RESUMEN
Systematic phytochemical investigation on the Mongolian medicinal herb Lomatogonium carinthiacum led to the isolation of 12 monoterpenoids including three new secoiridoids (1, 2 and 4) and one new iridoid glycoside (13), one new monoterpenoid alkaloid (3), and three new sesquiterpenoids (14-16). Comprehensive spectroscopic analysis (including 1D and 2D NMR, and HRESIMS) and quantum chemistry computations (including ECD and NMR calculations) were applied to elucidate their structures. Weak immunosuppressive activities were observed for the new isolates via inhibiting T cell proliferation and cytokine IFN-γ secretion in vitro.
Asunto(s)
Gentianaceae , Plantas Medicinales , Estructura Molecular , Medicina Tradicional Mongoliana , Glicósidos/química , Extractos Vegetales/química , Gentianaceae/químicaRESUMEN
Herbal treatments have been practiced by humans over centuries and therefore possess time-proven safety. However, it is crucial to evaluate the toxic effects of herbal medicine to confirm their safety, particularly when developing therapeutic drugs. Use of laboratory animals such as mice, rat, and rabbits was considered as gold standard in herbal toxicity assessments. However, in the last few decades, the ethical consideration of using higher vertebrates for toxicity testing has become more controversial. As a possible alternative model involving lower vertebrates such as zebra fish were introduced. Hence in the present study, swertiamain compound isolated from E. axillare was assessed for it antimicrobial activity in zebra fish larvae againt S. typhi. The cumulative mortality rate and bacterial localization in zebra fish larvae were studied. Biochemical markers assays were performed to find the preventive role of the compound during the typhoid infection. The results showed that zebra fish can be successfully used as a model to study typhoid infection and the anti-bacterial compound swertiamarin used in this study clears the bacterial load and pathogenic symptoms to a great extent.
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Gentianaceae , Fiebre Tifoidea , Ratas , Ratones , Humanos , Animales , Conejos , Pez Cebra , Salmonella typhi , Gentianaceae/químicaRESUMEN
SUMMARY: This study aimed to evaluate the effects of six weeks of HIIT on tissue and oxidative damage markers in rats supplemented with Coutoubea spicata fraction. Thirty-two male Wistar rats were divided into 4 groups: Baseline (GB); supplemented with 100 mg/kg of Coutoubea spicata fraction (GSCS); exercised for 6 weeks with the HIIT protocol (GH); supplemented with 100 mg/kg of Coutoubea spicata fraction + HIIT for 6 weeks (GHCS). Exercised animals performed the HIIT protocol (2 x 2). Tissue damage CK, LDH, ALT and AST markers in plasma were analyzed, as well as oxidative stress MDA and SH biomarkers in plasma and in cardiac, hepatic and muscle tissues. The results showed that CK, LDH, AST and ALT enzymes showed increase in GH when compared to GB (p<0.0001). However, CK, AST and ALT markers reduced their concentrations in GHCS when compared to GH (p<0.0001), indicating that Coutoubea spicata supplementation attenuated the damage in muscle and liver tissues induced by HIIT. Plasma, liver and muscle MDA showed increase in GH after HIIT sessions; however, when compared to GHCS, it showed reduced levels (p<0.0001). SH was elevated in the GH group when compared to GB in plasma and liver tissues (p<0.0001); in contrast, reduction in GHCS when compared to GH was observed in plasma, liver and cardiac tissues, demonstrating the redox effect of HIIT on some tissues. Thus, our findings showed that Coutoubea spicata has antioxidant activity, reducing oxidative damage markers and consequently tissue damage in healthy Wistar rats after HIIT protocol, but it also demonstrated redox balance after analyzing oxidative stress markers.
