RESUMEN
A naturally occurring stilbene, resveratrol, shows promising effects in the treatment of malignant pleural mesothelioma (MPM) both as a single agent and in combination with chemotherapeutic drugs. To discover new anticancer agents targeting MPM, stilbene-targeted isolation was performed on the roots of Polygonum multiflorum Thunb., an herbal medicine rich in stilbene compounds. In this study, seven stilbene glycosides (1-7) were isolated, along with four non-stilbenes (8-11), of which compounds 4 and 9-11 have not previously been isolated from this species. Stiquinoside A (1) is a previously undescribed stilbene glycoside, and its structure was elucidated as (E)-2,3,5,4'-tetrahydroxystilbene 2-O-ß-d-quinovopyranoside based on 1D and 2D-NMR, HR-ESI-MS, and acid hydrolysis experiments. Compounds 1, 4, 6, and 8 significantly inhibit the growth of MPM cancer cells H2452. These results demonstrate the potential utility of stilbenes in new strategies for the treatment of MPM.
Asunto(s)
Antineoplásicos Fitogénicos , Fallopia multiflora , Mesotelioma Maligno , Raíces de Plantas , Estilbenos , Humanos , Estilbenos/farmacología , Estilbenos/aislamiento & purificación , Raíces de Plantas/química , Estructura Molecular , Línea Celular Tumoral , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/aislamiento & purificación , Mesotelioma Maligno/tratamiento farmacológico , Fallopia multiflora/química , Fitoquímicos/farmacología , Fitoquímicos/aislamiento & purificación , Glicósidos/farmacología , Glicósidos/aislamiento & purificación , Mesotelioma/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , ChinaRESUMEN
This work offered a productive technique for resveratrol extraction from Polygonum Cuspidatum (P. Cuspidatum) using ionic liquids in synergy with ultrasound-enzyme-assisted extraction (UEAE). Firstly, ionic liquids with different carbon chains and anions were evaluated. Subsequently, a comprehensive investigation was carried out to evaluate the effect of seven crucial parameters on the resveratrol yield: pH value, enzyme concentration, extraction temperature, extraction time, ultrasonic power, concentration of ionic liquid (IL concentration) and the liquid-solid ratio. Employing the Plackett-Burman Design (PBD), the critical factors were effectively identified. Building upon this foundation, the process was further optimized through the application of Response Surface Methodology (RSM) and an Artificial Neural Network-Genetic Algorithm (ANN-GA). The following criteria were determined to be the ideal extraction conditions: an enzyme concentration of 2.18%, extraction temperature of 58 °C, a liquid-solid ratio of 29 mL/g, pH value of 5.5, extraction time of 30 min, ultrasonic power of 250 W, and extraction solvent of 0.5 mol/L 1-butyl-3-methylimidazolium bromide. Under these conditions, the resveratrol yield was determined to be 2.90 ± 0.15 mg/g. Comparative analysis revealed that the ANN-GA model provided a better fit to the experimental data of resveratrol yield than the RSM model, suggesting superior predictive capabilities of the ANN-GA approach. The introduction of a novel green solvent system in this experiment not only simplifies the extraction process but also enhances safety and feasibility. This research paves the way for innovative approaches to extracting resveratrol from botanical sources, showcasing its significant potential for a wide range of applications.
Asunto(s)
Fraccionamiento Químico , Fallopia japonica , Líquidos Iónicos , Resveratrol , Resveratrol/aislamiento & purificación , Resveratrol/química , Líquidos Iónicos/química , Fallopia japonica/química , Fraccionamiento Químico/métodos , Temperatura , Ondas Ultrasónicas , Concentración de Iones de Hidrógeno , Estilbenos/aislamiento & purificación , Estilbenos/química , Enzimas/metabolismoRESUMEN
Piceatannol, resveratrol's derivative, and a valuable polyphenol has managed to become one of the most remarkable candidate molecules for drug development research, with its high bioactive properties and higher stability. On the other hand, the very low amount of piceatannol in plants which are its natural source increases the cost and limits the commercialization possibilities of the product. To overcome this bottleneck, a limited number of studies have recently shown that it is possible to produce piceatannol from the resveratrol precursor much cheaper by regioselective hydroxylation catalyzed by bacteria isolated from the soil, and the search for new bacteria of similar nature in new ecosystems has gained popularity. The aim of our study, which was prepared within this framework, is the bacterial isolate with regioselective hydroxylation potential obtained as a result of selective isolation steps; determination of resveratrol hydroxylation potentials and piceatannol product yields, investigation of possibilities to increase piceatannol yield with optimization trials and identification of isolates with the highest yield. For this purpose, 200 bacterial isolates capable of resveratrol hydroxylation were obtained from soil samples taken from Erzurum (Turkey) and its surroundings by using selective media. In the continuation of the study; resveratrol hydroxylation trials were carried out with these isolates and 55 active isolates capable of producing piceatannol by regioselective hydroxylation were selected. Then, yield improvement studies of active isolates were carried out by using different carbon sources and optimizing the culture conditions. As a result, a culture collection was created by identifying the 6 most active bacterial isolates with commercialization potential using conventional and molecular methods. These are 4 Gram-positive (Rhodococcus sp., Rhodococcus erythropolis, Paeniglutamicibacter sp., Arthrobacter sp.) and 2 Gram-negative (Shinella sp., Ensifer adhaerens) bacterial isolates. As a result of the optimization studies, three of these isolates used phenol as a biocatalyst, while the other three increased the production yield of piceatannol by using 4-hydroxyphenylacetic acid.
