RESUMEN

Inflammation is increasingly recognized as a critical mediator of angiogenesis, and unregulated angiogenic responses often involve human diseases. The importance of regulating angiogenesis in inflammatory diseases has been demonstrated through some successful cases of anti-angiogenesis therapies in related diseases, including arthritis, but it has been reported that some synthetic types of antiangiogenic drugs have potential side effects. In recent years, the importance of finding alternative strategies for regulating angiogenesis has begun to attract the attention of researchers. Therefore, identification of natural ingredients used to prevent or treat angiogenesis-related diseases will play a greater role. Isookanin is a phenolic flavonoid presented in Bidens extract, and it has been reported that isookanin possesses some biological properties, including antioxidative and anti-inflammatory effects, anti-diabetic properties, and an ability to inhibit α-amylase. However, its antiangiogenic effects and mechanism thereof have not been studied yet. In this study, our results indicate that isookanin has an effective inhibitory effect on the angiogenic properties of microvascular endothelial cells. Isookanin shows inhibitory effects in multiple stages of PGE2-induced angiogenesis, including the growth, proliferation, migration, and tube formation of microvascular endothelial cells. In addition, isookanin induces cell cycle arrest in S phase, which is also the reason for subsequent inhibition of cell proliferation. The mechanism of inhibiting angiogenesis by isookanin is related to the inhibition of PGE2-mediated ERK1/2 and CREB phosphorylation. These findings make isookanin a potential candidate for the treatment of angiogenesis-related diseases.

Asunto(s)

Puntos de Control del Ciclo Celular/efectos de los fármacos , Chalconas/farmacología , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Dinoprostona/metabolismo , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Neovascularización Fisiológica/efectos de los fármacos , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Células Endoteliales/efectos de los fármacos , Células Endoteliales/metabolismo , Humanos , Modelos Biológicos , Fosforilación

RESUMEN

Acanthopanax henryi (Oliv.) Harms (Araliaceae), also known as Eleutherococcus henryi and Caoyewujia (Hengliwujia) in Chinese, is a widely used traditional Chinese herb with the effects of expelling wind and removing dampness, relaxing the muscles and stimulating the blood circulation, and regulating the flow of qi to alleviate pain in the theory of Traditional Chinese Medicine. Acanthopanax henryi (AH, thereafter) possesses ginseng-like activities and is known as ginseng-like herb. In the past decade, a great number of phytochemical and pharmacological studies on AH have been carried out. Several kinds of chemical compositions have been reported, including terpenoids (monoterpenoids, diterpenoids, and triterpenoid saponins), phenylpropanoids, caffeoyl quinic acid derivatives, flavonoids, lignans, sterols, fatty acids, etc., among which, triterpenoid saponins were considered to be the most active components. Considerable pharmacological experiments in vitro have demonstrated that AH possessed anti-neuroinflammatory, anti-adipogenic, anti-inflammatory, antibacterial, anti-cancer, anti-oxidation, anti-AChE, anti-BuChE, and antihyaluronidase activities. The present review is an up-to-date and comprehensive analysis of the botany, phytochemistry, and pharmacology of AH.

Asunto(s)

Eleutherococcus/química , Etnofarmacología , Fitoquímicos/análisis , Fitoquímicos/química , Fitoquímicos/aislamiento & purificación , Investigación

RESUMEN

Cynandione A (CA), isolated from ethyl acetate extract of Cynanchum wilfordii (CW), is a bioactive phytochemical that has been found to be beneficial for the treatment of several diseases. Hepatic de novo lipogenesis is one of the main causes of non-alcoholic fatty liver disease (NAFLD), which is thought to be a hepatic manifestation of certain metabolic syndromes. However, it has not yet been reported if CA has any therapeutic value in these diseases. Here, we investigated whether CA can inhibit hepatic lipogenesis induced by liver X receptor α (LXRα) using an in vitro model. We found that the extract and ethyl acetated layer of CW decreased the mRNA levels of sterol regulatory element-binding protein-1c (SREBP-1c), which plays a crucial role in hepatic lipogenesis. Additionally, we observed that CA could suppress the level of SREBP-1c, which was increased using two commercial LXRα agonists, GW3954 and T0901317. Moreover, the enzymes that act downstream of SREBP-1c were also inhibited by CA treatment. To understand the mechanism underlying this effect, the levels of phosphorylated AMP kinase (pAMPK) were measured after CA treatment. Therefore, CA might increase the pAMPK level by inducing phosphorylation of liver kinase B1 (LKB1), which can then convert AMPK to pAMPK. Taken together, we conclude that CA has an alleviative effect on hepatic lipogenesis through the stimulation of the LKB1/AMPK pathway.

