RESUMEN
Mahonia bealei and Mahonia fortunei are important plant resources in Traditional Chinese Medicine that are valued for their high levels of benzylisoquinoline alkaloids (BIAs). Although the phytotoxic activity of BIAs has been recognized, information is limited on the mechanism of action by which these compounds regulate photosynthetic activity. Here, we performed comparative chloroplast genome analysis to examine insertions and deletions in the two species. We found a GATA-motif located in the promoter region of the ndhF gene of only M. bealei. K-mer frequency-based diversity analysis illustrated the close correlation between the GATA-motif and leaf phenotype. We found that the GATA-motif significantly inhibits GUS gene expression in tobacco during the dark-light transition (DLT). The expression of ndhF was downregulated in M. bealei and upregulated in M. fortunei during the DLT. NDH-F activity was remarkably decreased and exhibited a significant negative correlation with BIA levels in M. bealei during the DLT. Furthermore, the NADPH produced through photosynthetic metabolism was found to decrease in M. bealei during the DLT. Taken together, our results indicate that this GATA-motif might act as the functional site by which BIAs inhibit photosynthetic metabolism through downregulating ndhF expression during the DLT.
Asunto(s)
Alcaloides , Bencilisoquinolinas , Mahonia , Mahonia/química , Extractos Vegetales/farmacología , CloroplastosRESUMEN
Purpose: This study aims to investigate the potential of Oregon grape root extracts to modulate the activity of P-glycoprotein. Methods: We performed 3H-CsA or 3H-digoxin transport experiments in the absence or presence of two sources of Oregon grape root extracts (E1 and E2), berberine or berbamine in Caco-2 and MDCKII-MDR1 cells. In addition, real time quantitative polymerase chain reaction (RT-PCR) was performed in Caco-2 and LS-180 cells to investigate the mechanism of modulating P-glycoprotein. Results: Our results showed that in Caco-2 cells, Oregon grape root extracts (E1 and E2) (0.1-1 mg/mL) inhibited the efflux of CsA and digoxin in a dose-dependent manner. However, 0.05 mg/mL E1 significantly increased the absorption of digoxin. Ten µM berberine and 30 µM berbamine significantly reduced the efflux of CsA, while no measurable effect of berberine was observed with digoxin. In the MDCKII-MDR1 cells, 10 µM berberine and 30 µM berbamine inhibited the efflux of CsA and digoxin. Lastly, in real time RT-PCR study, Oregon grape root extract (0.1 mg/mL) up-regulated mRNA levels of human MDR1 in Caco-2 and LS-180 cells at 24 h. Conclusion: Our study showed that Oregon grape root extracts modulated P-glycoprotein, thereby may affect the bioavailability of drugs that are substrates of P-glycoprotein.
Asunto(s)
Miembro 1 de la Subfamilia B de Casetes de Unión a ATP , Berberina , Mahonia , Extractos Vegetales , Humanos , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Berberina/farmacología , Transporte Biológico/efectos de los fármacos , Células CACO-2 , Digoxina/metabolismo , Mahonia/química , Extractos Vegetales/química , Extractos Vegetales/farmacología , Raíces de Plantas/química , Animales , Perros , Ciclosporina/metabolismo , Células de Riñón Canino Madin DarbyRESUMEN
Depression has become an important disease threatening human health. In recent years, the efficacy of Traditional Chinese Medicine (TCM) in treating the disease has become increasingly prominent, so it is meaningful to find new antidepressant TCM. Mahonia fortune (Lindl.) Fedde is a primary drug in traditional formulas for the treatment of depression, and alkaloids are the main components of it. However, the detailed mechanism of Mahonia alkaloids (MA) on depression remains unclear. This study aimed to investigate the effect of MA on gap junction function in depression via the miR-205/Cx43 axis. The antidepressant effects of MA were observed by a rat model of reserpine-induced depression and a model of corticosterone (CORT)-induced astrocytes. The concentrations of neurotransmitters were measured by ELISA, the expression of Connexin 43 (Cx43) protein was measured by Immunohistochemistry and western-blot, brain derived neurotrophic factor (BDNF), cAMP-response element binding protein (CREB) proteins were measured by western-blot, the pathological changes of prefrontal cortex were observed by hematoxylin-eosin (H&E) staining. Luciferase reporter assay was performed to verify the binding of miR-205 and Cx43. The regulation effect of Cx43 on CREB was verified by interference experiment. Gap junction dysfunction was detected by fluorescent yellow staining. The results confirmed that MA remarkably decreased miR-205 expression and increased Cx43, BDNF, CREB expression in depression rat and CORT-induced astrocytes. In addition, after overexpression of miR-205 in vitro, the decreased expression of Cx43, BDNF and CREB could be reversed by MA. Moreover, after interfering with Cx43, the decreased expression of CREB and BDNF could be reversed by MA. Thus, MA may ameliorate depressive behavior through CREB/BDNF pathway regulated by miR-205/Cx43 axis.