Asunto(s)
Bacterias , Resveratrol , Microbiología del Suelo , Estilbenos , Estilbenos/metabolismo , Estilbenos/aislamiento & purificación , Bacterias/metabolismo , Bacterias/aislamiento & purificación , Bacterias/clasificación , Resveratrol/metabolismo , Turquía , HidroxilaciónRESUMEN
In this study, four undescribed bibenzyl derivatives (1-4), together with seven known compounds (5-11) were isolated from the aerial parts of Dendrobium officinale. Their chemical structures were determined to be (7'S,8'S) -9''-acetyldendrocandin U (1), (7'S,8'S) -4'-methoxydendrocandin T (2), (7'R,8'S) -dendrocandin B (3), (1S,2R) -5'''-methoxydendrofindlaphenol C (4) by analyzing of the spectroscopic data including HR-ESI-MS, 1D-, and 2D-NMR spectra. The absolute configurations of compounds 1-4 were determined by the electronic circular dichroism (ECD) spectra. Compounds 1-3, 5, 10 and 11 inhibited α-glucosidase with the IC50 values ranging from 56.3 to 165.3â µM, compounds 1-3, 5, 7-10 inhibited α-amylase with the IC50 values ranging from 65.2 to 177.6â µM.
Asunto(s)
Dendrobium , Inhibidores de Glicósido Hidrolasas , Componentes Aéreos de las Plantas , alfa-Amilasas , alfa-Glucosidasas , Dendrobium/química , alfa-Amilasas/antagonistas & inhibidores , alfa-Amilasas/metabolismo , alfa-Glucosidasas/metabolismo , Inhibidores de Glicósido Hidrolasas/farmacología , Inhibidores de Glicósido Hidrolasas/química , Inhibidores de Glicósido Hidrolasas/aislamiento & purificación , Componentes Aéreos de las Plantas/química , Estilbenos/química , Estilbenos/farmacología , Estilbenos/aislamiento & purificación , Relación Estructura-Actividad , Estructura Molecular , Conformación MolecularRESUMEN
The isolation of previously undescribed 12 compounds from the MeOH extract of Jacobaea vulgaris whole plants is disclosed, comprising 11 dihydrostilbenes (1-11) and one flavanone (12), and eight known compounds (six flavonoids, one dihydrostilbene, and one caffeoylquinic acid). Structural elucidation employed spectroscopic methods, including 1D and 2D NMR spectroscopy, HRESIMS, and ECD calculations. Evaluation of the compounds' effects on PCSK9 and LDLR mRNA expression revealed that compounds 1 and 3 downregulated PCSK9 mRNA while increasing LDLR mRNA expression, suggesting potential cholesterol-lowering properties.
Asunto(s)
Flavonoides , Estilbenos , Flavonoides/química , Flavonoides/aislamiento & purificación , Flavonoides/farmacología , Estilbenos/química , Estilbenos/aislamiento & purificación , Estilbenos/farmacología , Estructura Molecular , Proproteína Convertasa 9/metabolismo , Proproteína Convertasa 9/genética , Humanos , Receptores de LDL/metabolismo , ARN Mensajero/metabolismo , ARN Mensajero/genéticaRESUMEN
Three Diels-Alder type adducts (1-3) along with their precursors, including one 2-arylbenzofuran (4) and one stilbene (5), were isolated from the MeOH extract of M. alba var. shalun root cultures. Among them, 1 is a new Diels-Alder type adduct named morushalunin D. The molecular structures of 1-5 were elucidated based on spectroscopic data and comparison with the literatures. Cytotoxic properties of compounds 1-5 were evaluated against murine leukemia P-388 cells. Morushalunin D (1), mulberrofuran T (2), sorocein A (3), moracin M (4), and oxyresveratrol (5) were active, significantly inhibiting the growth of P-388 cells with IC50 values of 0.5, 1.0, 0.6, 2.0, and 3.3 µg/ml, respectively.