RESUMEN: Este estudio tuvo como objetivo evaluar los efectos de HIIT en los marcadores de daño tisular y oxidativo en ratas suplementadas con Coutoubea spicata durante seis semanas. Treinta y dos ratas Wistar macho se dividieron en 4 grupos: línea de base (GB); suplementados con 100 mg/kg de fracción de Coutoubea spicata (GSCS); ejercitados durante 6 semanas con el protocolo HIIT (GH); suplementado con 100 mg/kg de fracción de Coutoubea spicata + HIIT durante 6 semanas (GHCS). Los animales ejercitados realizaron el protocolo HIIT (2x2). Se analizaron los marcadores de daño tisular CK, LDH, ALT y AST en plasma, así como los biomarcadores de estrés oxidativo MDA y SH en plasma y en tejidos cardiaco, hepático y muscular. Los resultados indicaron que las enzimas CK, LDH, AST y ALT mostraron aumento en GH en comparación con GB (p<0,0001). Sin embargo, los marcadores CK, AST y ALT redujeron sus concentraciones en GHCS en comparación con GH (p<0,0001), lo que indica que la suplementación con Coutoubea spicata atenuó el daño en los tejidos musculares y hepáticos inducido por HIIT. La MDA de plasma, hígado y músculo mostró un aumento en la GH después de las sesiones de HIIT; sin embargo, en comparación con GHCS, mostró niveles reducidos (p<0,0001). Se observó SH elevado en el grupo de GH en comparación con GB en plasma y tejidos hepáticos (p<0,0001); en contraste, se observó una reducción en GHCS en comparación con GH en plasma, hígado y tejidos cardíacos, lo que demuestra el efecto redox de HIIT en algunos tejidos. Por lo tanto, nuestros hallazgos mostraron que Coutoubea spicata tiene actividad antioxidante, con reducción de los marcadores de daño oxidativo y, en consecuencia, el daño tisular en ratas Wistar sanas después del protocolo HIIT, pero además demostró el equilibrio redox después de analizar los marcadores de estrés oxidativo.
Asunto(s)
Animales , Masculino , Ratas , Extractos Vegetales/administración & dosificación , Estrés Oxidativo/efectos de los fármacos , Gentianaceae/química , Entrenamiento de Intervalos de Alta Intensidad , Biomarcadores , Ratas WistarRESUMEN
Swertiamarin, a seco-iridoid glycoside, is mainly found in Enicostemma littorale Blume (E. littorale) and exhibits therapeutic activities for various diseases. The present study aimed to provide a review of swertiamarin in terms of its phytochemistry, physicochemical properties, biosynthesis, pharmacology and therapeutic potential. Relevant literature was collected from several scientific databases, including PubMed, ScienceDirect, Scopus and Google Scholar, between 1990 and the present. This review included the distribution of swertiamarin in medicinal plants and its isolation, characterization, physicochemical properties and possible biosynthetic pathways. A comprehensive summary of the pharmacological activities, therapeutic potential and metabolic pathways of swertiamarin was also included after careful screening and tabulation. Based on the reported evidence, swertiamarin meets all five of Lipinski's rules for drug-like properties. Thereafter, the physicochemical properties of swertiamarin were detailed and analyzed. A simple and rapid method for isolating swertiamarin from E. littorale has been described. The present review proposed that swertiamarin may be biosynthesized by the mevalonate or nonmevalonate pathways, followed by the seco-iridoid pathway. It has also been found that swertiamarin is a potent compound with diverse pharmacological activities, including hepatoprotective, analgesic, anti-inflammatory, antiarthritis, antidiabetic, antioxidant, neuroprotective and gastroprotective activities. The anticancer activity of swertiamarin against different cancer cell lines has been recently reported. The underlying mechanisms of all these pharmacological effects are diverse and seem to involve the regulation of different molecular targets, including growth factors, inflammatory cytokines, protein kinases, apoptosis-related proteins, receptors and enzymes. Swertiamarin also modulates the activity of several transcription factors, and their signaling pathways in various pathological conditions are also discussed. Moreover, we have highlighted the toxicity profile, pharmacokinetics and possible structural modifications of swertiamarin. The pharmacological activities and therapeutic potential of swertiamarin have been extensively investigated. However, more advanced studies are required including clinical trials and studies on the bioavailability, permeability and administration of safe doses to offer swertiamarin as a novel candidate for future drug development.
Asunto(s)
Desarrollo de Medicamentos , Gentianaceae/química , Glucósidos Iridoides/farmacología , Pironas/farmacología , Animales , Descubrimiento de Drogas , Humanos , Glucósidos Iridoides/química , Glucósidos Iridoides/aislamiento & purificación , Extractos Vegetales/química , Extractos Vegetales/farmacología , Pironas/química , Pironas/aislamiento & purificaciónRESUMEN
The elusive targets and the multifactorial etiology of Parkinson's disease (PD) have hampered the discovery of a potent drug for PD. Furthermore, the presently available medications provide only symptomatic relief and have failed to mitigate the pathogenesis associated with PD. Therefore, the current study was aimed to evaluate the prospective of swertiamarin (SW), a secoiridoid glycoside isolated from a traditional medicinal plant, Enicostemma littorale Blume to ameliorate the characteristic features of PD in Caenorhabditis elegans. SW (25 µM) administration decreased the α-synuclein (α-syn) deposition, inhibited apoptosis and increased dopamine level mediated through upregulating the expression of genes linked to ceramide synthesis, mitochondrial morphology and function regulation, fatty acid desaturase genes along with stress responsive MAPK (mitogen-activated protein kinase) pathway genes. The neuroprotective effect of SW was evident from the robust reduction of 6-hydroxydopamine (6-OHDA) induced dopaminergic neurodegeneration independent of dopamine transporter (dat-1). SW mediated translational regulation of MAPK pathway genes was observed through increase expression of SKN-1 and GST-4. Further, in-silico molecular docking analysis of SW with C. elegans MEK-1 showed a promising binding affinity affirming the in-vivo results. Overall, these novel finding supports that SW is a possible lead for drug development against the multi- factorial PD pathologies.
