RESUMO
Lonicerae japonicae flos and Lonicerae flos are increasingly widely used in food and traditional medicine products around the world. Due to their high demand and similar appearance, they are often used in a confused or adulterated way; therefore, a rapid and comprehensive analytical method is highly required. In this case, the comparative analysis of a total of 100 samples with different species, growth modes, and processing methods was carried out by nuclear magnetic resonance (1H-NMR) spectroscopy and chemical pattern recognition analysis. The obtained 1H-NMR spectrums were employed by principal component analysis (PCA), partial least-squares discriminant analysis (PLS-DA), orthogonal partial least-squares discriminant analysis (OPLS-DA), and linear discriminant analysis (LDA). Specifically, after the dimensionality reduction of data, linear discriminant analysis (LDA) exhibited good classification abilities for the species, growth modes, and processing methods. It is worth noting that the sample prediction accuracy from the testing set and the cross-validation predictions of the LDA models were higher than 95.65% and 98.1%, respectively. In addition, the results showed that macranthoidin A, macranthoidin B, and dipsacoside B could be considered as the main differential components of Lonicerae japonicae flos and Lonicerae Flos, while secoxyloganin, secologanoside, and sweroside could be responsible for distinguishing cultivated and wild Lonicerae japonicae Flos. Accordingly, 1H-NMR spectroscopy combined with chemical pattern recognition gives a comprehensive overview and provides new insight into the quality control and evaluation of Lonicerae japonicae flos.
Assuntos
Medicamentos de Ervas Chinesas , Lonicera , Medicamentos de Ervas Chinesas/química , Cromatografia Líquida de Alta Pressão/métodos , Extratos Vegetais , Lonicera/química , Espectroscopia de Ressonância MagnéticaRESUMO
The fraud phenomenon is currently widespread in the traditional Chinese medicine Radix Astragali (RA) market, especially where high-quality RA is substituted with low-quality RA. In this case, focused on polysaccharides from RA, the classification models were established for discrimination of RA from different growth patterns, origins, species, and growth years. 1H Nuclear Magnetic Resonance (H1-NMR) was used to establish the spectroscopy of polysaccharides from RA, which were used to distinguish RA via chemical pattern recognition methods. Specifically, orthogonal partial least squares discriminant analysis (OPLS-DA) and linear discriminant analysis (LDA) were used to successfully establish the classification models for RA from different growth patterns, origins, species, and growth years. The satisfactory parameters and high accuracy of internal and external verification of each model exhibited the reliable and good prediction ability of the developed models. In addition, the polysaccharide content and immunological activity were also tested, which was evaluated by the phagocytic activity of RAW 264.7. And the result showed that growth patterns and origins significantly affected the quality of RA. However, there was no significant difference in the aspects of origins and growth years. Accordingly, the developed strategy combined with chemical information, biological activity, and multivariate statistical method can provide new insight for the quality evaluation of traditional Chinese medicine.
Assuntos
Medicamentos de Ervas Chinesas , Imageamento por Ressonância Magnética , Polissacarídeos , Espectroscopia de Ressonância MagnéticaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: QiShenYiQi is a Chinese herbal formula composed of Astragalus membranaceus Fisch. ex Bunge, root; Slauia miltiorrhiza Bunge, root and rhizome; Panax notoginseng (Burkill) F.H.Chen, root; and Dalbergia odorifera T.C.Chen, heartwood of trunk and root with a proportion of 10:5:1:0.067. Its dripping pills were approved by the National Medical Products Administration (NMPA) in 2003 and could be used in the clinical treatment of ischemic heart diseases. Ferroptosis is an important pathological mechanism in the process of myocardial ischemia (MI). Whether QSYQ can improve ferroptosis induced by myocardial ischemia is still unclear. AIM OF THE STUDY: In this study, the potential mechanisms of QSYQ against ferroptosis in MI-induced injury were investigated. MATERIALS AND METHODS: The main components of QSYQ were analyzed by HPLC-Q-TOF-MS/MS. MI model was established by ligation of the left anterior descending coronary artery and then treated with QSYQ dropping pills for 14 days. The cardiac function of mice was evaluated by echocardiography. Hematoxylin and eosin (H&E) staining and Masson's trichrome staining were used to detect the pathological changes in heart tissue. Serum biochemical indexes were analyzed