Asunto(s)
Morus , Raíces de Plantas , Estilbenos , Morus/química , Raíces de Plantas/química , Estructura Molecular , Ratones , Animales , Estilbenos/química , Estilbenos/farmacología , Estilbenos/aislamiento & purificación , Benzofuranos/química , Benzofuranos/farmacología , Benzofuranos/aislamiento & purificación , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/química , Ensayos de Selección de Medicamentos AntitumoralesRESUMEN
The schweinfurthin family of natural compounds exhibit a unique and potent differential cytotoxicity against a number of cancer cell lines and may reduce tumor growth in vivo. In some cell lines, such as SF-295 glioma cells, schweinfurthins elicit cytotoxicity at nanomolar concentrations. However, other cell lines, like A549 lung cancer cells, are resistant to schweinfurthin treatment up to micromolar concentrations. At this time, the precise mechanism of action and target for these compounds is unknown. Here, we employ RNA sequencing of cells treated with 50 nM schweinfurthin analog TTI-3066 for 6 and 24 h to elucidate potential mechanisms and pathways which may contribute to schweinfurthin sensitivity and resistance. The data was analyzed via an interaction model to observe differential behaviors between sensitive SF-295 and resistant A549 cell lines. We show that metabolic and stress-response pathways were differentially regulated in the sensitive SF-295 cell line as compared with the resistant A549 cell line. In contrast, A549 cell had significant alterations in response genes involved in translation and protein metabolism. Overall, there was a significant interaction effect for translational proteins, RNA metabolism, protein metabolism, and metabolic genes. Members of the Hedgehog pathway were differentially regulated in the resistant A549 cell line at both early and late time points, suggesting a potential mechanism of resistance. Indeed, when cotreated with the Smoothened inhibitor cyclopamine, A549 cells became more sensitive to schweinfurthin treatment. This study therefore identifies a key interplay with the Hedgehog pathway that modulates sensitivity to the schweinfurthin class of compounds.
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Neoplasias Encefálicas/tratamiento farmacológico , Metabolismo Energético/efectos de los fármacos , Euphorbiaceae , Glioma/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , RNA-Seq , Estilbenos/farmacología , Células A549 , Antineoplásicos Fitogénicos/aislamiento & purificación , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patología , Relación Dosis-Respuesta a Droga , Resistencia a Antineoplásicos , Metabolismo Energético/genética , Euphorbiaceae/química , Regulación Neoplásica de la Expresión Génica , Glioma/genética , Glioma/metabolismo , Glioma/patología , Proteínas Hedgehog/genética , Proteínas Hedgehog/metabolismo , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Prenilación , Transducción de Señal , Estilbenos/aislamiento & purificación , Transcripción Genética , TranscriptomaRESUMEN
Pinosylvin stilbenes are phenolic compounds mainly occurring in the Pinaceae family. We previously reported that the accumulation of two pinosylvin stilbene compounds, dihydropinosylvin methyl ether (DPME) and pinosylvin monomethyl ether (PME), in Pinus strobus trees was highly enhanced by infection with pine wood nematodes (PWNs: Bursaphelenchus xylophilus), and these two compounds showed strong nematicidal activity against PWNs. In this work, we established a system of pinosylvin stilbene (DPME and PME) production via the in vitro culture of P. strobus calli, and we examined the nematicidal activity of callus extracts. Calli were induced from the culture of mature zygotic embryos of P. strobus. Optimized growth of calli was obtained in 1/2 Litvay medium with 1.0 mg/L 2,4-D and 0.5 mg/L BA. DPME and PME accumulation did not occur in nonaged (one-month-old) calli but increased greatly with prolonged callus culture. The concentrations of DPME and PME in three-month-old dark-brown calli were 6.4 mg/g DW and 0.28 mg/g DW, respectively. The effect of methyl jasmonate treatment on the accumulation of DPME and PME was evaluated in cell suspension culture of P. strobus. However, the treatment appeared to show slight increase of DPME accumulation compared to callus browning. A test solution prepared from crude ethanol extracts from aged calli (three months old) containing 120 µg/ml DPME and 5.16 µg/ml PME treated with PWNs resulted in 100% immobilization of the adult PWNs and 66.7% immobilization of the juvenile PWNs within 24 h. However, nonaged callus extracts did not show any nematicidal activity against juvenile PWNs and showed less than 20% nematicidal activity against adult PWNs. These results indicate that pinosylvin stilbenes can be effectively produced by prolonged culture of P. strobus calli, can be isolated using simple ethanolic extraction, and are applicable as beneficial eco-friendly compounds with nematicidal activity against PWNs.