Asunto(s)
Proteínas de Caenorhabditis elegans/metabolismo , Proteínas de Unión al ADN/metabolismo , Gentianaceae/química , Glucósidos Iridoides/farmacología , Fármacos Neuroprotectores/farmacología , Enfermedad de Parkinson/tratamiento farmacológico , Pironas/farmacología , Factores de Transcripción/metabolismo , alfa-Sinucleína/antagonistas & inhibidores , Animales , Apoptosis/efectos de los fármacos , Caenorhabditis elegans/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Humanos , Glucósidos Iridoides/química , Glucósidos Iridoides/aislamiento & purificación , Estructura Molecular , Fármacos Neuroprotectores/química , Fármacos Neuroprotectores/aislamiento & purificación , Enfermedad de Parkinson/metabolismo , Pironas/química , Pironas/aislamiento & purificación , Transducción de Señal/efectos de los fármacos , Relación Estructura-Actividad , alfa-Sinucleína/genética , alfa-Sinucleína/metabolismoRESUMEN
Gentianaceae family (such as Coutoubea spicata) contains iridoids and flavonoids with antidiabetic properties. However, there is no information available about the antidiabetic effects of C. spicata when combined with resistance exercise training (RET). This study evaluated the effects of the ethanolic extract (EE) and ethyl acetate fraction (EAF) of C. spicata on biochemical markers, muscle damage, and oxidative stress in diabetic rats submitted to RET. Alloxan-induced diabetic rats were distributed into 4 groups (each group, n = 8) treated with distilled water (TD), EE, EAF, or metformin and submitted to RET. Two groups without the disease (each group, n = 8) (sedentary control and trained control), as well as a sedentary diabetic group (n = 8) were included. Body weight and glycemia were evaluated weekly. After 30 days, lipid/lipoprotein profile, aspartate aminotransferase, alanine aminotransferase, muscle damage ((creatine kinase (CK) and lactate dehydrogenase (LDH)), and oxidative stress (malondialdehyde (MDA), sulfhydryl groups (SH), and ferric reducing antioxidant power) were evaluated. MDA and SH for pancreas, liver, heart, and muscle were evaluated. C. spicata extract and fraction combined with RET recovered body weight and reduced glycemia, muscle damage (CK: 36.83% and 21.45%; LDH: 49.83% and 68.55%), and low-density lipoprotein cholesterol (70.63%; 59.18%) and improved redox status (MDA: 50.33%, 39.74%; and SH: 53.97%; 76.41%), respectively, when compared with the TD group. C. spicata plus RET promoted anti-hyperglycemic, lipid-reducing, and antioxidant effects in diabetic rats. Novelty C. spicata presents anti-hyperglycemic and lipid-lowering effects potentiated by RET. C. spicata reduces muscle injury and increases antioxidant defense.
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Acetatos/química , Etanol/química , Gentianaceae/química , Hiperglucemia/tratamiento farmacológico , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/farmacología , Animales , Fraccionamiento Químico , Diabetes Mellitus Experimental , Enfermedades Musculares/tratamiento farmacológico , Condicionamiento Físico Animal , Componentes Aéreos de las Plantas , Extractos Vegetales/química , RatasRESUMEN
This study evaluated the effect of methanol and aqueous ethanol root extracts (200 mg/kg body weight) of Anthocleista djalonensis on sex hormone concentrations and testicular marker enzymes of adult rats after 60 days of administration followed by 60 days of treatment withdrawal. The results showed no significant changes in testosterone and follicle-stimulating hormone (FSH) levels during the 60 days of extract treatment. Interestingly, 60 days after treatment withdrawal, there was an increase in intratesticular and serum testosterone and serum FSH in the methanol but not aqueous ethanol extract post-treatment groups. Intratesticular 3ß-hydroxysteroid dehydrogenase (3ß-HSD) activity remained unaffected while that of 17ß-HSD increased slightly during treatment of both extracts and the increase reached a statistical significance level (p < .05) during post-treatment. Gamma-glutamyltranspeptidase activity in the testis of the methanol but not aqueous ethanol extract-treated animals remained high during post-treatment compared to initial treatment values. Phytochemical analysis of the plant extracts showed that phenol and flavonoid constituents were higher in the methanol than the aqueous ethanol extract and has higher antioxidant activity. Altogether, post-treatment effect of the extract on the testis was more effective than treatment-related effect and the methanol extract appears to have better and consistent effects on the investigated parameters probably due to higher antioxidant activity conferred to it by its phenolic and flavonoid contents.