Asunto(s)
Alcaloides , Conexina 43 , Uniones Comunicantes , Mahonia , MicroARNs , Animales , Ratas , Antidepresivos/farmacología , Antidepresivos/uso terapéutico , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Conexina 43/metabolismo , Corticosterona , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Depresión/inducido químicamente , Depresión/tratamiento farmacológico , Depresión/metabolismo , Uniones Comunicantes/metabolismo , Uniones Comunicantes/patología , Hipocampo/metabolismo , Mahonia/química , MicroARNs/metabolismo , Reserpina , Alcaloides/farmacología , Alcaloides/uso terapéuticoRESUMEN
Mahonia bealei is one of the important members of the genus Mahonia and Traditional Chinese Medicine (TCM). Several compounds isolated from this plant have exhibited useful biological activities. Polysaccharides, an important biomacromolecule have been underexplored in case of M. bealei. In this study, hot water extraction and ethanol precipitation were used for the extraction of polysaccharides from the stem of M. bealei, and then extract was purified using ultrafiltration membrane at 50,000 Da cut off value. Characterization of the purified M. bealei polysaccharide (MBP) was performed using Fourier Transform Infrared Spectroscopy (FT-IR), along with Scanning Electron Microscopy (SEM), X-ray crystallography XRD analysis and Thermal gravimetric analysis (TGA). The purified polysaccharide MBP was tested for antioxidant potential by determining its reducing power, besides determining the DPPH, ABTS, superoxide radical, and hydroxyl radical scavenging along with ferrous ion chelating activities. An increased antioxidant activity of the polysaccharide was reported with increase in concentration (0.5 to 5 mg/ml) for all the parameters. Antimicrobial potential was determined against gram positive and gram-negative bacteria. 20 µg/ml MBP was found appropriate with 12 h incubation period against Escherichia coli and Bacillus subtilis bacteria. We conclude that polysaccharides from M. bealei possess potential ability of biological importance; however, more studies are required for elucidation of their structure and useful activities.
Asunto(s)
Berberis , Mahonia , Antioxidantes/química , Depuradores de Radicales Libres , Mahonia/química , Polisacáridos/farmacología , Espectroscopía Infrarroja por Transformada de Fourier , AguaRESUMEN
Lead compound is an important concept for modern drug discovery. In this study, a new concept of lead chemome and an efficient strategy to discover lead chemome were proposed. Compared with the concept of lead compound, lead chemome can provide not only the starting point for drug development, but also the direction for structure optimization. Two traditional Chinese medicines of Mahonia bealei and Mahonia fortunei were used as examples to illustrate the strategy. Based on natural chromatogram-effect correlation (NCEC), berberine, palmatine and jatrorrhizine were discovered as acetylcholinesterase (AchE) inhibitors. Taking the three compounds as template molecules, a lead chemome consisting of 10 structurally related natural compounds were generated through natural structure-effect correlation (NSEC). In the lead chemome, the IC50 values of jatrorrhizine, berberine, coptisine, palmatine and epiberberine are at nanomolar level, which are comparable to a widely used drug of galantamine. Pharmacophore modeling shows that the positive ionizable group and aromatic rings are important substructures for AchE inhibition. Molecular docking further shows that pi-cation interaction and pi-pi stacking are critical for compounds to maintain nanomolar IC50 values. The structure-activity information is helpful for drug design and structure optimization. This work also expanded the traditional understanding of "stem is the medicinal part of Mahonia bealei and Mahonia fortunei". Actually, all parts except the leaf of Mahonia bealei exhibited potent AchE-inhibitory activity. This study provides not only a strategy to discover lead chemome for modern drug development, but also a reference for the application of different parts of medicinal plants.