Asunto(s)
Antinematodos/aislamiento & purificación , Antinematodos/farmacología , Nematodos/efectos de los fármacos , Pinus/metabolismo , Estilbenos/farmacología , Animales , Células Cultivadas , Etanol , Estilbenos/aislamiento & purificación , Estilbenos/metabolismo , Factores de TiempoRESUMEN
The cumulative effects of cell damage result in aging, which gradually decreases human function in various aspects and leads to multiple age-related chronic diseases. To overcome the adverse effects of aging, silent mating type information regulation 2 homologue (SIRT1) activators are promising bioactive compounds that mimic calorie restriction to improve quality of life and prevent aging. In this study, 11 new flavonostilbenes (1-11) and three known compounds (12-14) were purified from stems of Rhamnoneuron balansae. The structures of the new compounds were determined using extensive data from spectroscopic methods, including NMR and HRESIMS. Their absolute configurations were deduced by ECD calculations with coupling constant analysis. All of the isolated new compounds (1-11) were evaluated for their effects on SIRT1 deacetylase activity, the NAD+/NADH ratio, and the AMP-activated protein kinase activation level in cell-based assays. The results showed that rhamnoneuronal D (1) exhibits promising biological activity in several in vitro models related to SIRT1 and suggest it is a potential natural-product-based antiaging agent.
Asunto(s)
Tallos de la Planta/química , Sirtuina 1/efectos de los fármacos , Estilbenos/aislamiento & purificación , Adenilato Quinasa/metabolismo , Animales , Espectroscopía de Resonancia Magnética con Carbono-13 , Activación Enzimática , Humanos , NAD/metabolismo , Espectroscopía de Protones por Resonancia Magnética , Espectrometría de Masa por Ionización de Electrospray , Estilbenos/farmacología , Thymelaeaceae/químicaRESUMEN
The first natural product isolation studies of Nothofagus gunnii (Hook.f.) Oerst and Nothofagus cunninghamii (Hook.f.) Oerst have been undertaken. A previously unreported stilbene derivative, pinosylvin monoacetate, was isolated from the leaves of N. gunnii, in addition to 14 known compounds; including the flavonoids galangin, pinobanksin, catechin and quercetin; sesquiterpenoids such as, ilicol and (+)-ß-costol acetate; 2,4-dihydroxy-6-methoxychalcone and pinosylvin. Four known flavonoid natural products, catechin, quercetin, ayanin, and avicularin were isolated from the leaves of N. cunninghamii. This study reveals that N. gunnii is a rich source of flavonoid, chalcone and stilbene compounds, while primarily hydroxyflavonoid compounds are found in N. cunninghamii. The isolated phytochemicals are consistent with the evolutionary relationships suggested to exist among Nothofagus species.
Asunto(s)
Productos Biológicos/aislamiento & purificación , Fagales/química , Extractos Vegetales/aislamiento & purificación , Productos Biológicos/química , Flavonoides/aislamiento & purificación , Espectroscopía de Resonancia Magnética , Extractos Vegetales/química , Hojas de la Planta/química , Estilbenos/aislamiento & purificación , Tasmania , Terpenos/aislamiento & purificación , VictoriaRESUMEN
Peanut produces prenylated stilbenoids upon biotic stress. However, the role of these compounds against oxidative stress have not been thoroughly elucidated. To this end, the antioxidant capacity of extracts enriched in prenylated stilbenoids and derivatives was studied. To produce these extracts, hairy root cultures of peanut cultivars Hull, Tifrunner, and Georgia Green were co-treated with methyl jasmonate, cyclodextrin, hydrogen peroxide, and magnesium chloride and then the stilbenoids were extracted from the culture medium. Among the three cultivars, higher levels of the stilbenoid derivatives arachidin-1 and arachidin-6 were detected in cultivar Tifrunner. Upon reaction with 2,2-diphenyl-1picrylhydrazyl, extracts from cultivar Tifrunner showed the highest antioxidant capacity with an IC50 of 6.004 µg/mL. Furthermore, these extracts had significantly higher antioxidant capacity at 6.25 µg/mL and 3.125 µg/mL when compared to extracts from cultivars Hull and Georgia Green. The stilbenoid-rich extracts from peanut hairy roots show high antioxidant capacity and merit further study as potential nutraceuticals to promote human health.