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Hormona Folículo Estimulante/sangre , Gentianaceae/química , Extractos Vegetales/farmacología , Testículo/efectos de los fármacos , Testosterona/sangre , Animales , Peso Corporal/efectos de los fármacos , Evaluación Preclínica de Medicamentos , Masculino , Tamaño de los Órganos/efectos de los fármacos , Ratas Wistar , Testículo/enzimología , gamma-Glutamiltransferasa/metabolismoRESUMEN
A new lupane triterpenoid, 23-O-trans-feruloylcylicodiscic acid (1), as well as four known analogues (2â5), was isolated from the EtOAc fraction of Menyanthes trefoliata. The structure of compound 1 was elucidated on the basis of extensive spectroscopic analysis, including 2D NMR data. The structures of the known compounds were established by comparison of their spectroscopic data with that in the literature. Compounds 1, 2, and 4 exhibited certain anti-NO production activities.
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Antiinflamatorios no Esteroideos/química , Antiinflamatorios no Esteroideos/farmacología , Gentianaceae/química , Triterpenos Pentacíclicos/química , Triterpenos Pentacíclicos/farmacología , Triterpenos/química , Triterpenos/farmacología , Animales , Espectroscopía de Resonancia Magnética , Ratones , Estructura Molecular , Óxido Nítrico/antagonistas & inhibidores , Óxido Nítrico/biosíntesis , Extractos Vegetales/química , Extractos Vegetales/farmacología , Células RAW 264.7RESUMEN
A new naphthaldehyde derivative has been isolated from Comastoma pulmonarium by using various chromatographic techniques, including silica gel, Sephadex LH-20, MCI-gel resin and RP-HPLC. This compounds was determined as 5-methoxy-2-methyl-7-(2-oxopropyl)naphthalene-1-carbaldehyde(1) by NMR, MS, IR and UV spectra. This compound was also evaluated for its anti-tobacco mosaic virus (anti-TMV) activity. The result showed that it showed high anti-TMV activity with inhibition rate of 32.8%. The inhibition rate is close to that of positive control (ningnanmycin).
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Aldehídos/farmacología , Antivirales/farmacología , Gentianaceae/química , Naftalenos/farmacología , Virus del Mosaico del Tabaco/efectos de los fármacos , Aldehídos/aislamiento & purificación , Antivirales/aislamiento & purificación , Cromatografía Líquida de Alta Presión , Naftalenos/aislamiento & purificación , Fitoquímicos/aislamiento & purificación , Fitoquímicos/farmacología , NicotianaRESUMEN
Gentianopsis barbata, Halenia corniculata, and Gentianella acuta were widely distributed throughout China and commonly used in traditional Chinese medicine. However, owing to similar living environments and morphological features, locals often had trouble distinguishing between these three species. In this present study, chromatograms at 350 nm were obtained and the composition and content of their chemical compounds determined using HPLC-DAD/ESI-MS2. In total, 35 chemical compounds were detected, 32 of which were identified, 25 of which were xanthones, 6 flavonoids, and 1 chlorogenic acid. The 350 nm chromatograms of these three species displayed evident differences. The individual compounds and their occurrence and content in different parts of the plant within different species were included in our results. This basic data will be useful for future pharmacological study. The total compositions of flavonoids and xanthones were approximately comparable in G. barbata and H. corniculata. Meanwhile, xanthones were predominant in G. acuta. From the perspective of chemical compound compositions, the leaf is recommended as the most valuable medicinal section for each of these three species.
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Ácido Clorogénico/análisis , Medicamentos Herbarios Chinos/química , Flavonoides/análisis , Gentianaceae/química , Xantonas/análisis , Cromatografía Líquida de Alta Presión , Estructuras de las Plantas/química , Espectrometría de Masa por Ionización de ElectrosprayRESUMEN
In the present article, the facile green synthesis of silver nanoparticles (AgNPs) using aqueous leaf extract of Enicostemma axillare (Lam.) has reported. This is a simple, cost-effective, stable for a long time and reproducible aqueous synthesis method to obtain a self-assembly Ag nanoparticles. The size and shape of Ag nanoparticles were characterized by XRD, TEM, and SEM-EDS. The formation and stability of the reduced silver nanoparticles in the colloidal solution were monitored by UV-Vis spectrophotometer analysis. Zeta potential was confirmed by DLS study. The mean particle diameter of silver nanoparticles was calculated from the TEM, SEM and the size of the particles was measured between 15 and 20â¯nm. TEM analysis revealed the spherical shape of the particles. Crystalline nature of the nanoparticles in the face-centred cubic structure are confirmed by the peaks in the XRD pattern corresponding to (111), (200), (220) and (311) planes. This study showed the biogenic, environmentally friendly and cost-effective synthesis and characterization of the silver nanoparticles.
