0.6:2.8:3.0:6.4) and further validated by saline-loaded rats. This study demonstrated that TTE presented a notable diuretic effect by increasing Na⁺, K⁺, and Cl − displacements. The most suitable TTC compatible proportion of alisol B 23-acetate: alisol B: alisol A 24-acetate: alisol A: alisol C 23-acetate for diuretic activity was validated, and triterpenes were the material basis for the diuretic activity of AR.


Assuntos
Alisma/química , Diuréticos/química , Rizoma/química , Triterpenos/química , Animais , Diuréticos/farmacologia , Relação Dose-Resposta a Droga , Íons/química , Masculino , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Ratos , Ratos Sprague-Dawley , Triterpenos/farmacologia
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