Asunto(s)
Arachis/metabolismo , Estrés Oxidativo/fisiología , Estilbenos/metabolismo , Antioxidantes/análisis , Antioxidantes/farmacología , Medios de Cultivo , Ácidos Eicosanoicos , Fabaceae/metabolismo , Humanos , Extractos Vegetales/farmacología , Raíces de Plantas/metabolismo , Prenilación de Proteína/fisiología , Estilbenos/química , Estilbenos/aislamiento & purificación , Estrés Fisiológico/fisiologíaRESUMEN
Twenty-two flavonoids and stilbenes (1-22) were obtained from the leaf of Morus alba var. multicaulis. Among them, morusalbanosides A (1), B1 (2), and B2 (3) were new compounds. Moreover, compounds 1, 3, 4-11, 15-18, and 22 displayed inhibitory effects on triglyceride (TG) accumulation in HepG2 cells in a concentration dependent manner. Furthermore, compounds 1, 3, 11, and 22 could activate the phosphorylation of AMP-activated protein kinase α (AMPKα), reduce the synthesis of TG by inhibiting the expression of fatty acid synthase (FAS) and stearoyl-CoA desaturase 1 (SCD1). While, only compounds 1 and 11 could promote the phosphorylation of acetyl-CoA carboxylase 1 (ACC1) and accelerate the oxidation of fatty acids by up-regulating carnitine palmitoyltransferase 1A (CPT1A). In brief, this study found that most of the researched flavonoids and stilbenes could regulate TG metabolism in vitro. They might play the role by up-regulating phosphorylation of AMPKα, inhibiting TG biosynthesis, and promoting the oxidation of fatty acids.
Asunto(s)
Flavonoides/farmacología , Metabolismo de los Lípidos/efectos de los fármacos , Morus/química , Estilbenos/farmacología , Proteínas Quinasas Activadas por AMP/metabolismo , China , Flavonoides/aislamiento & purificación , Células Hep G2 , Humanos , Estructura Molecular , Fosforilación/efectos de los fármacos , Fitoquímicos/aislamiento & purificación , Fitoquímicos/farmacología , Hojas de la Planta/química , Estilbenos/aislamiento & purificación , Triglicéridos/metabolismoRESUMEN
Eight new stilbene dimer xylosides (1-8) and one new flavanol (9), along with seven known ones (10-16) were isolated from the roots of Lysidice rhodostegia. Their structures were elucidated by extensive analysis of spectroscopic data (IR, UV, HR-ESI-MS, 1D and 2D NMR), ECD calculations and acid hydrolysis. Compounds 1-16 were evaluated for their antioxidant activities using DPPH radical-scavenging assay. Especially, compounds 9 and 10 exhibited stronger antioxidant effects than the positive control (vitamin E), with IC50 values of 9.57 ± 1.30 and 13.60 ± 1.47 µM, respectively.
Asunto(s)
Antioxidantes/farmacología , Fabaceae/química , Glicósidos/farmacología , Polifenoles/farmacología , Estilbenos/farmacología , Antioxidantes/aislamiento & purificación , China , Glicósidos/aislamiento & purificación , Estructura Molecular , Fitoquímicos/aislamiento & purificación , Fitoquímicos/farmacología , Raíces de Plantas/química , Polifenoles/aislamiento & purificación , Estilbenos/aislamiento & purificaciónRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Different orchids are important in traditional medicine, and species belonging to the genus Bletilla are important. Bletilla species have been used for thousands of years in Traditional Chinese Medicine (TCM) for the treatment of several health disorders, such as gastrointestinal disorders, peptic ulcer, lung disorders, and traumatic bleeding etc. AIM OF THIS REVIEW: This review aims to provide a systematic overview and objective analysis of Bletilla species and to find the probable relationship between their traditional use, chemical constituents, and pharmacological activities, while assessing their therapeutic potential in treatment of different human diseases. MATERIALS AND METHODS: Relevant literatures on Bletilla species have been collected using the keywords "Bletilla", "phytochemistry", and "pharmacology" in scientific databases, such as "PubMed", "Scifinder", "The Plant List", "Elsevier", "China Knowledge Resource Integrated databases (CNKI)", "Google Scholar", "Baidu Scholar", and other literature sources, etc. RESULTS: This review indicates the isolation and identification of over 261 compounds from this genus, till December 2020. These chemical isolates belong to the stilbenes (bibenzyls and phenanthrenes), flavonoids, triterpenoids, steroids, simple phenolics, and glucosyloxybenzyl 2-isobutylmalates classes of compounds. These compounds have been reported to be characteristically distributed in Bletilla striata (Thunb.) Rchb. f. (BS), Bletilla ochracea Schltr. (BO), and Bletilla formosana (Hayata) Schltr. (BF). The crude extracts and pure compounds derived from the three Bletilla species have reportedly exhibited a wide spectrum of in vitro and in vivo pharmacological effects, such as hemostatic, anti-inflammatory, anti-tumor, and anti-microbial activities. As a Traditional Chinese Medicine (TCM), Bletilla species or preparations containing Bletilla species have been used for the treatment of epistaxis, gastrointestinal bleeding, cough and hemoptysis, gastric and duodenal ulcer, and traumatic injuries. Thus, Bletilla species have proven potential both in traditional uses and scientific studies. CONCLUSIONS: Pharmacological studies have validated the use of Bletilla species in the traditional medicine, especially hemorrhagic diseases. Polysaccharides and stilbenes are the major bioactive chemical constituents of Bletilla genus according to the literatures. However, the mechanism of action of these molecules is yet to be studied. In addition, a detailed comparative analysis of the phytochemistry and biological activities of the three Bletilla species (BS, BO and BF) is highly recommended for understanding their ethnopharmacological uses and applications in clinics. Clinical toxicity tests on BS have been found to be negative, but it can't be used with Aconitum carmichaeli in traditional uses. Furthermore, not many reports are present in the literature regarding the conservation of Bletilla species.