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Antiinfecciosos/síntesis química , Gentianaceae/química , Tecnología Química Verde , Nanopartículas del Metal/química , Hojas de la Planta/química , Humanos , Nanopartículas del Metal/ultraestructura , Tamaño de la Partícula , Extractos Vegetales/química , Plata , Soluciones , Agua/químicaRESUMEN
Swertia mussotii (Gentianaceae) is a traditional Chinese medicinal plant grown in the Qinghai-Tibet Plateau. Three fractions from S. mussotii extract, named SWF50, SWF 70 and SWF100, were screened for in vitro anti-proliferative activity on two gastric cancer cell lines, MGC-803 and BGC-823 cells using MTT assay. Our results demonstrated that SMF70 showed an anti-proliferative effect in MGC-803 cells and SMF100 showed an anti-proliferative effect in BGC-823 cells in vitro. Moreover, both two fractions induced apoptosis via depolymerization of cytoskeletal filaments, increased cytoplasmic levels of ROS and Ca2+ and disrupted mitochondrial transmembrane potential. In addition, flow cytometry analysis indicated that both two fractions could induce cell apoptosis and arrest the cell cycle at S phase. Our results indicate that SMF70 induces apoptosis of MGC-803 cells and SMF100 induces apoptosis of BGC-823 cells via a mitochondrial-dependent pathway. Meanwhile, we also investigated antitumor effect of SMF70 in vivo, and exhibited effective tumor growth inhibition. Our findings demonstrate that S. mussotii extracts could be a potential new alternative therapeutic agent gastric cancer.
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Apoptosis/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Extractos Vegetales/farmacología , Neoplasias Gástricas/tratamiento farmacológico , Swertia/química , Línea Celular Tumoral , Gentianaceae/química , Humanos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Plantas Medicinales/química , Estómago/efectos de los fármacosRESUMEN
Gentianaceae herb extracts have been widely used as food additives, teas or medicinal remedies for various diseases and disorders of the human body. Herein, the potential effects of iridoids, seco-iridoids and analog glycosides from gentian on acontine-induced hepatotoxicity were investigated in HepG2 cells to obtain metabolic data of drug-biotarget interactions. Molecular docking analysis was performed to assess the binding efficiencies of 53 iridoids, seco-iridoids and analog compounds obtained from 50 gentian species to the active sites of human CYP3A4 enzyme. The docking scores of 29 iridoids, seco-iridoids and 24 analog glycosides were calculated from the free energy of ligand-protein complexes using a computer-assisted docking simulation. After comprehensive evaluation, 6 of these compounds, i.e., gentiopicroside, sweroside, swertiamarin, loganic acid, 6-O-ß-d-glucosyl-gentiopicroside and amarogentin were selected to evaluate their hepatoprotective effects. Quantitative real-time PCR was used to measure the expression levels of CYP3A4 mRNA in HepG2 cells. Amarogentin displayed the most clear inductive effect on CYP3A4 mRNA levels in the HepG2 cells. Moreover, amarogentin was further studied for acontine-induced toxicity in the HepG2 cells to determine the potential mechanisms. Amarogentin displayed obvious inductive effect on CYP3A4 mRNA levels in the HepG2 cells. These results elucidated that the hepatoprotective effects were caused by the facilitation of drug metabolism, amelioration of mitochondrial dysfunction and reduction of oxidative stress. Our data demonstrated that the naturally found iridoids, seco-iridoids and analog glycosides in gentian may be responsible for the hepatoprotective effects of gentian-extracted compounds and thus, this study may be useful in the food industry or in clinical practice.