Asunto(s)

Proteínas Quinasas Activadas por AMP/metabolismo , Compuestos de Bifenilo/farmacología , Cynanchum/química , Lipogénesis/efectos de los fármacos , Proteínas Serina-Treonina Quinasas/metabolismo , Quinasas de la Proteína-Quinasa Activada por el AMP , Animales , Células Hep G2 , Humanos , Hidrocarburos Fluorados/farmacología , Hígado/efectos de los fármacos , Receptores X del Hígado/metabolismo , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Fosforilación , Fitoquímicos/farmacología , Extractos Vegetales/farmacología , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/genética , Sulfonamidas/farmacología

RESUMEN

Acanthopanax gracilistylus (AGS) has long been used in traditional Chinese medicine for the treatment of various inflammatory diseases. 3­O­ß­D­glucopyranosyl 3α, 11α­dihydroxylup­20(29)­en­28­oic acid, acantrifoside A, acankoreoside D, acankoreoside B and acankoreoside A are major lupane­type triterpenoid saponins derived from AGS. In the present study, these five saponins were isolated from AGS by chromatography and their anti­inflammatory activities were investigated in lipopolysaccharide (LPS)­treated RAW264.7 macrophages. Cell viability was evaluated by MTT assay. Tumor necrosis factor (TNF)­α, interleukin (IL)­1ß and NF­κB p65 were measured by ELISA. The gene expression levels of TNF­α and IL­1ß was detected by reverse­transcription polymerase chain reaction. And high­mobility group box 1 (HMGB1) were analyzed by western blotting. The results demonstrated that these five saponins significantly suppressed LPS­induced expression of TNF­α and IL­1ß at the mRNA and protein level in RAW264.7 cells. Further analysis revealed that acankoreoside A and acankoreoside B were able to reduce the secretion of HMGB1 and NF­κB activity induced by LPS in RAW264.7 macrophages. Taken together, these results suggested that the anti­inflammatory activity of AGS­derived saponins may be associated with the downregulation of TNF­α and IL­1ß, and the 'late­phase' proinflammatory cytokine HMGB1, via negative regulation of the NF­κB pathway in RAW264.7 cells.

Asunto(s)

Proteína HMGB1/biosíntesis , Interleucina-1beta/biosíntesis , Lipopolisacáridos/inmunología , Macrófagos/efectos de los fármacos , Macrófagos/fisiología , Saponinas/farmacología , Triterpenos/farmacología , Factor de Necrosis Tumoral alfa/biosíntesis , Animales , Supervivencia Celular/efectos de los fármacos , Regulación de la Expresión Génica , Interleucina-1beta/genética , Ratones , FN-kappa B/metabolismo , Células RAW 264.7 , Factor de Necrosis Tumoral alfa/genética

RESUMEN

We investigated the anti-inflammatory effects of 3α-hydroxy-lup-20(29)-en-23, 28-dioic acid (HLEDA)-a lupane-type triterpene isolated from leaves of Acanthopanax gracilistylus W. W.Smith (AGS), as well as the underlying molecular mechanisms in lipopolysaccharide (LPS)-induced RAW264.7 cells. Our results demonstrated that HLEDA concentration-dependently reduced the production of nitric oxide (NO), significantly suppressed LPS-induced expression of TNF-α and IL-1ß at the mRNA and protein levels in RAW264.7 cells. Further analysis revealed that HLEDA could reduce the secretion of High Mobility Group Box 1 (HMGB1). Additionally, the results showed that HLEDA efficiently decreased nuclear factor-kappaB (NF-κB) activation by inhibiting the degradation and phosphorylation of IκBα. These results suggest that HLEDA exerts anti-inflammatory properties in LPS-induced macrophages, possibly through inhibition of the NF-κB signaling pathway, which mediates the expression of pro-inflammatory cytokines. These results warrant further studies that would concern candidate therapy for diseases, such as fulminant hepatitis and rheumatology of triterpenoids in AGS.