Asunto(s)
Medicamentos Herbarios Chinos/farmacología , Orchidaceae/química , Animales , Medicamentos Herbarios Chinos/efectos adversos , Medicamentos Herbarios Chinos/química , Etnofarmacología , Humanos , Medicina Tradicional China , Fitoquímicos/química , Fitoquímicos/aislamiento & purificación , Fitoquímicos/farmacología , Polisacáridos/aislamiento & purificación , Polisacáridos/farmacología , Estilbenos/aislamiento & purificación , Estilbenos/farmacologíaRESUMEN
Cyperaceae is a cosmopolitan plant family with approx. 5000 species distributed worldwide. Several members of this family are used in traditional medicines for the treatment of different diseases. In the last few decades, constituents with great chemical diversity were isolated from sedges, and a wide range of biological activities were detected either for crude extracts or for pure compounds. Among the isolated compounds, phenolic derivatives are the most important, especially stilbenoids, and flavonoids. To date, more than 60 stilbenoids were isolated from 28 Cyperaceae species. Pharmacological investigation of Cyperaceae stilbenoids revealed that several compounds possess promising activities; mainly antiproliferative, antibacterial, antioxidant and anthelmintic effects. Isolation, synthesis and pharmacological investigation of stilbenes are increasing constantly. As Cyperaceae species are very good sources of a wide variety of stilbenes, and several of them occur in large amount worldwide, they are worthy for phytochemical and pharmacological investigations. Moreover, stilbenes are important from chemotaxonomical point of view, and they play a key role in plant defense mechanisms as well. This review summarizes the stilbenoids isolated from sedges, and their biological activities.
Asunto(s)
Cyperaceae/química , Estilbenos/química , Estilbenos/farmacología , Salud , Humanos , Especificidad de la Especie , Estilbenos/aislamiento & purificaciónRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: The roots of Caragana stenophylla have been used as folk medicine due to the functions of activating blood, diuresis, analgesic and tonicity, especially in treating rheumatoid arthritis and hypertension. However, the anti-rheumatoid arthritis mechanisms and bioactive ingredients have not previously been fully investigated. AIM OF THE STUDY: The aim of this study was to assess the anti-rheumatoid arthritis effects of the roots of Caragana stenophylla ethanol extract (EC), elucidate its mechanism of action and identify its active substances. MATERIALS AND METHODS: Anti-rheumatoid arthritis activity of EC was assessed using type II-collagen induced arthritis in rats. Arthritis severity was evaluated by foot paw volume, arthritis index, joint swelling degree and histopathology. The serum inflammatory cytokines and matrix metalloproteinases (MMPs) were also detected by immunohistochemical analysis. In addition, the protein expression of IκB, p-IκB, iNOS and COX-2 was analyzed by western blot. RAW 264.7 macrophage cells were employed to assess the anti-inflammatory effects of fractions and compounds in vitro. UPLC-Q-TOF-MS was adopted to appraise the ingredients of the active fraction of the roots of C. stenophylla. Furthermore, various chromatographic techniques and spectroscopic methods were used for isolation and structure elucidation of compounds. RESULTS: The results showed that EC could reduce type II collagen-induced rheumatoid arthritis model arthritic score and histopathology markedly at dose of 240 mg/kg. Besides, EC could suppress the levels of pro-inflammatory cytokines (IL-1ß, IL-6, IL-8, IL-17, and TNF-α) and matrix metalloproteinases (MMP-3, MMP-9), and the expression levels of COX-2, p-IκB and iNOS also were declined. While, the levels of IL-10 and IκB were increased. The ethyl acetate fraction exhibited potent inhibitory effects against nitric oxide production in RAW 264.7 macrophage cells. Eleven main components including 1 flavonoid and 10 oligostilbenes from active fraction were isolated by mass directed chromatographic techniques. Their structures were determined on the basis of various spectroscopic methods and by comparison with the published NMR data. CONCLUSION: The roots of C. stenophylla attenuated arthritis severity, restored serum cytokine imbalances by regulating NF-κB signaling pathway in type II collagen-induced rheumatoid arthritis model. Oligostilbenes were essential ingredients in ethyl acetate extract of C. stenophylla roots. Stilbenes and flavonoids should be responsible for its anti-rheumatoid arthritis activities.