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Citocromo P-450 CYP3A/metabolismo , Gentianaceae/química , Glicósidos/farmacología , Iridoides/farmacología , Extractos Vegetales/farmacología , Sustancias Protectoras/farmacología , Citocromo P-450 CYP3A/genética , Glicósidos/química , Células Hep G2 , Humanos , Iridoides/química , Hígado/efectos de los fármacos , Hígado/metabolismo , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Simulación del Acoplamiento Molecular , Extractos Vegetales/química , Sustancias Protectoras/químicaRESUMEN
INTRODUCTION: Enicostema littorale blume (A. Raynal) is a traditional Indian plant belongs to the Gentianaceae family. A lot of research has been done on this plant for its antidiabetic activity. However, there are no reports on flavonoids from E. littorale for its antidiabetic activity and their mechanism of action. Thus, the aim of this study is to evaluate the antidiabetic activity of Swertisin rich flavonoid fraction (SRF) from Enicostema littorale blume and their mechanism of action. MATERIALS & METHODS: Type 2 Diabetes Mellitus rat model was established by inducing insulin resistance using high fat diet and low dose of streptozotacin injection and was authenticated by HOMA index. The antidiabetic effect of SRF was evaluated on diabetic rats to investigate its long term effects on fasting blood glucose, OGTT, weight of rats, insulin, liver profile, lipid profile, kidney profile, histopathology of liver and pancreas. In addition, antioxidant activity by lipid peroxidation and catalase assay, ex vivo assays and hepatic glycogen content were performed to determine its effect on glycogenesis and hepatic glucose production. Furthermore, the mechanism of action of SRF was evaluated by Real time PCR and the mRNA expression was quantified for Glucokinase (GCK), Insulin receptor substrate (IRS-1), Glucose transporter-2 (GLUT-2) and Glucose transporter-4 (GLUT-4) genes. RESULTS: Treatment of diabetic rats with SRF demonstrated significant (p<0.0001) dose dependant hypoglycemic activity as compared to positive control metformin group. A decrease in liver, lipid and kidney function tests was seen as compared to diabetic control indicating normalization of organ function tests. Also, antioxidant activity showed significant decrease in malondialdehyde (MDA) content in liver (p<0.001) as compared to pancreas and increased catalytic activity in liver, kidney, spleen and pancreas. The hepatic glycogen content was significantly (p<0.001) increased in SRF treated rats indicating its inhibition of hepatic glucose production. Furthermore, ex vivo assays showed the significant (p<0.05) increase in glucose uptake by diaphragm. The mRNA expression for GCK, IRS-1, GLUT-2 and GLUT-4 genes showed significant up regulation as compared to diabetic control indicating its mechanism via insulin signalling pathway. CONCLUSION: The studies suggest that SRF ameliorates the insulin resistance by increasing glucose uptake and sensitizing cells towards insulin via IRS1/PI3K/Akt2 pathway.
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Apigenina/farmacología , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Dieta Alta en Grasa/efectos adversos , Gentianaceae/química , Hiperglucemia/tratamiento farmacológico , Hiperlipidemias/tratamiento farmacológico , Animales , Antioxidantes/metabolismo , Apigenina/química , Diabetes Mellitus Experimental/inducido químicamente , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/inducido químicamente , Diabetes Mellitus Tipo 2/metabolismo , Flavonoides/farmacología , Glucosa/metabolismo , Hiperglucemia/metabolismo , Hiperlipidemias/metabolismo , Hipoglucemiantes/química , Hipoglucemiantes/farmacología , Insulina/metabolismo , Resistencia a la Insulina/fisiología , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Extractos Vegetales/farmacología , Ratas , Estreptozocina/farmacologíaRESUMEN
Herbal medicines were subjected to enzyme reaction by using a commercial glycosidase AMG-300L, and were evaluated for enhancement of their antioxidative activities. The methanolic extract of Gentianae Scabrae Radix (GSR) showed the most dramatic changes after enzyme reaction, as seen in the high-performance liquid chromatography profiles and an increase in the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging effect. Trifloroside (1, TF) was identified as being significantly decreased by enzyme reaction, whereas deglucosyltrifloroside (2, DTF) increased. The optimal reaction time to induce DTF was 24 h at 30°C. The content increased from 1.00 ± 0.29 mg/g of extract (gex) to 2.80 ± 0.85 mg/gex after 24 h of enzyme reaction. DTF showed better antioxidative effect than TF in the DPPH, Trolox equivalent antioxidant capacity, and reactive oxygen species (ROS) in HT22 cell assays. In addition, when HT22 cells were stressed by 5 mM glutamate, 50 µM of DTF significantly inhibited the glutamate-induced lactate dehydrogenase leakage, Ca2+ influx, lipid peroxidation, and intracellular ROS production. These data demonstrated that the enzyme-treated GSR and its increased level of antioxidant DTF could be useful as a starting point in the discovery of functional foods to prevent various oxidative stresses, especially neurodegenerative disorders.