by biochemical kit. Transmission electron microscope (TEM) was used to observe the mitochondria ultrastructure and mitochondrial ROS was detected by immunofluorescence. Then, photoacoustic imaging was used to observe the redox status of the mice' hearts. Finally, the mitochondrial dynamics and biogenesis related proteins and the proteins of ferroptosis were analyzed by western blotting. RT-PCR was used to detect the mRNA expression changes of ferroptosis. RESULTS: A total of 20 principal components of QSYQ were characterized by HPLC-Q-TOF-MS/MS. QSYQ significantly improved cardiac function and myocardial injury in MI mice. Furthermore, the lipid peroxidation change levels (MDA, 4-HNE, and GSH) in serum were attenuated and myocardial iron content was reduced after QSYQ treatment. On this basis, QSYQ also improved the expression changes of ferroptosis related mRNA and proteins. In addition, QSYQ promoted mitochondrial biogenesis (PGC-1α, Nrf1, and TFAM) and mitochondrial fusion (MFN-2 and OPA1) and inhibited mitochondrial excessive fission (Phosphorylation of Drp1 at ser616) in vitro and in vivo, indicating that the cardioprotection of QSYQ might be related to promoting mitochondrial biogenesis and dynamic homeostasis. CONCLUSION: In summary, QSYQ could alleviate MI-induced ferroptosis by improving mitochondrial biogenesis and dynamic homeostasis.
Assuntos
Medicamentos de Ervas Chinesas , Ferroptose , Isquemia Miocárdica , Ratos , Camundongos , Animais , Dinâmica Mitocondrial , Espectrometria de Massas em Tandem , Ratos Sprague-Dawley , Medicamentos de Ervas Chinesas/farmacologia , Isquemia Miocárdica/tratamento farmacológico , HomeostaseRESUMO
Lonicerae japonicae flos (LJF, Lonicera japonica Thunb.) is adopted as a core herb for preventing and treating influenza. However, the anti-influenza virus components of LJF and the impact of quality-affecting factors on the anti-influenza activity of LJF have not been systematically investigated. In this study, a strategy integrating anti-influenza virus activity, ultrahigh-performance liquid chromatography fingerprint and chemical pattern recognition was proposed for the efficacy and quality evaluation of LJF. As a result, six bioactive compounds were screened out and identified as neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, 4,5-Di-O-caffeoylquinic acid, sweroside and secoxyloganin. Based on the bioactive compounds, chemical pattern recognition models of LJF were established by a linear discriminant analysis (LDA). The results of the LDA models and anti-influenza virus activity demonstrated that cultivation pattern significantly affected the anti-influenza effect of LJF and that the neuraminidase inhibition rate of wild LJF was significantly higher than that of cultivated LJF. Moreover, the quality of LJF samples with different processing methods and geographical origins showed no obvious difference. Overall, the proposed strategy in the current study revealed the anti-influenza virus components of LJF and provided a feasible method for thequality evaluation of LJF, which has great importance for assuring the clinical effect against influenza of LJF.
Assuntos
Medicamentos de Ervas Chinesas , Lonicera , Ácido Clorogênico/análogos & derivados , Ácido Clorogênico/farmacologia , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Lonicera/química , Neuraminidase , Ácido Quínico/análogos & derivadosRESUMO
Lonicerae japonicae flos (LJF, Lonicera japonica Thunb.) is often confused and/or adulterated with Lonicerae flos (LF, Lonicera macrantha (D.Don) Spreng.). Ecological conditions and processing methods strongly influenced the safety and efficacy of LJF. For the strict quality control of LJF, a rapid and feasible strategy for identification and classification of LJF by species, growth mode, processing method and geographical origin, based on chromatographic profiles and pattern recognition analysis, in 119 batches of Lonicera samples was systematically established. Firstly, comprehensive analysis of the chemical compositions of LJF was achieved using ultra-high performance liquid chromatography (UHPLC). Next, unsupervised principal component analysis showed that the influence of species, growth mode, processing method and geographical origin displayed a decreasing trend. Subsequently, classification models for authentication of LJF samples were established by linear discriminant analysis (LDA) with good classification abilities. Finally, sweroside and secoxyloganin could be considered as markers associated of cultivated and wild LJF, respectively, while 3-O-caffeoylquinic acid and 3,5-Di-O-caffeoylquinic acid could be regarded as markers for LF. Consequently, the findings suggest that UHPLC profiles combined with pattern recognition analysis is precise and feasible strategy for the discrimination and quality control of LJF.