Asunto(s)
Artritis Experimental/tratamiento farmacológico , Artritis Reumatoide/tratamiento farmacológico , Caragana/química , Extractos Vegetales/farmacología , Estilbenos/farmacología , Animales , Antiinflamatorios/química , Antiinflamatorios/aislamiento & purificación , Antiinflamatorios/farmacología , Antirreumáticos/química , Antirreumáticos/aislamiento & purificación , Antirreumáticos/farmacología , Citocinas/sangre , Femenino , Masculino , Ratones , Extractos Vegetales/química , Raíces de Plantas , Células RAW 264.7 , Ratas , Ratas Sprague-Dawley , Estilbenos/química , Estilbenos/aislamiento & purificaciónRESUMEN
Polyphenolic enriched extracts from two species of Cyperus, Cyperus glomeratus and Cyperus thunbergii, possess mammalian arginase inhibitory capacities, with the percentage inhibition ranging from 80% to 95% at 100 µg/mL and 40% to 64% at 10 µg/mL. Phytochemical investigation of these species led to the isolation and identification of two new natural stilbene oligomers named thunbergin A-B (1-2), together with three other stilbenes, trans-resveratrol (3), trans-scirpusin A (4), trans-cyperusphenol A (6), and two flavonoids, aureusidin (5) and luteolin (7), which were isolated for the first time from C.thunbergii and C. glomeratus. Structures were established on the basis of the spectroscopic data from MS and NMR experiments. The arginase inhibitory activity of compounds 1-7 was evaluated through an in vitro arginase inhibitory assay using purified liver bovine arginase. As a result, five compounds (1, 4-7) showed significant inhibition of arginase, with IC50 values between 17.6 and 60.6 µM, in the range of those of the natural arginase inhibitor piceatannol (12.6 µM). In addition, methanolic extract from Cyperus thunbergii exhibited an endothelium and NO-dependent vasorelaxant effect on thoracic aortic rings from rats and improved endothelial dysfunction in an adjuvant-induced arthritis rat model.
Asunto(s)
Arginasa/antagonistas & inhibidores , Cyperus/química , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacología , Animales , Aorta Torácica/efectos de los fármacos , Artritis Experimental/tratamiento farmacológico , Artritis Experimental/fisiopatología , Benzofuranos/química , Benzofuranos/aislamiento & purificación , Benzofuranos/farmacología , Calamus , Bovinos , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/fisiopatología , Inhibidores Enzimáticos/aislamiento & purificación , Flavonoides/química , Flavonoides/aislamiento & purificación , Flavonoides/farmacología , Técnicas In Vitro , Espectroscopía de Resonancia Magnética , Masculino , Metanol , Estructura Molecular , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/farmacología , Ratas , Resveratrol/química , Resveratrol/aislamiento & purificación , Resveratrol/farmacología , Estilbenos/química , Estilbenos/aislamiento & purificación , Estilbenos/farmacología , Vasodilatadores/química , Vasodilatadores/aislamiento & purificación , Vasodilatadores/farmacologíaRESUMEN
BACKGROUND: We had reported that cajanolactone A (CLA) from Cajanus cajan dose-dependently inhibited ovariectomy-induced obesity and liver steatosis in mice, showing potential to prevent postmenopausal obesity and fatty liver. In this study, the role of CLA in the regulation of energy and lipid homeostasis was investigated. METHODS: Ovariectomized mice treated with CLA or vehicle for 12 weeks were performed a 48 h monitoring for energy metabolism and food uptake. After that, hypothalami, perigonadal (pWATs), inguinal (iWATs) and brown (BATs) adipose tissues, livers, sera, and fecal and cecal contents were collected and analyzed. FINDINGS: In CLA-treated mice, we observed reduced food uptake; increased energy expenditure; inhibited expression of orexigenic genes (ORX, ORXR2, pMCH and Gal) in the hypothalami, of lipogenic genes (CD36, SREBP-1c, ChREBP, PPARγ) in the livers, and of lipid storage proteins in the WATs (FSP27, MEST and caveolin-1) and livers (FSP27, Plin2 and Plin5); stimulated expression of metabolism-related proteins (pATGL and Echs1) in the adipose tissues and of thermogenic protein (UCP1) in the inguinal WATs; increased BAT content; increased mitochondria in the pWATs and livers; inhibited angiogenesis in the pWATs; and altered gut microbiome diversity with an increased abundance of Bacteroides. INTERPRETATION: CLA prevents ovariectomy-induced obesity and liver steatosis via regulating energy intake and lipid synthesis/storage, promoting UCP1-dependent heat production, and protecting the mitochondrial function of hepatocytes and adipocytes. The improved gut microecology and inhibited angiogenesis may also contribute to the anti-obese activity of CLA.