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Medicamentos Herbarios Chinos/química , Plomo , Mahonia/química , Plomo/análisis , Plomo/química , Simulación del Acoplamiento Molecular , Fitoquímicos/análisis , Fitoquímicos/química , Hojas de la Planta/químicaRESUMEN
In this study, a rapid and highly efficient method was developed for the separation of eight isoquinoline alkaloids using supercritical fluid chromatography. The separation conditions were carefully optimized including stationary phases, additives, backpressure, and temperature. Compared to high-performance liquid chromatography, the use of supercritical fluid chromatography could provide a 13 times faster separation. Subsequently, the method was validated and applied for the determination of eight alkaloids from different parts of Mahonia bealei (Fort.) Carr. (stem, root, leaf, and seed). The results indicated a good repeatability with relative standard deviations for overall precisions lower than 3.2%. The limit of detection was between 0.4 and 2.3 µg/mL while limit of quantitation ranged from 1.5 to 7.5 µg/mL. Recovery ranged from 95.7 to 102.5% indicating a validity of recovery. The content of total eight alkaloids was the highest in stem (66.0 µg/g) and root (65.1 µg/g) compared to leaf or seed. Moreover, anti-acetylcholinesterase activity for those extracts was evaluated by Ellman's colorimetric assay. As a result, the acetylcholinesterase inhibitory activity of the extracted samples was in the following decreasing order: stem > root > leaf or seed. In conclusion, the results indicated that supercritical fluid chromatography could be a useful tool for quality control of Mahonia bealei (Fort.) Carr. containing alkaloids as active compounds.
Asunto(s)
Alcaloides/aislamiento & purificación , Isoquinolinas/aislamiento & purificación , Mahonia/química , Alcaloides/química , Cromatografía con Fluido Supercrítico , Isoquinolinas/química , Estructura Molecular , Hojas de la Planta/química , Raíces de Plantas/química , Tallos de la Planta/química , Plantas Medicinales/química , Semillas/químicaRESUMEN
Melanoma is a serious form of skin cancer that begins in cells known as melanocytes. While it is less common than the other forms of skin cancer, melanoma is more dangerous because of its ability to spread to other organs more rapidly if it is not treated at an early stage. The number of people diagnosed with melanoma has increased over the last few decades. The most widely used treatments include surgery, chemotherapy, and radiation therapy. The search for new drugs to treat various cancers is one of the most important challenges of modern scientific research. Some isoquinoline alkaloids found in different plant species have strong cytotoxic effects on various cancer cells. We tested the effect of isoquinoline alkaloids and extracts obtained from various parts of Mahonia aquifolium collected in various vegetation seasons on human melanoma cancer cells and our data indicated that investigated extract induced significant reduction in cell viability of Human malignant melanoma cells (A375), human Caucasian malignant melanoma cell line (G361), and human malignant melanoma cell line (SKMEL3 cancer cell lines in a dose- and time-dependent manner. Differences in cytotoxic activity were observed for extracts obtained from various parts of Mahonia aquifolium. Significant differences were also obtained in the alkaloids content and cytotoxic activity of the extracts depending on the season of collection of plant material. Our investigations exhibit that these plant extracts can be recommended for further in vivo experiments in order to confirm the possibility of their use in the treatment of human melanomas.
Asunto(s)
Alcaloides/química , Antineoplásicos/química , Antineoplásicos/farmacología , Isoquinolinas/química , Isoquinolinas/farmacología , Mahonia/química , Estaciones del Año , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Humanos , Mahonia/crecimiento & desarrollo , Corteza de la Planta/químicaRESUMEN
Mahonia aquifolium and its secondary metabolites have been shown to have anticancer potential. We performed MTT, scratch, and colony formation assays; analyzed cell cycle phase distribution and doxorubicin uptake and retention with flow cytometry; and detected alterations in the expression of genes involved in the formation of cell-cell interactions and migration using quantitative real-time PCR following treatment of lung adenocarcinoma cells with doxorubicin, M. aquifolium extracts, or their combination. MTT assay results suggested strong synergistic effects of the combined treatments, and their application led to an increase in cell numbers in the subG1 phase of the cell cycle. Both extracts were shown to prolong doxorubicin retention time in cancer cells, while the application of doxorubicin/extract combination led to a decrease in MMP9 expression. Furthermore, cells treated with doxorubicin/extract combinations were shown to have lower migratory and colony formation potentials than untreated cells or cells treated with doxorubicin alone. The obtained results suggest that nontoxic M. aquifolium extracts can enhance the activity of doxorubicin, thus potentially allowing the application of lower doxorubicin doses in vivo, which may decrease its toxic effects in normal tissues.