Assuntos
Medicamentos de Ervas Chinesas , Lonicera , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/química , Lonicera/química , Extratos Vegetais/química , Controle de QualidadeRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Rhodiola crenulata (Hook.f. & Thomson) H.Ohba has a long history of clinical application for the prevention and treatment of acute mountain sickness (AMS) in traditional Chinese medicine. However, gaps in knowledge still exist in understanding the underlying mechanisms of Rhodiola crenulata against AMS. AIMS: To address this problem, a comprehensive method was established by combining UHPLC-Q-TOF-MS/MS analysis and network pharmacology. MATERIALS AND METHODS: The ingredients of Rhodiola crenulata were comprehensively analyzed using UHPLC-Q-TOF-MS/MS method. On this basis, a network pharmacology method incorporated target prediction, protein-protein interaction network, gene enrichment analysis and components-targets-pathways network was performed. Finally, the possible mechanisms were verified through molecular docking, in vitro and in vivo experiments. RESULTS: A total of 106 constituents of Rhodiola crenulata were charactered via UHPLC-Q-TOF-MS/MS. The 98 potentially active compounds out of 106 were screened and corresponded to 53 anti-AMS targets. Gene enrichment analysis revealed that hypoxia and inflammation related genes may be the central factors for Rhodiola crenulata to modulate AMS. Molecular docking revealed that TNF, VEGFA and HIF-1α had high affinities to Rhodiola crenulata compounds. Subsequently, Rhodiola crenulata extract was indicated to inhibit the protein expression level of TNF in hypoxia induced H9c2 cells. Lastly, Rhodiola crenulata extract was further verified to ameliorate heart injury and decreased the heart levels of TNF, VEGFA and HIF-1α in acute hypoxia-induced rats. CONCLUSIONS: This study used UHPLC-Q-TOF-MS/MS analysis and a network pharmacology to provide an important reference for revealing the potential mechanism of Rhodiola crenulata in the prevention and treatment of AMS.
Assuntos
Doença da Altitude , Rhodiola , Doença Aguda , Doença da Altitude/tratamento farmacológico , Animais , Cromatografia Líquida de Alta Pressão/métodos , Hipóxia , Simulação de Acoplamento Molecular , Farmacologia em Rede , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Ratos , Rhodiola/química , Espectrometria de Massas em Tandem/métodosRESUMO
Abelmoschus manihot (L.) Medik. (A. manihot) is a traditional Chinese herbal medicine with a variety of pharmacological properties. It was first recorded in Jiayou Materia Medica dating back to the Song dynasty to eliminate urinary tract irritation by clearing away heat and diuretic effect. However, its pharmacological action on urinary tract infections has not been investigated. The present study aims to evaluate the anti-inflammatory activity of A. manihot on a mouse model of lipopolysaccharide (LPS)-induced cystitis. The results showed that A. manihot decreased white blood cell (WBC) count in urine sediments of the cystitis mice, alleviated bladder congestion, edema, as well as histopathological damage, reduced the expression levels of tumor necrosis factor-α, interleukin-6, and interleukin-1ß simultaneously. Moreover, A. manihot administration significantly downregulated the expression levels of TLR4, MYD88, IκBα, p-IκBα, NF-κB p65, and p-NF-κB p65 in LPS-induced cystitis mice. These findings demonstrated the protective effect of A. manihot against LPS-induced cystitis, which is attributed to its anti-inflammatory profile by suppressing TLR4/MYD88/NF-κB pathways. Our results suggest that A. manihot could be a potential candidate for cystitis treatment.