Asunto(s)
Cajanus , Ingestión de Energía/efectos de los fármacos , Metabolismo Energético/efectos de los fármacos , Lipogénesis/efectos de los fármacos , Estilbenos/farmacología , Tejido Adiposo Pardo/efectos de los fármacos , Tejido Adiposo Pardo/metabolismo , Tejido Adiposo Blanco/efectos de los fármacos , Tejido Adiposo Blanco/metabolismo , Animales , Ingestión de Energía/fisiología , Metabolismo Energético/fisiología , Hígado Graso/tratamiento farmacológico , Hígado Graso/metabolismo , Femenino , Lipogénesis/fisiología , Ratones , Ratones Endogámicos C57BL , Ovariectomía/efectos adversos , Ovariectomía/tendencias , Estilbenos/aislamiento & purificación , Estilbenos/uso terapéuticoRESUMEN
Stilbenes or stilbenoids, major polyphenolic compounds of the bark of Norway spruce (Picea abies L. Karst), have potential future applications as drugs, preservatives and other functional ingredients due to their antioxidative, antibacterial and antifungal properties. Stilbenes are photosensitive and UV and fluorescent light induce trans to cis isomerisation via intramolecular cyclization. So far, the characterizations of possible new compounds derived from trans-stilbenes under UV light exposure have been mainly tentative based only on UV or MS spectra without utilizing more detailed structural spectroscopy techniques such as NMR. The objective of this work was to study the stability of biologically interesting and readily available stilbenes such as astringin and isorhapontin and their aglucones piceatannol and isorhapontigenin, which have not been studied previously. The effects of fluorescent and UV light and storage on the stability of trans stilbenes were assessed and the identification and characterisation of new compounds formed during our experiments were carried out by chromatographic (HPLC, GC) and spectroscopic techniques (UV, MS, NMR). The stilbenes undergo a trans to cis isomerisation under extended UV irradiation by intramolecular cyclisation (by the formation of a new C-C bond and the loss of two hydrogens) to phenanthrene structures. The characterised compounds are novel and not described previously.
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Luz , Picea/química , Corteza de la Planta/química , Raíces de Plantas/química , Estilbenos/química , Estilbenos/aislamiento & purificación , Fluorescencia , Cromatografía de Gases y Espectrometría de Masas , Isomerismo , Soluciones , Rayos UltravioletaRESUMEN
Sophora davidii (Franch.) Skeels is a multi-purpose traditional medicine that has long been used for the treatment of various diseases. To discover the potential bioactive composition of S. davidii, a chemical investigation was thus performed. In this research, two new stilbene oligomers, Davidiol E-F (1-2), one new 4-aryl-substituted isoflavan Davidinin A (3), and one new 2-arylbenzofuran dimer, Shandougenine C (4), as well as six known compounds (5-10) were obtained from the ethyl acetate fraction of Sophora davidii (Franch.) Skeels. The structures of new compounds were established by extensive 1D and 2D nuclear magnetic resonance (NMR) spectra with mass spectroscopy data. The absolute configuration of 1-3 was assigned by comparing its experimental and calculated electronic circular dichroism (ECD) spectra. Compounds 1-10 promoted glucose transporter 4 (GLUT-4) translocations by the range of 1.28-2.60 folds, respectively. Compound 9 showed the most potent glucose transporter 4 translocations with 1.60 fold enhancement. The result attained in this study indicated that the separation and characterization of these compounds plays an important role in the research and development of new anti-diabetic drugs and pharmaceutical industry.