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Antioxidantes/química , Antioxidantes/farmacología , Gentianaceae/química , Glucósidos/química , Glucósidos/farmacología , Glicósido Hidrolasas/química , Extractos Vegetales/química , Extractos Vegetales/farmacología , Aspergillus niger/enzimología , Línea Celular , Supervivencia Celular/efectos de los fármacos , Cromatografía Líquida de Alta Presión , Proteínas Fúngicas/química , Humanos , Peroxidación de Lípido/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Plantas Medicinales/química , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Diabetes mellitus has spread over the world with 347 million people affected. Insulin resistance is a main pathogenic event in Type 2 Diabetes Mellitus (T2DM) leading to a reduction in glucose uptake by peripheral tissue and increased hepatic glucose output. In this study, we have isolated four flavonoid rich fractions fraction A (FA), fraction B (FB), fraction C (FC) and fraction D (FD) from Enicostema littorale. All the fractions were preliminary screened for TLC fingerprinting, total flavonoid content. Total eight flavonoids were identified by LC/MS. Insulin resistant HepG2 (IR/HepG2) model was established by inducing insulin resistance in HepG2 cells to investigate the effect of these fractions on IR/HepG2 cell line for their glucose uptake. The results showed the significant dose dependant increase in glucose uptake of cells treated with FD. It showed significant activity at a concentration of 10µg/ml. The LC/MS results of FD demonstrated the presence of C-glycoside Swertisin which could be responsible for the effect. Further, to investigate the mechanism of action, gene expression for insulin receptor substrate 1 (IRS-1), protein kinase B (Akt-2) and glucose transporter 4 (GLUT-4) genes were evaluated by real time PCR. A significant upregulation of these genes was observed in FD treated samples, thereby indicating the enhancement of glucose uptake rate of cells via IRS-1/PI3K/Akt pathway.
Asunto(s)
Flavonoides/farmacología , Gentianaceae/química , Glucosa/metabolismo , Proteínas Sustrato del Receptor de Insulina/metabolismo , Resistencia a la Insulina/fisiología , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Línea Celular Tumoral , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Transportador de Glucosa de Tipo 4/metabolismo , Glicósidos , Células Hep G2 , Humanos , Insulina/metabolismo , Neoplasias Hepáticas , Monosacáridos/farmacología , Fosforilación/efectos de los fármacos , Extractos Vegetales/farmacología , Receptor de Insulina/metabolismo , Transducción de Señal/efectos de los fármacos , Regulación hacia Arriba/efectos de los fármacosRESUMEN
BACKGROUND: Aconitum brachypodum Diels (Family Ranunculaceae) is a Chinese ethnodrug and is well known for both its therapeutic application and high toxicity. However, no detoxication strategy is available for the complete elimination of the toxicity of Aconitum plants. Veratrilla baillonii Franch is believed to possess antitoxic effects on the toxicity induced by Aconitum plants and has been clinically used for hundreds of time by Naxi and Lisu nationalities in Yunnan Province of China. To further address the mechanism of the detoxication of Veratrilla baillonii, the effect of water decoction of Veratrilla baillonii (WVBF) on subacute toxicology of SD rats induced by Aconitum brachypodum (CFA), a genus Aconitum, was determined and studied in the present work. METHODS: The clinical behavior and number of survivors for different dosage of WVBF (25, 50, 100mg/kg) on CFA (4mg/kg) induced rats were observed until day 28. Histological changes and haematological parameters were evaluated. Moreover, Na+-K+-ATPase pathway in heart as well as key enzymes in liver were determined to further discuss the mechanism. RESULTS: The results showed that the exposure of CFA led to some subacute toxicity to rats, especially male ones, accompanied with abnormality of serum biochemical index in rats' serum. The toxicological target organs of CFA may be the heart, liver, kidney and brain. It is demonstrated that WVBF could attenuate the toxicity induced by Aconitum brachypodum via promoting the metabolic enzymes CYP3A1 and CYP3A2 in liver, downregulating the expression of Sodium/Calcium exchanger 1 (NCX1) and SCN5A sodium channal mRNA, and inducing Na+/K+-ATPase activity in heart. This study provides insights into detoxifying measures of Aconitum plants. CONCLUSIONS: Aconitum brachypodum may lead to subacute toxicity of rats after long term of administration, and the toxicity could be attenuated by Veratrilla baillonii via promoting the metabolic enzymes in liver, downregulating the expression of NCX1 and SCN5A mRNA, and inducing Na+/K+-ATPase activity in heart.