Assuntos
Abelmoschus , Cistite , Abelmoschus/metabolismo , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Feminino , Humanos , Lipopolissacarídeos/farmacologia , Masculino , Camundongos , Fator 88 de Diferenciação Mieloide/metabolismo , Inibidor de NF-kappaB alfa/metabolismo , NF-kappa B/genética , NF-kappa B/metabolismo , Transdução de Sinais , Receptor 4 Toll-Like/metabolismoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Ribes diacanthum Pall (RDP) is mostly distributed in Mongolia. As a Mongolian folk medicinal plant, it is traditionally used to treat kidney diseases by the native inhabitants of Mongolia due to its effect of increasing urine output and eliminating edema. However, its renal protection mechanism remains to be elucidated. AIM OF THE STUDY: To assess the pharmacological mechanism of RDP from an anti-inflammatory point of view using cisplatin (CDDP)-induced kidney injury models in vivo and in vitro. The influence of RDP on the chemotherapy efficacy of CDDP was also evaluated in vitro. MATERIALS AND METHODS: We established a CDDP-induced nephrotoxicity mouse model and a Human Renal Tubular Epithelial (HK-2) damage cellular model, respectively. In vivo, kidney function, the content of urine albumin, and renal histopathology examination were performed to observe the kidney injury. Moreover, the expression and secretion of inflammatory cytokines and adhesive molecules were examined by enzyme-linked immunosorbent assay (ELISA), immunohistochemistry (IHC), and real-time PCR. The key protein levels of mitogen-activated protein kinase/nuclear factor kappa B (MAPK/NF-κB) signaling pathway were measured by western blotting analysis. Electrophoretic mobility shift assay (EMSA) was carried out to detect the activation of NF-κB. In vitro, inflammatory mediators and the proteins related to the NF-κB signaling pathway in HK-2 cells were measured by western blotting analysis. Besides, A549 cell lines were treated with CDDP and RDP to explore RDP's impact on CDDP chemotherapy. RESULTS: Gavage RDP decreased the elevated levels of serum creatinine (Scr), urea nitrogen (BUN), as well as the ratio of urine albumin and creatinine, ameliorated pathological changes of kidney tissue. Correspondingly, the RDP administration group showed a higher survival rate than that of the CDDP exposed group. The expression levels of a plethora of inflammatory mediators were inhibited by RDP treatment compared with the CDDP-exposed group. Furthermore, protein expression levels of MAPK/NF-κB signaling pathway significantly decreased after RDP intervention. For in vitro studies, we confirmed the inhibitory effect of RDP on relative protein expressions involving in the NF-κB pathway. The results also showed that RDP had no impairment on the inhibitory effect of CDDP on A549 cells. CONCLUSION: These findings demonstrated RDP's anti-inflammatory effect against CDDP nephrotoxicity through in vivo and in vitro experiments, and suggested that RDP may have a potential application as an adjuvant medication for CDDP chemotherapy and other inflammatory kidney diseases.
Assuntos
Células Epiteliais/efeitos dos fármacos , Inflamação/prevenção & controle , Nefropatias/induzido quimicamente , Fitoterapia , Ribes/química , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/toxicidade , Linhagem Celular , Cisplatino/administração & dosagem , Cisplatino/toxicidade , Relação Dose-Resposta a Droga , Humanos , Túbulos Renais/citologia , Masculino , Medicina Tradicional da Mongólia , Camundongos , Camundongos Endogâmicos ICR , Plantas Medicinais , Distribuição AleatóriaRESUMO
Rhodiola, especially Rhodiola crenulate and Rhodiola rosea, is an increasingly widely used traditional medicine or dietary supplement in Asian and western countries. Because of the phytochemical diversity and difference of therapeutic efficacy among Rhodiola species, it is crucial to accurately identify them. In this study, a simple and efficient method of the classification of Rhodiola crenulate, Rhodiola rosea, and their confusable species (Rhodiola serrata, Rhodiola yunnanensis, Rhodiola kirilowii and Rhodiola fastigiate) was established by UHPLC fingerprints combined with chemical pattern recognition analysis. The results showed that similarity analysis and principal component analysis (PCA) could not achieve accurate classification among the six Rhodiola species. Linear discriminant analysis (LDA) combined with stepwise feature selection exhibited effective discrimination. Seven characteristic peaks that are responsible for accurate classification were selected, and their distinguishing ability was successfully verified by partial least-squares discriminant analysis (PLS-DA) and orthogonal partial least-squares discriminant analysis (OPLS-DA), respectively. Finally, the components of these seven characteristic peaks were identified as 1-(2-Hydroxy-2-methylbutanoate) ß-D-glucopyranose, 4-O-glucosyl-p-coumaric acid, salidroside, epigallocatechin, 1,2,3,4,6-pentagalloyglucose, epigallocatechin gallate, and (+)-isolarisiresinol-4'-O-ß-D-glucopyranoside or (+)-isolarisiresinol-4-O-ß-D-glucopyranoside, respectively. The results obtained in our study provided useful information for authenticity identification and classification of Rhodiola species.
Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Extratos Vegetais/química , Rhodiola/química , Análise Discriminante , Análise dos Mínimos Quadrados , Análise de Componente Principal , Rhodiola/classificaçãoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: In traditional Chinese medicine (TCM) and modern pharmacodynamics, dried Rehmannia Radix (DRR) possesses prominent anti-thrombotic activity that decreases after processing by nine steaming and drying cycles to develop processed Rehmannia Radix (PRR). Due to the complexity of the DRR components, the chemical mechanism leading to efficacy changes of DRR caused by processing is still unclear. AIM OF STUDY: This study aimed to trace the anti-thrombotic active compounds of DRR and different degrees of processed RR (PRR) and to evaluate the synergistic effects among different active components. MATERIALS AND METHODS: The anti-thrombotic active chemical fraction of DRR extracts was evaluated. Targeted fractions of the processed products of RR were prepared at different processing stages. The changes in monosaccharides, oligosaccharides and secondary metabolites during processing were characterized by multidimensional high-performance liquid chromatography (HPLC). The anti-thrombotic effects of targeted fractions of different RR samples were evaluated by analyzing the length of tail thrombus (LT) and serum biochemical indicators in carrageenan-induced tail-thrombus mice. The spectrum-effect relationships were investigated by partial least squares regression (PLSR) analysis and gray correlation analysis (GRA). Finally, the active compounds were screened by spectrum-effect relationship analysis and validated in vivo, and their synergistic effects were determined by Webb's fraction multiplication method. RESULTS: Six ingredients highly associated with anti-thrombotic activities were screened out by the spectrum-effect relationship analysis, of which oligosaccharides (stachyose, sucrose and raffinose) and iridoid glycosides (catalpol, leonuride and melitoside) possessed a synergistic effect on tumor necrosis factors (TNF-α), interleukin 1ß (IL-1ß) and plasminogen activator inhibitor 1 (PAI-1)/tissue-type plasminogen activator (t-PA) ratio in vivo with synergistic coefficient (SC) > 1. CONCLUSION: The main material basis of the anti-thrombotic activities of DRR is oligosaccharide components of stachyose, raffinose and sucrose, iridoid glycosides components of catalpol, leonuride and melittoside. The two kinds of components exert synergistic anti-thrombotic effects by inhibiting the expression of inflammatory factors and regulating the balance of the fibrinolysis system.
Assuntos
Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Fibrinolíticos/química , Fibrinolíticos/farmacologia , Rehmannia/química , Trombose/tratamento farmacológico , Animais , Cromatografia Líquida de Alta Pressão , Dessecação , Modelos Animais de Doenças , Sinergismo Farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Fibrinolíticos/uso terapêutico , Interleucina-1beta/sangue , Glicosídeos Iridoides/farmacologia , Masculino , Medicina Tradicional Chinesa , Camundongos Endogâmicos ICR , Monossacarídeos/análise , Análise Multivariada , Oligossacarídeos/análise , Oligossacarídeos/farmacologia , Inibidor 1 de Ativador de Plasminogênio/sangue , Análise de Componente Principal , Metabolismo Secundário , Vapor , Trombose/induzido quimicamente , Ativador de Plasminogênio Tecidual/sangue , Fator de Necrose Tumoral alfa/sangueRESUMO
BACKGROUND: Renal fibrosis is a common pathological outcome of chronic kidney diseases (CKD) that is considered as a global public health issue with high morbidity and mortality. The dry corolla of Abelmoschus manihot (L.) Medik. (AMC) has been used for chronic nephritis in clinic and showed a superior effect in alleviating proteinuria in CKD patients to losartan. However, the effective components and underlying mechanism of AMC in the treatment of renal fibrosis have not been systematically clarified. METHODS: Based on drug-likeness evaluation, oral bioavailability prediction and compound contents, a systematic network pharmacology analysis was conducted to predict the active ingredients. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes pathway analysis and protein-protein interaction analysis were applied to predict the potential pathway and target of AMC against renal fibrosis. The formula of component contribution index (CI) based on the algorithm was used to screen the principal active compounds of AMC in the treatment of renal fibrosis. Finally, pharmacological evaluation was conducted to validate the protective effect and primary predicted mechanism of AMC in the treatment of renal fibrosis on a 5/6 nephrectomy mice model. RESULTS: Fourteen potential active components of AMC possessing favorable pharmacokinetic profiles and biological activities were selected and hit by 17 targets closely related to renal fibrosis. Quercetin, caffeic acid, 9.12-octadecadienoic acid, and myricetin are recognized as the more highly predictive components as their cumulative contribution rate reached 85.86%. The AMC administration on 5/6 nephrectomy mice showed a protective effect on kidney function and renal fibrosis. The hub genes analysis revealed that AMC plays a major role in inhibiting epithelial-to-mesenchymal transition during renal fibrosis. CONCLUSION: Our results predicted active components and potential targets of AMC for the application to renal fibrosis from a holistic perspective, as well as provided valuable direction for further research of AMC and improved comprehension of renal fibrosis pathogenesis.