Asunto(s)
Adenocarcinoma del Pulmón/patología , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Doxorrubicina/administración & dosificación , Neoplasias Pulmonares/patología , Mahonia/química , Extractos Vegetales/farmacología , Células A549 , Adenocarcinoma del Pulmón/tratamiento farmacológico , Berberina/farmacología , Ciclo Celular , Movimiento Celular , Proteínas de Unión al ADN/metabolismo , Sinergismo Farmacológico , Endonucleasas/metabolismo , Prueba de Complementación Genética , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Ocludina/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , beta Catenina/metabolismoRESUMEN
A simple and efficient high-performance liquid chromatography method combined with chemical pattern recognition was established for quality evaluation of Mahonia bealei (Fort.) Carr. A common pattern of 30 characteristic peaks was applied for similarity analysis, hierarchical cluster analysis, principal component analysis, and partial least squares discriminant analysis in the 37 batches of M. bealei (Fort.) Carr. to discriminate wild M. bealei (Fort.) Carr., cultivated M. bealei (Fort.) Carr., and its substitutes. The results showed that partial least squares discriminant analysis was the most effective method for discrimination. Eight characteristics peaks with higher variable importance in projection values were selected for pattern recognition model. A permutation test and 26 batches of testing set samples were performed to validate the model that was successfully established. All of the training and testing set samples were correctly classified into three clusters (wild M. bealei (Fort.) Carr., cultivated M. bealei (Fort.) Carr., and its substitutes) based on the selected chemical markers. Moreover, 26 batches of unknown samples were used to predict the accuracy of the established model with a discrimination accuracy of 100%. The obtained results indicated that the method showed great potential application for accurate evaluation and prediction of the quality of M. bealei (Fort.) Carr.
Asunto(s)
Medicamentos Herbarios Chinos/análisis , Mahonia/química , Extractos Vegetales/análisis , Cromatografía Líquida de Alta Presión , Análisis Discriminante , Análisis de Componente PrincipalRESUMEN
The stems of Mahonia fortunei (MF) are commonly used in Chinese Traditional Medicine and contain multiple bioactive compounds, including 3,4,5-trimethoxyphenol-1-O-ß-d-glucopyranoside (1), 5-hydroxypicolinic acid methyl ester (2), acortatarin A (3), syringic acid (4), 9-epi-acortatarin A (5), vomifoliol (6), corydaldine (7), noroxyhydrastinine (8), columbamine (9), jatrorrhizine (10), palmatine (11), berberine (12) and schisandrin (13). The pharmacokinetics of these 13 compounds in the rat plasma were assessed using a novel sensitive, rapid, and specific UPLC-ESI-MS/MS method after oral administration of an aqueous extract of MF stems. Carbamazepine was employed as the internal standard (IS) and all samples were precipitated with acetonitrile. Chromatographic separation was performed on a C18 column using a gradient elution at 0.3â¯mL/min, with the mobile phase consisting of acetonitrile and 0.06 % formic acid and 5â¯mM ammonium acetate aqueous solution. The calibration curves showed satisfactory linearity in the examination area (r2â¯≥â¯0.99). The accuracy, precision, extraction recovery, matrix effect, and stability were within acceptable ranges. The method successfully assessed the pharmacokinetics of these 13 compounds. In vitro, compound 12 exhibited potent inhibitory activity against production of nitric oxide (NO) in the RAW264.7 cell line when stimulated by lipopolysaccharide (LPS), while compounds 7, 12, and 13 were the most potent inhibitors of NO production in the BV2 cell line when stimulated by LPS. The IC50 values of compounds 7, 12 and 13 were 42.81, 20.55 and 22.74⯵M. We conclude that these compounds have promise for clinical application, although their synergistic action may be more effective than that by any single compound alone.