Asunto(s)
Aconitum/toxicidad , Gentianaceae/química , Extractos Vegetales/farmacología , Animales , China , Citocromo P-450 CYP3A/metabolismo , Regulación hacia Abajo/efectos de los fármacos , Femenino , Corazón/efectos de los fármacos , Inactivación Metabólica/efectos de los fármacos , Riñón/efectos de los fármacos , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Medicina Tradicional China , Ratas Sprague-Dawley , Intercambiador de Sodio-Calcio/metabolismo , ATPasa Intercambiadora de Sodio-Potasio/metabolismoRESUMEN
Mangiferin, a bioactive compound derived primarily from Anacardiaceae and Gentianaceae families and found in mangoes and honeybush tea, has been extensively studied for its therapeutic properties. Mangiferin has shown promising chemotherapeutic and chemopreventative potential. This review focuses on the effect of mangiferin on: (1) inflammation, with respect to NFκB, PPARÒ¯ and the immune system; (2) cell cycle, the MAPK pathway G2/M checkpoint; (3) proliferation and metastasis, and implications on ß-catenin, MMPs, EMT, angiogenesis and tumour volume; (4) apoptosis, with a focus on Bax/Bcl ratios, intrinsic/extrinsic apoptotic pathways and telomerase activity; (5) oxidative stress, through Nrf2/ARE signalling, ROS elimination and catalase activity; and (6) efficacy of chemotherapeutic agents, such as oxaliplatin, etoposide and doxorubicin. In addition, the need to enhance the bioavailability and delivery of mangiferin are briefly addressed, as well as the potential for toxicity.
Asunto(s)
Antineoplásicos/farmacología , Xantonas/farmacología , Anacardiaceae/química , Animales , Antineoplásicos/química , Apoptosis/efectos de los fármacos , Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Modelos Animales de Enfermedad , Sinergismo Farmacológico , Gentianaceae/química , Humanos , Inflamación/tratamiento farmacológico , Metástasis de la Neoplasia , Estrés Oxidativo , Extractos Vegetales/química , Extractos Vegetales/farmacología , Pruebas de Toxicidad , Xantonas/químicaRESUMEN
Two tetrahydroxanthones, 1,3,5S,8S-tetrahydroxy-5,6,7,8-tetrahydroxanthone (1) and 1,3,5R,8S-tetrahydroxy-5,6,7,8-tetrahydroxanthone (2), and six new tetrahydroxanthone glycosides, amarellins A-F (3-8), were isolated from the aerial parts of a Mongolian medicinal plant Gentianella amarella ssp. acuta (Gentianaceae). The structures of 1-8 were elucidated on the basis of spectroscopic analysis, chemical conversion, and ECD calculation. Amarellins A-C (3-5) were assigned as 8-O-ß-D-glucoside, 8-O-ß-D-xyloside, and 1-O-ß-D-glucoside of 1, respectively, while amarellins D-F (6-8) were elucidated to be 8-O-ß-D-xyloside, 1-O-ß-D-glucoside, and 3-O-ß-D-glucoside of 2, respectively.
Asunto(s)
Gentianella/química , Glucósidos/aislamiento & purificación , Glicósidos/aislamiento & purificación , Extractos Vegetales/química , Xantonas/aislamiento & purificación , Gentianaceae/química , Glucósidos/química , Glicósidos/química , Estructura Molecular , Mongolia , Componentes Aéreos de las Plantas , Plantas Medicinales/química , Xantonas/químicaRESUMEN
The major components, 1-hydroxy-2,3,5-trimethoxy-xanthone (HM-1) and 1,5-dihydroxy-2,3-dimethoxy-xanthone (HM-5) isolated from Halenia elliptica D. Don (Gentianaceae), could cause vasodilatation in rat coronary artery with different mechanisms. In this work, high-performance liquid chromatography coupled to ion trap time-of-flight mass spectrometry (LCMS-IT-TOF) was used to clarify the metabolic pathways, and CYP450 isoform involvement of HM-1 and HM-5 were also studied in rat. At the same time, in vivo inhibition effects of HM-1 and ethyl acetate extracts from origin herb were studied. Three metabolites of HM-5 were found in rat liver microsomes (RLMs); demethylation and hydroxylation were the major phase I metabolic reactions for HM-5. Multiple CYP450s were involved in metabolism of HM-1 and HM-5. The inhibition study showed that HM-5 inhibited Cyp1a2, 2c6 and 2d2 in RLMs. HM-1 inhibited activities of Cyp1a2, Cyp2c6 and Cyp3a2. In vivo experiment demonstrated that both HM-1 and ethyl acetate extracts could inhibit Cyp3a2 in rats. In conclusion, the metabolism of xanthones from the origin herb involved multiple CYP450 isoforms; in vitro, metabolism of HM-5 was similar to that of its parent drug HM-1, but their inhibition effects upon CYP450s were different; in vivo, Cyp3a2 could be inhibited by HM-1 and ethyl acetate extracts.