Assuntos
Abelmoschus/química , Medicamentos de Ervas Chinesas/farmacologia , Fibrose/tratamento farmacológico , Extratos Vegetais/farmacologia , Substâncias Protetoras/farmacologia , Insuficiência Renal Crônica/tratamento farmacológico , Animais , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/isolamento & purificação , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Fibrose/metabolismo , Fibrose/patologia , Camundongos , Camundongos Endogâmicos ICR , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Substâncias Protetoras/química , Substâncias Protetoras/isolamento & purificação , Insuficiência Renal Crônica/metabolismo , Insuficiência Renal Crônica/patologiaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Ribes diacanthum Pall (RDP), a folk medicine, has been widely used in Mongolia to treat urinary system diseases. AIM OF THE STUDY: To investigate the effectiveness of RDP on unilateral ureteral obstruction (UUO)-induced renal interstitial fibrosis and the underlying mechanisms. MATERIALS AND METHODS: A total of 60 mice were randomly divided into six groups: sham group, sham plus RDP (40â¯mg/kg) group, UUO model group, and UUO model plus RDP (10, 20 or 40â¯mg/kg) groups. After surgery, aqueous extract of RDP were administrated intragastrically (i.g) daily for a week and ipsilateral kidneys were collected seven days after surgery. Levels of blood urea nitrogen (BUN) and serum creatinine (Scr) were detected to reflect the kidney injury. Hematoxylin & eosin and Masson's trichrome staining were used to evaluate the kidney morphological changes and fibrosis, respectively. ELISA was used to examine the levels of pro-inflammatory cytokines. Immunohistochemistry, western blot and PCR were used to examine the expression levels of key proteins involved in transforming growth factor (TGF-ß)/Smad and mitogen-activated protein kinase (MAPK) signaling pathways. RESULTS: RDP treatment attenuates the level of BUN and kidney fibrosis in UUO mice, decreases the expressions of interleukin-6, tumor necrosis factor-α, Interleukin-1α, TGF-ß1, monocyte chemotactic protein-1, α-smooth muscle actin, collagen I, fibronectin, and vimentin, while increases the expressions of E-cadherin and hepatocyte growth factor. Moreover, RDP administration significantly decreases the levels of p-Smad2/3, p-ERK1/2, p-p38 and p-JNK, while increases the expression level of Smad7 in UUO models. CONCLUSION: These data demonstrate that RDP ameliorates renal fibrosis through TGF-ß/Smad and MAPK pathways in a UUO mouse model.