Asunto(s)

Antiinflamatorios/farmacología , Medicamentos Herbarios Chinos/química , Proteína HMGB1/antagonistas & inhibidores , Interleucina-1beta/antagonistas & inhibidores , Macrófagos/efectos de los fármacos , Triterpenos/farmacología , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Animales , Antiinflamatorios/aislamiento & purificación , Línea Celular , Relación Dosis-Respuesta a Droga , Eleutherococcus , Expresión Génica , Proteína HMGB1/genética , Proteína HMGB1/metabolismo , Inflamación , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Lipopolisacáridos/antagonistas & inhibidores , Lipopolisacáridos/farmacología , Macrófagos/citología , Macrófagos/metabolismo , Ratones , Inhibidor NF-kappaB alfa/antagonistas & inhibidores , Inhibidor NF-kappaB alfa/genética , Inhibidor NF-kappaB alfa/metabolismo , Óxido Nítrico/antagonistas & inhibidores , Óxido Nítrico/biosíntesis , Fosforilación/efectos de los fármacos , Triterpenos/aislamiento & purificación , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismo

RESUMEN

Triterpenoid saponins are difficult to analyze using high-performance liquid chromatography coupled to UV/vis spectrophotometry due to their lack of chromophores. This study describes the first analytical method for the determination of 15 triterpenoid saponins from the leaves, stems, root bark, and fruits of Acanthopanax henryi, using a high-performance liquid chromatography with charged aerosol detection coupled with electrospray ionization mass spectrometry method. The separation was carried out on a Kinetex XB-C18 column with an acetonitrile/water gradient as the mobile phase, followed by charged aerosol detection. The operating conditions of charged aerosol detection were set at 24 kPa for nitrogen pressure and 100 pA for the detection range. Liquid chromatography with electrospray ionization mass spectrometry is described for the identification of compounds in plant samples. The electrospray ionization mass spectrometry method involved the use of the [M + Na](+) and [M + NH4 ](+) ions for compounds 1-15 in the positive ion mode with an extracted ion chromatogram. The developed method was fully validated in terms of linearity, sensitivity, precision, repeatability, and recovery, then subsequently applied to evaluate the quality of A. henryi.

Asunto(s)

Aerosoles/análisis , Eleutherococcus/química , Saponinas/análisis , Triterpenos/análisis , Cromatografía Liquida , Espectrometría de Masa por Ionización de Electrospray

RESUMEN

Acanthopanax species are used in traditional medicine to treat numerous diseases. A simultaneous high-performance liquid chromatography (HPLC) method was developed and validated for the determination of the flavonoid and phenolic content of Acanthopanax leaves. HPLC analysis was performed on an AKZO NOBEL Kromasil 100-5C18 column (250 × 4.6 mm, 5 µm) using a gradient elution of acetonitrile-water containing 0.2% formic acid with a flow rate of 1.0 mL/min, monitored at 320 nm. The method was linear over the range 1-500 µg/mL (determination coefficients R(2) > 0.999). Satisfactory intraday and interday precision was achieved, with the relative standard deviation (RSD) <2.99%. The mean recoveries measured at the three concentrations were in the range of 90.11-104.83%, with RSD <2.91% for the targets. Twenty-four samples of Acanthopanax leaves from different species and locations were examined using this analytical method, and their chemical profiles provided information for the chemotaxonomic investigation. The established method is simple, rapid and reliable for the quality control of Acanthopanax leaves of various species from different collections. The complete phenolic and flavonoid profiles of Acanthopanax leaves of various species have been established.