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Antiinflamatorios/análisis , Mahonia/química , Extractos Vegetales/análisis , Administración Oral , Animales , Antiinflamatorios/farmacocinética , Antiinflamatorios/farmacología , Cromatografía Líquida de Alta Presión/métodos , Concentración 50 Inhibidora , Masculino , Ratones , Óxido Nítrico/metabolismo , Extractos Vegetales/farmacocinética , Extractos Vegetales/farmacología , Células RAW 264.7 , Ratas , Ratas Sprague-Dawley , Espectrometría de Masa por Ionización de Electrospray/métodos , Espectrometría de Masas en Tándem/métodosRESUMEN
Mahonia bealei (Fort.) Carr. (M. bealei) plays an important role in the treatment of many diseases. In the present study, a comprehensive method combining supercritical fluid chromatography (SFC) fingerprints and chemical pattern recognition (CPR) for quality evaluation of M. bealei was developed. Similarity analysis, hierarchical cluster analysis (HCA), principal component analysis (PCA) were applied to classify and evaluate the samples of wild M. bealei, cultivated M. bealei and its substitutes according to the peak area of 11 components but an accurate classification could not be achieved. PLS-DA was then adopted to select the characteristic variables based on variable importance in projection (VIP) values that responsible for accurate classification. Six characteristics peaks with higher VIP values (≥1) were selected for building the CPR model. Based on the six variables, three types of samples were accurately classified into three related clusters. The model was further validated by a testing set samples and predication set samples. The results indicated the model was successfully established and predictive ability was also verified satisfactory. The established model demonstrated that the developed SFC coupled with PLS-DA method showed a great potential application for quality assessment of M. bealei.
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Berberis/química , Mahonia/química , Extractos Vegetales/química , Cromatografía Líquida de Alta Presión , Cromatografía con Fluido Supercrítico , Hojas de la Planta/química , Análisis de Componente PrincipalRESUMEN
An increase in adipose tissue is caused by the increased size and number of adipocytes. Lipids accumulate in intracellular stores, known as lipid droplets (LDs). Recent studies suggest that parameters such as LD size, shape and dynamics are closely related to the development of obesity. Berberine (BBR), a natural plant alkaloid, has been demonstrated to possess anti-obesity effects. However, it remains unknown which cellular processes are affected by this compound or how effective herbal extracts containing BBR and other alkaloids actually are. For this study, we used extracts of Coptis chinensis, Mahonia aquifolium, Berberis vulgaris and Chelidonium majus containing BBR and other alkaloids and studied various processes related to adipocyte functionality. The presence of extracts resulted in reduced adipocyte differentiation, as well as neutral lipid content and rate of lipolysis. We observed that the intracellular fatty acid exchange was reduced in different LD size fractions upon treatment with BBR and Coptis chinensis. In addition, LD motility was decreased upon incubation with BBR, Coptis chinensis and Chelidonium majus extracts. Furthermore, Chelidonium majus was identified as a potent fatty acid uptake inhibitor. This is the first study that demonstrates the selected regulatory effects of herbal extracts on adipocyte function.
Asunto(s)
Adipocitos/efectos de los fármacos , Ácidos Grasos/metabolismo , Hipolipemiantes/farmacología , Gotas Lipídicas/efectos de los fármacos , Lipólisis/efectos de los fármacos , Extractos Vegetales/farmacología , Adipocitos/química , Berberina/farmacología , Berberis/química , Diferenciación Celular/efectos de los fármacos , Línea Celular , Chelidonium/química , Cromatografía de Gases , Cromatografía Líquida de Alta Presión , Coptis/química , Cromatografía de Gases y Espectrometría de Masas , Humanos , Lípidos/análisis , Mahonia/químicaRESUMEN
Mahonia bealei (Fort.) Carr. is an economically important plant that is widely cultivated in Southwest China. Its leaves are commonly used for tea and contain an abundance of antioxidant compounds. However, methods of the systematic purification of antioxidants from M. bealei are lacking. In this study, antioxidants from this plant were effectively and rapidly enriched. First, antioxidants were screened using online 1,1-diphenyl-2-picryl-hydrazyl radical (DPPH)-high performance liquid chromatography (HPLC), followed by separation using high-speed countercurrent chromatography with an optical solvent system composed of n-hexane/ethyl acetate/methanol/water (1:5:1:5, v/v/v/v). Three phenolics-chlorogenic acid (1, 8.3 mg), quercetin-3-O-ß-d-glucopyranoside (2, 20.5 mg), and isorhamnetin-3-O-ß-d-glucopyranoside (3, 28.4 mg)-were obtained from the ethyl acetate-soluble fraction (240 mg) by one-step separation. The chemical structures of the phenolics were characterized by MS and NMR techniques, and the purity of each compound was >92.0% as determined by HPLC. The isolated compounds were assessed by scavenging activities on DPPH and superoxide radicals as well as cytoprotective assays, all of which showed similar trends regarding the antioxidant capacities of the compounds. Moreover, compounds 1-3 significantly attenuated the lipid peroxidation and antioxidant enzyme activities in H2O2-treated RAW264.7 cells. Our study demonstrated the efficiency of a newly developed integrative system for the comprehensive characterization of pure compounds from M. bealei, which will allow their use as reference substances.
Asunto(s)
Antioxidantes/aislamiento & purificación , Peroxidación de Lípido/efectos de los fármacos , Mahonia/química , Fenoles/aislamiento & purificación , Animales , Antioxidantes/química , Antioxidantes/farmacología , Cromatografía Líquida de Alta Presión , Peróxido de Hidrógeno/efectos adversos , Ratones , Estructura Molecular , Estrés Oxidativo/efectos de los fármacos , Fenoles/química , Fenoles/farmacología , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/farmacología , Hojas de la Planta/química , Células RAW 264.7RESUMEN
The prodrug potential of Mahonia aquifolium, a plant used for centuries in traditional medicine, recently gained visibility in the literature, and the activity of several active compounds isolated from its extracts was studied on biologic systems in vitro and in vivo. Whereas the antioxidative and antitumor activities of M. aquifolium-derived compounds were studied at some extent, there are very few data about their outcome on the immune system and tumor cells. To elucidate the M. aquifolium potential immunomodulatory and antiproliferative effects, the bark, leaf, flower, green fruit, and ripe fruit extracts from the plant were tested on peripheral blood mononuclear cells and tumor cells. The extracts exert fine-tuned control on the immune response, by modulating the CD25 lymphocyte activation pathway, the interleukin-10 signaling, and the tumor necrosis-alpha secretion in four distinct human peripheral blood mononuclear cell (PBMC) subpopulations. M. aquifolium extracts exhibit a moderate cytotoxicity and changes in the signaling pathways linked to cell adhesion, proliferation, migration, and apoptosis of the tumor cells. These results open perspectives to further investigation of the M. aquifolium extract prodrug potential.
Asunto(s)
Factores Inmunológicos/farmacología , Inmunomodulación/efectos de los fármacos , Leucocitos Mononucleares/efectos de los fármacos , Activación de Linfocitos/inmunología , Mahonia/química , Neoplasias/tratamiento farmacológico , Extractos Vegetales/farmacología , Adulto , Apoptosis , Movimiento Celular , Proliferación Celular , Células Cultivadas , Humanos , Subunidad alfa del Receptor de Interleucina-2/metabolismo , Leucocitos Mononucleares/inmunología , Leucocitos Mononucleares/metabolismo , Leucocitos Mononucleares/patología , Activación de Linfocitos/efectos de los fármacos , Masculino , Neoplasias/inmunología , Neoplasias/metabolismo , Neoplasias/patologíaRESUMEN
Oxidative stress and inflammation are interlinked processes. The aim of the study was to perform a phytochemical analysis and to evaluate the antioxidant and anti-inflammatory activities of ethanolic Mahonia aquifolium flower (MF), green fruit (MGF), and ripe fruit (MRF) extracts. Plant extract chemical composition was evaluated by HLPC. A DPPH test was used for the in vitro antioxidant activity. The in vivo antioxidant effects and the anti-inflammatory potential were tested on a rat turpentine oil-induced inflammation, by measuring serum nitric oxide (NOx) and TNF-alpha, total oxidative status (TOS), total antioxidant reactivity (TAR), oxidative stress index (OSI), 3-nitrothyrosine (3NT), malondialdehyde (MDA), and total thiols (SH). Extracts were administrated orally in three dilutions (100%, 50%, and 25%) for seven days prior to inflammation. The effects were compared to diclofenac. The HPLC polyphenol and alkaloid analysis revealed chlorogenic acid as the most abundant compound. All extracts had a good in vitro antioxidant activity, decreased NOx, TOS, and 3NT, and increased SH. TNF-alpha was reduced, and TAR increased only by MF and MGF. MDA was not influenced. Our findings suggest that M. aquifolium has anti-inflammatory and antioxidant effects that support the use in primary prevention of the inflammatory processes.
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Antiinflamatorios/química , Antioxidantes/química , Flores/química , Frutas/química , Mahonia/química , Extractos Vegetales/química , Animales , Antiinflamatorios/farmacología , Antioxidantes/farmacología , Compuestos de Bifenilo/química , Cromatografía Líquida de Alta Presión , Masculino , Malondialdehído/metabolismo , Óxido Nítrico/metabolismo , Estrés Oxidativo/efectos de los fármacos , Picratos/química , Extractos Vegetales/farmacología , Ratas , Ratas Wistar , Compuestos de Sulfhidrilo/metabolismo , Tolueno/análogos & derivados , Tolueno/metabolismo , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
A novel isoquinoline alkaloid, mahimbrine A, possessing a rare benzotropolone framing scaffold, was isolated from the endemic plant of Mahonia imbricata. Its structure was established on the basis of extensive spectroscopic analysis. A plausible biosynthetic route of mahimbrine A was proposed. Mahimbrine A showed no antimicrobial activity at the concentration of 1 mg/mL.
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Alcaloides/química , Biflavonoides/química , Catequina/análogos & derivados , Isoquinolinas/química , Mahonia/química , Alcaloides/síntesis química , Alcaloides/farmacología , Antiinfecciosos/farmacología , Espectroscopía de Resonancia Magnética con Carbono-13 , Catequina/química , Isoquinolinas/síntesis química , Isoquinolinas/farmacología , Pruebas de Sensibilidad Microbiana , Espectroscopía de Protones por Resonancia MagnéticaRESUMEN
Macrophages play an indispensable role in the host immune defense. Macrophages can undergo polarization into classically (M1) and alternatively (M2) activated macrophages. M1 macrophages activate immune and inflammatory response, while M2 macrophages are involved in tissue remodeling. Mahonia oiwakensis (Mo) is a herbal medicine in Asia used for its anti-inflammatory and analgesic properties; however, the mechanism is unclear. This study analyzed the effect of Mo extracts and its effects on the polarization of both macrophage RAW264.7 cells and mouse splenic macrophages. Water (Mo-W) and EtOH extracts (Mo-E) did not change the viability of RAW264.7 cells, whereas Mo-E inhibited nitric oxide (NO) production. The major compounds, berberine and palmatine, decreased the viability and NO levels of cells. The secretion of inflammatory cytokines CXCL16, IL-6, L-selectin, MCP1, RANTES, and sTNF-R1 was downregulated, whereas the production of vascular endothelial growth factor (VEGF) was upregulated by Mo-E, berberine, and palmatine treatments. Mo-E, berberine, and palmatine stimulated the expression of macrophage CD68 and M2-type CD204 markers, decreased M1-mediated p-STAT1 and NF-κB, and increased M2-mediated p-STAT6 expression. Similar effects on M2 polarization were also observed in splenic macrophages from mice. In conclusion, Mo-E, berberine, and palmatine modulated macrophages through the suppression of M1-mediated inflammation and the recruitment of M2-mediated VEGF secretion and STAT6 expression.
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Antiinflamatorios/farmacología , Macrófagos/efectos de los fármacos , Mahonia/química , Extractos Vegetales/farmacología , Factor de Transcripción STAT6/inmunología , Factor A de Crecimiento Endotelial Vascular/inmunología , Animales , Antiinflamatorios/aislamiento & purificación , Activación de Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Masculino , Ratones , Ratones Endogámicos BALB C , FN-kappa B/genética , FN-kappa B/inmunología , Extractos Vegetales/aislamiento & purificación , Células RAW 264.7 , Factor de Transcripción STAT1/genética , Factor de Transcripción STAT1/inmunología , Factor de Transcripción STAT6/genética , Factor A de Crecimiento Endotelial Vascular/genéticaRESUMEN
Herein, we propose a 1H NMR-based metabolomics method to reveal cytotoxic metabolites from Mahonia aquifolium stem-bark. Primary and secondary metabolites in the Mahonia aquifolium extracts were identified by thorough analysis of 1H and 2D NMR spectra, without prior isolation. An OPLS multivariate analysis method was used to correlate the chemical composition of the plant extracts with the results of cytotoxic activity against Human cervical adenocarcinoma cell line. Protoberberine alkaloids berberinе and palmatine, along with bisbenzylisoquinoline alkaloid berbamine were identified as the most influential in the OPLS model, with the highest cytotoxic activity.
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Mahonia/química , Metabolómica/métodos , Extractos Vegetales/farmacología , Espectroscopía de Protones por Resonancia Magnética/métodos , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/patología , Alcaloides/aislamiento & purificación , Alcaloides/farmacología , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos Fitogénicos/farmacología , Femenino , Células HeLa , Humanos , Corteza de la Planta , Extractos Vegetales/química , Neoplasias del Cuello Uterino/tratamiento farmacológico , Neoplasias del Cuello Uterino/patologíaRESUMEN
Granulomatous lobular mastitis (GLM) is a type of chronic mammary inflammation with unclear etiology. Currently systematic corticosteroids and methitrexate are considered as the main drugs for GLM treatment, but a high toxicity and risk of recurrence greatly limit their application. It is therefore an urgent requirement that safe and efficient natural drugs are found to improve the GLM prognosis. Broadleaf Mahonia (BM) is a traditional Chinese herb that is believed to have antiinflammatory properties according to ancient records of traditional Chinese medicine. The present study investigated this belief and demonstrated that BM significantly inhibited the expression of interleukin1ß (IL1ß), IL6, cyclooxygenase2 and inducible nitric oxide synthase in RAW264.7 cells, but had little influence on the cell viability, cell cycle and apoptosis. Meanwhile, the lipopolysaccharideinduced elevation of reactive oxygen species and nitric oxide was also blocked following BM treatment, accompanied with decreased activity of nuclear factorκB and MAPK signaling. A cytokine array further validated that BM exhibited significant inhibitory effects on several chemoattractants, including chemokine (CC motif) ligand (CCL)2, CCL3, CCL5 and secreted tumor necrosis factor receptor 1, among which CCL5 exhibited the highest inhibition ratio in cell and clinical GLM specimens. Collectively, the results show that BM is a novel effective antiinflammatory herb in vitro and ex vivo, and that CCL5 may be closely associated with GLM pathogenesis.
Asunto(s)
Quimiocina CCL5/genética , Medicamentos Herbarios Chinos/administración & dosificación , Mastitis Granulomatosa/tratamiento farmacológico , Inflamación/tratamiento farmacológico , Animales , Medicamentos Herbarios Chinos/química , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Mastitis Granulomatosa/genética , Mastitis Granulomatosa/patología , Humanos , Inflamación/complicaciones , Inflamación/genética , Inflamación/patología , Mahonia/química , Ratones , Células RAW 264.7 , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/efectos de los fármacosRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Mahonia bealei has a long history of medical use in traditional Chinese medicine for the treatment of inflammatory-associated diseases. Despite numerous phytochemical and pharmacological studies, there is a lack of systematic studies to understand the cellular and molecular mechanisms of the anti-inflammatory activity of this plant. AIM OF STUDY: This study aimed to evaluate the anti-inflammatory activity of the dichloromethane fraction from M. bealei leaves (MBL-CH). MATERIALS AND METHODS: RAW 264.7 cells were pretreated with different concentrations of MBL-CH for 30min prior to treatment with 1µg/ml of lipopolysaccharide (LPS). The nuclear factor κB (NF-κB) pathway and subsequent production of inflammatory mediators, such as nitric oxide (NO), prostaglandin E2 (PGE2), and tumour necrosis factor (TNF)-α were investigated. Furthermore, the in vivo mouse model of LPS-induced acute lung injury (ALI) was employed to study the anti-inflammatory effects of MBL-CH. RESULTS: Pre-treatment with MBL-CH significantly inhibited the LPS-stimulated secretion of NO, PGE2, and TNF-α into the culture medium, as well as the mRNA levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and TNF-α, which were associated with a reduction in the phosphorylation of IκBα, Akt, and PI3K and inhibition of the transcriptional activity of NF-κB. Furthermore, in vivo experiments revealed that MBL-CH attenuated LPS-stimulated lung inflammation in mice. CONCLUSION: Taken together, our findings indicate that MBL-CH attenuates LPS-stimulated inflammatory responses in macrophages by blocking NF-κB activation through interference with activation of the PI3K/Akt pathway, providing scientific evidence that the plant can be employed in traditional remedies.