Assuntos
Citocinas/metabolismo , Nefropatias/metabolismo , Extratos Vegetais/farmacologia , Ribes , Obstrução Ureteral/metabolismo , Animais , Linhagem Celular , Citocinas/genética , Fibrose , Rim/patologia , Nefropatias/tratamento farmacológico , Nefropatias/etiologia , Masculino , Camundongos Endogâmicos ICR , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Fitoterapia , Componentes Aéreos da Planta , Extratos Vegetais/uso terapêutico , Ratos , Transdução de Sinais/efeitos dos fármacos , Obstrução Ureteral/complicações , Obstrução Ureteral/tratamento farmacológicoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: In traditional Chinese medicine (TCM), Rehmanniae Radix (RR, derived from the root of Rehmannia glutinosa (Gaertn.) DC.) is commonly used as natural medicine for thousands of years, two types including the dried and rice-wine processed RR were used for different clinical purposes respectively, which were the typical case that pharmaceutical effect changed by processing in TCM. AIM OF STUDY: The goal of this study was to investigate the differences in the antithrombosis and hematopoietic effects of extracts of dried and processed RR (DRR and PRR) in vivo, and to explore the chemical basis underlying changes of medicinal properties caused by processing. MATERIALS AND METHODS: The aqueous extracts of DRR and PRR were prepared. Protective effect of varying doses of different extracts were investigated in type-I carrageenan induced mice tail thrombosis and cyclophosphamide induced myelosuppression model. The chemical composition of DRR and PRR extracts were determined by High Performance Liquid Chromatography coupled with tandem quadrupole time-of-flight Mass Spectrometry (HPLC/Q-TOF-MS). RESULTS: In antithrombosis activity tests, PRR possessed less ameliorated effects than DRR in the model mouse on body temperature, tail thrombus length and blood flow. Both DRR and PRR had no significant influence on prothrombin time (PT) and activated partial thromboplastin time (APTT), only high dose DRR could decrease the content of fibrinogen (FIB) in plasma. Histological examination of lung tissue suggested that thrombosis was significantly improved in DRR-H group. For myelosuppression model, only PRR could improve peripheral hemogram, both DRR and PRR had hematopoietic effects as demonstrated by their abilities to ameliorate the bone marrow nucleated cells (BMNC) and pathology of bone marrow tissue. The hematopoietic effects of PRR were significantly more potent than that of DRR at the concentration of 9â¯g/kg. By comparing the chemical composition, we found that iridoid glycosides were decreased and furfural derivatives increased in DRR after processing which may be the chemical mechanism contribute to the differences in efficacy. CONCLUSIONS: According to the results of this research, processing with rice wine for nine cycles significantly reduced antithrombotic effects and enhanced the hematopoietic effects of DRR as demonstrated in model mice. It can scientifically explain the different effect among two types of RR in clinical through the diverse method of processing and usage. Meanwhile, the predicted activity compounds from two types of RR can be potential candidates for the treatment of thrombosis and anemia.
Assuntos
Fibrinolíticos/farmacologia , Hematínicos/farmacologia , Extratos Vegetais/farmacologia , Rehmannia , Animais , Dessecação , Fibrinolíticos/química , Hematínicos/química , Hematopoese/efeitos dos fármacos , Masculino , Camundongos Endogâmicos ICR , Oryza , Extratos Vegetais/química , Raízes de Plantas/química , Rehmannia/química , Trombose/tratamento farmacológico , VinhoRESUMO
BACKGROUND: Hawthorn (Crataegus pinnatifida) is a Chinese medicinal plant traditionally used in the treatment of hyperlipidemia. Recently, studies indicated free radical scavenging was one of the major pathways to alleviate hyperlipidemia. Moreover, hawthorn fruit is a rich source of phenols, which quench free radical and attenuate hyperlipidemia. However, the phenols vary with processing methods, especially solvent type. OBJECTIVE: Our aim was to compare hypolipidemic and antioxidant effects of aqueous and ethanol extracts of hawthorn fruit in hyperlipidemia rats. MATERIALS AND METHODS: After a 4-week treatment of high-fat emulsion, lipid profile levels and antioxidant levels of two extracts were determined using commercial analysis. Total phenols content in the extract of hawthorn fruit was determined colorimetrically by the Folin-Ciocalteu method. RESULTS: Both ethanol and aqueous extracts of hawthorn fruit possessed hypolipidemic and antioxidant activities. Simultaneously, stronger activities were observed in ethanol extract. Besides, total phenols content in ethanol extract from the same quality of hawthorn fruit was 3.9 times more than that in aqueous extract. CONCLUSION: The obvious difference of hypolipidemic and antioxidant effects between ethanol extract and aqueous extract of hawthorn fruit was probably due to the presence of total phenols content, under the influence of extraction solvent. SUMMARY: Ethanol extract of hawthorn fruit exhibited more favorable hypolipidemic and antioxidant effects than aqueous extract. The higher effects could be due to the higher content of total phenols that varies with extraction solvent. Abbreviations used: TC: Total cholesterol, TG: Triglyceride, LDL-C: Low-density lipoprotein cholesterol, HDL-C: High-density lipoprotein cholesterol, GSH-Px: Glutathione peroxidase, SOD: Superoxide dismutase, MDA: Malondialdehyde, CAT: Catalase, NO: Nitric oxide, NOS: Nitric oxide synthase, SR-BI: Scavenger receptor Class B Type I.