Asunto(s)

Cromatografía Líquida de Alta Presión/métodos , Eleutherococcus/química , Flavonoides/análisis , Fenoles/análisis , Extractos Vegetales/química , Espectrofotometría Ultravioleta/métodos , Reproducibilidad de los Resultados

RESUMEN

In this study, we isolated scopoletin from Cirsium setidens Nakai (Compositae) and tested its effects on melanogenesis. Scopoletin was not toxic to cells at concentrations less than 50 µM and increased melanin synthesis in a dose-dependent manner. As melanin synthesis increased, scopoletin stimulated the total tyrosinase activity, the rate-limiting enzyme of melanogenesis. In a cell-free system, however, scopoletin did not increase tyrosinase activity, indicating that scopoletin is not a direct activator of tyrosinase. Furthermore, Western blot analysis showed that scopoletin stimulated the production of microphthalmia-associated transcription factor (MITF) and tyrosinase expression via cAMP response element-binding protein (CREB) phosphorylation in a dose-dependent manner. Based on these results, preclinical and clinical studies are needed to assess the use of scopoletin for the treatment of vitiligo.

RESUMEN

A novel aporphine alkaloid was isolated from the leaves of Epimedium koreanum Nakai during activity-guided fractionation in search of compounds with an anticholinesterase activity. The structure of the new compound was assigned as 1,10-methoxy-7-hydroxy-aporphine (1), which we have named epimediphine. Unambiguous (1)H-NMR and (13)C-NMR data for epimediphine are described. Epimediphine inhibited an acetylcholinesterase (AchE) activity in a dose-dependent manner with an IC50 value of 3.1 µM. Meanwhile, tacrine, dehydroevodiamine and physostigmine, which are therapeutic drugs or candidates for AD, exhibited an anti-AchE activity with IC50 values of 0.4, 37.9 and 0.12 µM, respectively.

Asunto(s)

Aporfinas/farmacología , Inhibidores de la Colinesterasa/química , Inhibidores de la Colinesterasa/farmacología , Epimedium/química , Acetilcolinesterasa/metabolismo , Alcaloides/química , Alcaloides/aislamiento & purificación , Alcaloides/farmacología , Aporfinas/química , Relación Dosis-Respuesta a Droga , Humanos , Concentración 50 Inhibidora , Espectroscopía de Resonancia Magnética , Fisostigmina/farmacología , Tacrina/farmacología

RESUMEN

Ginsenosides, which are active compounds found in ginseng (Panax ginseng), are used as antidiabetic treatments. The aim of this study was to determine whether Rb2, a type of ginsenoside, regulates hepatic gluconeogenesis through AMP-activated protein kinase (AMPK) and the orphan nuclear receptor small heterodimer partner (SHP) in hyperlipidemic conditions used as an in vitro model of type 2 diabetes. Considering these results, we concluded that Rb2 may inhibit palmitate-induced gluconeogenesis via AMPK-induced SHP by relieving ER stress, a cause of gluconeogenesis.

Asunto(s)

Proteínas Quinasas Activadas por AMP/metabolismo , Ginsenósidos/farmacología , Hipoglucemiantes/farmacología , Fosforilación/efectos de los fármacos , Animales , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Silenciador del Gen/efectos de los fármacos , Ginsenósidos/metabolismo , Gluconeogénesis/efectos de los fármacos , Glucosa/análisis , Glucosa/biosíntesis , Hepatocitos/efectos de los fármacos , Hipoglucemiantes/metabolismo , Hígado/efectos de los fármacos , Hígado/metabolismo , Proteína Tirosina Fosfatasa no Receptora Tipo 6/efectos de los fármacos , ARN/análisis , Ratas , Transfección

RESUMEN

Clerodendron trichotomum leaves and Rumex aquatica herbs are used as a folk medicine for the treatment of inflammatory diseases, but their active ingredients are not known until now. We isolated caffeic acid and phenylpropanoid glycosides, 1-O-caffeoyl glycoside and acteoside [ß-(3',4'-dihydroxyphenyl) ethyl-O-α-l-rhamnopyranosyl(1→3)-ß-d-(4-O-caffeoyl)-glucopyranoside] from their ethylacetate fractions, respectively, and evaluated their anti-asthmatic effects on the aerosolized ovalbumin (OA) challenge in the OA-sensitized guinea-pigs measuring the specific airway resistance (sRaw) during the immediate-phase response (IAR) and late-phase response (LAR), and also measured recruitment of leukocytes and chemical mediators on the bronchoalveolar lavage fluids (BALF) in LAR, as well as histopathological survey. Acteoside and 1-O-caffeoyl glycoside (25mg/kg) significantly (P<0.05) inhibited sRaw by 32.14 and 26.79% in IAR, and by 55.88% and 52.94% in LAR, respectively, whereas caffeic acid (25mg/kg) inhibited sRaw by 30.36% in IAR and 44.12% in LAR, compared to control, but with less effective than dexamethasone, disodium cromoglycate, and salbutamol, respectively. In addition, phenylpropanoid glycosides (25mg/kg) significantly inhibited the recruitments of leukocytes, particularly neutrophils and eosinophils into lung, Furthermore, 1-O-caffeoyl glycoside, acteoside and caffeic acid significantly (P<0.05) inhibited protein content at a dose of 25mg/kg, and histamine content and PLA(2) activity at a dose of 50mg/kg, in BALF. Acteoside had more active than caffeic acid and 1-O-caffeoyl glycoside. However, their anti-asthmatic effects were less than the reference drugs. These results indicated that caffeic acid and its glycosides (25mg/kg) have anti-asthmatic effect as the same manner with dexamethasone and disodium cromoglycate.

Asunto(s)

Antiasmáticos/uso terapéutico , Asma/tratamiento farmacológico , Clerodendrum/química , Glicósidos/uso terapéutico , Fenoles/uso terapéutico , Fitoterapia , Rumex/química , Resistencia de las Vías Respiratorias/efectos de los fármacos , Albuterol/farmacología , Albuterol/uso terapéutico , Animales , Antiasmáticos/farmacología , Asma/metabolismo , Asma/patología , Líquido del Lavado Bronquioalveolar , Ácidos Cafeicos/farmacología , Ácidos Cafeicos/uso terapéutico , Cromolin Sódico/farmacología , Cromolin Sódico/uso terapéutico , Dexametasona/farmacología , Dexametasona/uso terapéutico , Glucósidos/farmacología , Glucósidos/uso terapéutico , Glicósidos/farmacología , Cobayas , Histamina/metabolismo , Leucocitos/efectos de los fármacos , Pulmón/efectos de los fármacos , Pulmón/patología , Masculino , Infiltración Neutrófila/efectos de los fármacos , Ovalbúmina , Fenoles/farmacología , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Hojas de la Planta , Propanoles/farmacología , Propanoles/uso terapéutico , Proteínas/metabolismo

RESUMEN

The chromatographic separation of MeOH extract from the Quercus salicina Blume Stem led to the isolation of five phenolic compounds. Using spectroscopic methods, the structures of these compounds were determined as D-threo-guaiacylglycerol 8-O-beta-D-(6'-O-galloyl)glucopyranoside (1), 9-methoxy-D-threo-guaiacylglycerol 8-O-beta-D-(6'-O-galloyl)glucopyranoside (2), 6''-O-galloyl salidroside (3), methyl gallate (4), quercetin (5). We measured radical scavenging activity with the DPPH method and the anti-lipid peroxidative efficacy on human LDL with TBARS assay, with the result that all these compounds exhibited the antioxidative activity.

Asunto(s)

Antioxidantes/farmacología , Depuradores de Radicales Libres/farmacología , Peroxidación de Lípido/efectos de los fármacos , Quercus , Antioxidantes/química , Antioxidantes/aislamiento & purificación , Compuestos de Bifenilo , Cromatografía , Depuradores de Radicales Libres/química , Depuradores de Radicales Libres/aislamiento & purificación , Ácido Gálico/análogos & derivados , Ácido Gálico/farmacología , Glucósidos/farmacología , Glicerol/análogos & derivados , Glicerol/farmacología , Humanos , Lipoproteínas LDL/metabolismo , Espectroscopía de Resonancia Magnética , Picratos/química , Tallos de la Planta , Quercetina/farmacología , Quercus/química , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismo