RESUMEN
The present study is the first investigation of the inhibitory effect of Rhaponticum carthamoides transformed roots (TR) extract on the proliferation of grade II and III human glioma cells. TR extract showed the cytotoxic effect and inhibited the colony formation of both glioma cell lines in dose-dependent manner. The root extract induced apoptosis by increasing of the reactive oxygen species (about threefold compared to the control cells) leading to a disruption of mitochondrial membrane potential. Additionally, the mRNA levels of the apoptotic factors such as Bax, Tp53, caspase-3, and caspase-9 were observed to increase. These results indicate that the TR extract possesses anticancer activity by inhibiting glioma cell proliferation and inducing apoptotic cell death, and may be used as a promising anticancer agent.
Asunto(s)
Neoplasias Encefálicas/patología , Caspasa 3/metabolismo , Caspasa 9/metabolismo , Glioma/patología , Leuzea/química , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Extractos Vegetales/farmacología , Raíces de Plantas/química , Especies Reactivas de Oxígeno/metabolismo , Antineoplásicos Fitogénicos/farmacología , Neoplasias Encefálicas/enzimología , Neoplasias Encefálicas/metabolismo , Caspasa 3/genética , Caspasa 9/genética , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Activación Enzimática , Glioma/enzimología , Glioma/metabolismo , Humanos , Leuzea/crecimiento & desarrollo , Leuzea/metabolismo , Persona de Mediana Edad , Raíces de Plantas/crecimiento & desarrollo , Raíces de Plantas/metabolismo , Proteína p53 Supresora de Tumor/efectos de los fármacos , Proteína X Asociada a bcl-2/genéticaRESUMEN
The increasing importance of multi-resistant strains and microbial biofilms in the development of chronic infections has driven the search for more effective alternative therapy including plant-origin preparations. The present study evaluates the broadly-defined antimicrobial activity of two abietane diterpenoids isolated from Salvia austriaca transformed roots: taxodone and 15-deoxy-fuerstione. The direct biostatic/biocidal effect of these phytocompounds and their influence on Staphylococcus aureus and Candida albicans virulence factors/mechanisms (adhesion, biofilm formation, agglutination in human plasma, survival in the blood, germ tube and mycelium formation) were tested using in vitro assays. Both phytocompounds significantly inhibited microbial adhesion and biofilm formation when used at ½ and » MIC. Additionally, taxodone was able to limit staphylococcal survival in human blood, as well as C. albicans germ tube formation and hyphal growth. The tested diterpenoids express significant anti-biofilm activity against both staphylococci and yeast, and adversely affect their virulence factors/mechanisms, which are relevant in the course of the infection in vivo. Therefore, they demonstrate considerable biomedical potential as complements for classic therapy with antibiotics.
Asunto(s)
Abietanos/farmacología , Antiinfecciosos/farmacología , Candida albicans/efectos de los fármacos , Fitoquímicos/farmacología , Salvia/química , Staphylococcus aureus/efectos de los fármacos , Factores de Virulencia/antagonistas & inhibidores , Abietanos/aislamiento & purificación , Antiinfecciosos/aislamiento & purificación , Adhesión Bacteriana/efectos de los fármacos , Biopelículas/efectos de los fármacos , Candida albicans/fisiología , Hifa/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Viabilidad Microbiana/efectos de los fármacos , Fitoquímicos/aislamiento & purificación , Staphylococcus aureus/fisiologíaRESUMEN
Leonurus sibiricus L. is a traditional medicinal plant which occurs in southern Siberia, China, Korea, Japan, and Vietnam. The plant shows several pharmacological effects, but the most interesting is its anti-cancer activity. The aim of our study was to examine the induction of apoptosis in malignant glioma cells, the most aggressive primary brain tumors of the central nervous system, following treatment with transformed root (TR) or non-transformed root (NR) L. sibiricus extracts. Both the NR and TR extracts were found to have cytotoxic activity in the glioma primary cells. The human glioblastoma cell lines obtained from patients were confirmed to be tumorogenic by the following three markers: D10S1709, D10S1172, and D22S283. HPLC and MS analysis revealed the presence of polyphenolic compounds (chlorogenic acid, ferulic acid, caffeic acid, p-coumaric acid, ellagic acid, and verbascoside) in both sets of root extracts. In summary, our findings demonstrate that treatment of the glioma cells with NR and TR extracts resulted (a) in significant cell growth inhibition, (b) S- and G2/M-phase cell cycle arrest, and (c) apoptosis in a dose-dependent fashion by changing Bax/Bcl-2 ratio (about 4-fold increase) and p53 (5-fold increase) activation. These findings indicate that NR and TR extracts exhibit anti-cancer activity through the regulation of genes involved in apoptosis. This is the first report to demonstrate the cytotoxic effect of polyphenolic extracts from L. sibiricus roots against glioma cells, but further studies are required to understand the complete mechanism of its apoptosic activity.
Asunto(s)
Apoptosis/efectos de los fármacos , Glioma/tratamiento farmacológico , Leonurus/química , Raíces de Plantas/química , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Proteína X Asociada a bcl-2/metabolismo , Antineoplásicos/química , Antineoplásicos/farmacología , Biomarcadores de Tumor/metabolismo , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/metabolismo , Carcinogénesis/efectos de los fármacos , Puntos de Control del Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Glioma/metabolismo , Humanos , Persona de Mediana Edad , Extractos Vegetales/farmacología , Plantas Medicinales/química , Polifenoles/química , Polifenoles/farmacologíaRESUMEN
Taxodione, an abietane diterpenoid, was isolated from Salvia austriaca transformed roots grown in in vitro conditions. The compound is known to have antibacterial, cytotoxic and anti-tumour properties. This study evaluates the ability of pure taxodione and extracts obtained from the S. austriaca hairy roots and roots from field-grown plants to inhibit human acetylcholinesterase and butyrylcholinesterase. Both extracts were found to have similar actions against acetylcholinesterase. The IC50 for extracts from transformed and untransformed roots were 142.5 and 139.5 µg ml(-1), respectively. The highest activity towards human acetylcholinesterase was demonstrated by taxodione (IC50 = 54.84 µg ml(-1)). With respect to BChE inhibition, the root extracts demonstrated stronger activity (IC50 = 23.6 µg ml(-1): field-grown plants and 41.6 µg ml(-1): transformed roots) than taxodione (IC50 = 195.9 µg ml(-1)). Taxodione showed significant cytotoxicity against A549 cell line (IC50 = 9.1 µg ml(-1)), whereas the activities for the extracts from S. austriaca roots of field-grown plants (IC50 = 75.7 µg ml(-1)) and hairy roots (IC50 = 86.2 µg ml(-1)) were lower. Computer modelling suggests that taxodione should not demonstrate cardiotoxic or genotoxic activity. It also indicates that taxodione should demonstrate very rapid transport from the body with very good blood-brain barrier penetration, but with no cumulative effect on the human body. The obtained results indicate that taxodione is a safe compound and may be used for further investigations in pharmacological activities.
Asunto(s)
Inhibidores de la Colinesterasa/farmacología , Diterpenos/farmacología , Extractos Vegetales/farmacología , Salvia/química , Acetilcolinesterasa/metabolismo , Barrera Hematoencefálica/efectos de los fármacos , Butirilcolinesterasa/metabolismo , Línea Celular , Inhibidores de la Colinesterasa/aislamiento & purificación , Diterpenos/aislamiento & purificación , Humanos , Modelos Químicos , Raíces de Plantas/químicaRESUMEN
Methanolic extracts from the aerial parts and roots of two Scutellaria species, S. alpina and S. altissima, and five polyphenols from these plants demonstrated a significant ability to inhibit the formation of advanced glycation end-products (AGE) in vitro. S. alpina, which is richer in polyphenolic compounds, had strong antiglycation properties. These extracts demonstrated also high activity in the FRAP (ferric-reducing antioxidant power), antiradical (DPPH) and lipid peroxidation inhibition assays. Among the pure compounds, baicalin was the strongest glycation inhibitor (90.4% inhibition at 100 µg/mL), followed by luteolin (85.4%). Two other flavone glycosides had about half of this activity. Verbascoside was similar to the reference drug aminoguanidine (71.2% and 75.9%, respectively). The strong correlation observed between AGE inhibition and total flavonoid content indicated that flavonoids contribute significantly to antiglycation properties. A positive correlation was also observed between antiglycative and antioxidant activities. The studied skullcap species can be considered as a potential source of therapeutic agents for hyperglycemia-related disorders.
Asunto(s)
Productos Finales de Glicación Avanzada/antagonistas & inhibidores , Hiperglucemia/tratamiento farmacológico , Extractos Vegetales/química , Polifenoles/química , Animales , Antioxidantes/química , Antioxidantes/uso terapéutico , Bovinos , Flavonoides/química , Flavonoides/farmacología , Peroxidación de Lípido/efectos de los fármacos , Extractos Vegetales/farmacología , Raíces de Plantas/química , Polifenoles/farmacología , Scutellaria/química , Albúmina Sérica Bovina/químicaRESUMEN
Amoebae from the genus Acanthamoeba are known agents leading to various diseases such as granulomatous amoebic encephalitis (GAE), a chronic progressive disease of the central nervous system, amoebic keratitis (AK), chronic eye infection, amoebic pneumitis (AP), chronic lung infection, and skin infections. It is known that various synthetic anti-Acanthamoeba substances are ineffective. Therefore, other substances, e.g., natural plant compounds, are the focus of biological investigations regarding anti-parasite activity. In this work, the ability of four abietane diterpenoids (ferruginol, salvipisone, aethiopinone, and 1-oxo-aethiopinone) to inhibit Acanthamoeba growth is reported. All investigated compounds were active against Acanthamoeba growing in vitro. Among them, ferruginol demonstrated the highest activity against Acanthamoeba. This compound inhibited Acanthamoeba growth by about 72% in a 3-day exposure period (IC50 17.45 µM), while aethiopinone and 1-oxo-aethiopinone demonstrated this activity at the level of 55-56%. Salvipisone reduced the growth of Acanthamoeba in vitro culture by 39%. For this compound, the value of IC50 was 701.94 µM after 72 h of exposure.
Asunto(s)
Abietanos/farmacología , Acanthamoeba/efectos de los fármacos , Amebicidas/farmacología , Diterpenos/farmacología , Naftoquinonas/farmacología , Salvia/química , Abietanos/aislamiento & purificación , Acanthamoeba/crecimiento & desarrollo , Amebicidas/aislamiento & purificación , Diterpenos/aislamiento & purificación , Naftoquinonas/aislamiento & purificación , Extractos Vegetales/química , Raíces de Plantas/químicaRESUMEN
Antioxidant properties and total phenolic and flavonoid contents were evaluated in methanolic extracts of shoots from Ballota nigra plants initiated in vitro (from nodal explants) and in vivo (from seeds). The plants were grown in greenhouse and in the field, and were analyzed at the vegetative and flowering stages. The shoot extract of wild-grown plants of B. nigra was also investigated. The results indicate that antioxidant potential of the B. nigra extracts seems to be due to their scavenging of free radicals (DPPH assay) and metal reducing (FRAP test), while they were less effective at the prevention of linoleic acid peroxidation (LPO test). The extracts from shoots of in vitro derived plants were found to exhibit the greatest antioxidant properties. The extracts were also characterized by the highest content of phenolic compounds and their level was affected by plant developmental stage. The extracts of shoots collected at the flowering period exhibited higher amounts of phenolics and flavonoids than in the extracts of immature plants. A close correlation between the total phenolic content and flavonoid content and antioxidant activity using the DPPH and FRAP assays was obtained. The results of the present study suggest the use in vitro-derived plants of B. nigra instead of using wild plants for pharmaceutical purposes.
Asunto(s)
Antioxidantes/farmacología , Ballota , Extractos Vegetales/farmacología , Ballota/química , Flavonoides/análisis , Fenoles/análisis , Técnicas de Cultivo de TejidosRESUMEN
Compounds with antioxidant activity may protect different elements of blood from damaging effects of oxidative stress. The present in vitro study was designed to examine the antioxidant activity of methanolic extracts from leaves and roots of R. glutinosa plants against damages induced by oxidative stress. Oxidative stress was stimulated in human plasma and human blood platelet samples by the strong biological oxidant--hydrogen peroxide (H2O2) or H2O2/Fe (the donor of hydroxyl radicals). In experimental trials, the level of biomarker of lipid peroxidation--TBARS was significantly decreased by the action of methanolic extracts from R. glutinosa leaves. Therefore, it seems that the methanolic extract from leaves of the plants may be a new source of bioactive antioxidant natural compounds. It may be also an active pharmacological agent or a food supplement for healthy subjects and for people with different diseases (cardiovascular diseases and cancer) induced by oxidative stress.
Asunto(s)
Antioxidantes/farmacología , Extractos Vegetales/farmacología , Rehmannia , Cromatografía Líquida de Alta Presión , Humanos , Masculino , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/análisis , Hojas de la Planta , Rehmannia/química , Sustancias Reactivas al Ácido Tiobarbitúrico/análisisRESUMEN
The essential oils obtained by hydrodistillation of dried aerial parts of Salvia sclarea L. plants, regenerated in vitro and reproduced from seeds, were analyzed by GC and GC-MS. The oils from in vitro and in vivo plants were compared in respect to their chemical composition as well as antimicrobial and cytotoxic activities. The chemical profiles of both oils were very similar, although the yield of essential oil from in vitro plants was lower (0.1%, v/w) than the oil yield isolated from in vivo S. sclarea plants (0.2%, v/w). Both oils showed antimicrobial and cytotoxic activity. The oil from in vitro regenerated plants of S. sclarea exhibited stronger cytotoxic action against NALM-6 cell lines in comparison with the essential oil from in vivo plants.
Asunto(s)
Aceites Volátiles/química , Aceites de Plantas/química , Regeneración/fisiología , Salvia/química , Salvia/fisiología , Línea Celular Tumoral/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Humanos , Pruebas de Sensibilidad Microbiana , Aceites Volátiles/farmacología , Aceites de Plantas/farmacología , Salvia/anatomía & histologíaRESUMEN
BACKGROUND: It is widely known that reactive oxygen species (ROS) can cause oxidative damage in cells and have been linked to the pathogenesis of oxidative diseases, such as atherosclerosis, ischemia, neurodegenerative disease, diabetes, or cancer. Recently, much attention has been focused on preventive strategies for oxidative stress and related diseases. Plants represent a source of bioactive compounds whose antioxidant activity may be useful in protecting against pro-oxidative reactions. OBJECTIVES: The study determines the in vitro biological activity of the ethanolic extracts from the shoots and roots of Scutellaria species (S. altissima and S. alpina) in selected blood cells (blood platelets and lymphocytes). MATERIAL AND METHODS: Platelet activity, both resting and after thrombin stimulation, was used to indicate the ability of the plant extracts to inhibit the production of superoxide anion radicals (O2 â¢-) and platelet lipid peroxidation. The generation of superoxide anion radicals was measured by cytochrome c reduction. Lipid peroxidation in blood platelets was measured by the level of thiobarbituric acid reactive substances (TBARS). The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assay was used to determine the protective effect of Scutellaria extracts on lymphocyte cells against oxidative damage induced by hydroxyl radicals. RESULTS: Extracts (5-50 µg/mL) containing phenolic compounds from both Scutellaria species distinctly reduced nonenzymatic lipid peroxidation and arachidonic acid metabolism by blood platelets in vitro. When given at the tested concentration, the extracts reduced the generation of O2 â¢- in resting blood platelets and platelets activated by thrombin in vitro. All Scutellaria extracts (10 µg/mL) containing phenolic compounds also protected human lymphocytes against oxidative stress induced by hydrogen peroxide (H2O2). CONCLUSIONS: The present study suggests that the natural extracts from S. altissima and S. alpina have antioxidant properties and, therefore, may be beneficial in the prevention of diseases in which blood platelets and lymphocytes are involved, i.e., cancer or inflammatory and infective diseases.
Asunto(s)
Antioxidantes/farmacología , Plaquetas/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/farmacología , Scutellaria/química , Antioxidantes/análisis , Plaquetas/metabolismo , Humanos , Peróxido de Hidrógeno/farmacología , Peroxidación de Lípido/efectos de los fármacos , Estrés Oxidativo/fisiología , Extractos Vegetales/análisis , Raíces de Plantas/química , Brotes de la Planta/química , Scutellaria baicalensisRESUMEN
Growth and diterpenoid accumulation (salvipisone, ferruginol, aethiopinone and 1-oxoaethiopinone) during the growth cycle of a Salvia sclarea hairy root culture are described. The roots transformed by Agrobacterium rhizogenes (LBA 9402) were cultured in half-strength B5 liquid medium supplemented with 30 g L(-1) sucrose under light (16 h/8 h light/dark). A culture period of 30 days was optimal for both biomass and diterpenoid production. The total content of four diterpenoids in the hairy roots [(27.3 +/- 0.6) mg g(-1) dry weight] was higher than that of roots of field-grown S. sclarea plants [(3.15 +/- 0.15) mg g(-1) dry weight]. In transformed roots, aethiopinone was the main diterpenoid, whereas the principal diterpenoid of natural roots was salvipisone.
Asunto(s)
Diterpenos/metabolismo , Raíces de Plantas/metabolismo , Salvia/metabolismo , Técnicas de Cultivo , Raíces de Plantas/crecimiento & desarrollo , Raíces de Plantas/microbiología , Rhizobium , Salvia/microbiologíaRESUMEN
The complete exploration of the regulation of gene expression remains one of the top-priority goals for researchers. As the regulation is mainly controlled at the level of transcription by promoters, study on promoters and findings are of great importance. This review summarizes forty selected databases that centralize experimental and theoretical knowledge regarding the organization of promoters, interacting transcription factors (TFs) and microRNAs (miRNAs) in many eukaryotic and prokaryotic species. The presented databases offer researchers valuable support in elucidating the regulation of gene transcription.
Asunto(s)
Eucariontes/genética , Células Eucariotas/fisiología , Células Procariotas/fisiología , Regiones Promotoras Genéticas/genética , Transcripción Genética/genética , Animales , Bases de Datos de Ácidos Nucleicos , Humanos , MicroARNs/genética , Factores de Transcripción/genéticaRESUMEN
This study examines the production of five phenolic acids (chlorogenic acid, neochlorogenic acid, ferulic acid, caffeic acid and p-coumaric acid) following over-expression of AtPAP1 transcription factor by four transgenic root clones of Leonurus sibiricus after Agrobacterium rhizogenes transformation. The AtPAP1 expression level was estimated by quantitative real-time PCR. High levels of phenolic acids were found in the transgenic roots of L. sibiricus and were determined by high-performance liquid chromatography-mass spectrometry analysis. Additionally, transgenic roots showed antimicrobial potential and cytotoxic activity on glioma cells in IV grade. Our results suggest that L. sibiricus transformed roots with AtPAP1 gene over-expression may represent a potential source of phenolic acids.
Asunto(s)
Antiinfecciosos/farmacología , Antineoplásicos Fitogénicos/farmacología , Proteínas de Arabidopsis/genética , Leonurus/genética , Leonurus/metabolismo , Factores de Transcripción/genética , Agrobacterium/genética , Proteínas de Arabidopsis/metabolismo , Ácidos Cafeicos/metabolismo , Línea Celular Tumoral , Ácido Clorogénico/análogos & derivados , Ácido Clorogénico/metabolismo , Ácidos Cumáricos/metabolismo , Regulación de la Expresión Génica de las Plantas , Glioma/tratamiento farmacológico , Humanos , Ingeniería Metabólica/métodos , Raíces de Plantas/genética , Raíces de Plantas/metabolismo , Plantas Modificadas Genéticamente , Propionatos/metabolismo , Ácido Quínico/análogos & derivados , Ácido Quínico/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , Factores de Transcripción/metabolismoRESUMEN
The procedure of Salvia przewalskii shoot multiplication and the ability of regenerated plants to produce essential oil is reported. The essential oil was obtained by hydrodistillation from leaves and flowering stems of field-grown plants, and their chemical composition was examined by GC, GC-MS and 1H NMR. The differences in yield as well as qualitative and quantitative composition between the oils isolated from in vitro and in vivo plants were observed. S. przewalskii essential oil was tested for its antimicrobial and cytotoxic properties. It was found that cytotoxicity against human leukemia HL-60 cells and antimicrobial activity (especially, against Staphylococcus aureus and S. epidermidis strains) of oils isolated from in vitro plants were higher than those for oils from in vivo S. przewalskii plants.
Asunto(s)
Aceites Volátiles/aislamiento & purificación , Aceites Volátiles/farmacología , Aceites de Plantas/aislamiento & purificación , Aceites de Plantas/farmacología , Salvia/química , Antineoplásicos/aislamiento & purificación , Antineoplásicos/farmacología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Cromatografía de Gases , Flores/química , Cromatografía de Gases y Espectrometría de Masas , Células HL-60 , Humanos , Espectroscopía de Resonancia Magnética , Pruebas de Sensibilidad Microbiana , Hojas de la Planta/química , Tallos de la Planta/químicaRESUMEN
Essential oils obtained from the NR (normal roots) and HR (hairy roots) of the medicinal plant Leonurus sibiricus root were used in this study. The essential oil compositions were detected by GC-MS. Eighty-five components were identified in total. Seventy components were identified for NR essential oil. The major constituents in NR essential oil were ß-selinene (9.9%), selina-4,7-diene (9.7%), (E)-ß-caryophyllene (7.3%),myli-4(15)-ene (6.4%), and guaia-1(10),11-diene (5.9%). Sixty-seven components were identified in HR essential oil, the main constituents being (E)-ß-caryophyllene (22.6%), and germacrene D (19.8%). The essential oils were tested for cytotoxic effect, antimicrobial, anti-inflammatory, and antioxidant activities. Both essential oils showed activity against grade IV glioma cell lines (IC50 = 400 µg/mL), antimicrobial (MIC and MFC values of 2500 to 125 µg/mL), and anti-inflammatory (decreased level of IL-1ß, IL-6, TNF-α, and IFN-γ in LPS-stimulated cells).The essential oils exhibited moderate antioxidant activity in ABTS (EC50 = 98 and 88 µg/mL) assay. This is the first study to examine composition of the essential oils and their antimicrobial, antioxidant, antiproliferative, and anti-inflammatory activities. The results indicate that essential oils form L. sibiricus root may be used in future as an alternative to synthetic antimicrobial agents with potential application in the food and pharmaceutical industries.
Asunto(s)
Leonurus , Neuroglía/efectos de los fármacos , Aceites Volátiles/farmacología , Aceites de Plantas/farmacología , Antibacterianos/farmacología , Antiinflamatorios/farmacología , Antioxidantes/farmacología , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Ensayo de Inmunoadsorción Enzimática , Glioma , Humanos , Leonurus/química , Pruebas de Sensibilidad Microbiana , Aceites Volátiles/química , Aceites de Plantas/química , Raíces de Plantas/química , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
This study determines the influence of transformed root (TR) extract of Leonurus sibiricus L. on various grades (I-III) of human glioma cells derived from patients. This plant occurs in southern Asia and Siberia and is widely used as a medicinal plant with various biological activities. Chromatographic profile of TR extract have revealed the presence of various polyphenolic compounds (4-hydroxybenzoic acid, gentisic acid, vanilic acid, 1,3-dicaffeoylquinic acid, α-resorcylic acid). We found TR root extract to have antiproliferative activity on glioma cells after 24 h of treatment. TR root extract induces apoptosis on various grades (I-III) of human glioma cells by the generation of reactive oxygen species (ROS) along with concurrent loss of mitochondrial membrane potential, enhanced S and G2/M phases of the cell cycle, and altered mRNA levels of Bax, Bcl-2, p53, Cas-3, Cas-8 and Cas-9 factors involved in apoptosis. This work for the first time demonstrate that TR extract from L. sibiricus root has the potential to activate apoptosis in grade I-III human glioma cells through the intrinsic and extrinsic pathways.
Asunto(s)
Apoptosis/efectos de los fármacos , Glioma/tratamiento farmacológico , Leonurus/química , Extractos Vegetales/farmacología , Raíces de Plantas/química , Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Glioma/metabolismo , Humanos , Hidroxibenzoatos/farmacología , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Parabenos/farmacología , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Ácido Quínico/análogos & derivados , Ácido Quínico/farmacología , Especies Reactivas de Oxígeno/metabolismo , Resorcinoles/farmacología , Proteína X Asociada a bcl-2/metabolismoRESUMEN
Shoots of Salvia officinalis, a medicinally important plant, were infected with Agrobacterium rhizogenes strains ATCC 15834 and A4 which led to the induction of hairy roots in 57% and 37% of the explants, respectively. Seven lines of hairy roots were established in WP liquid medium under light and dark conditions. The transformed nature of the root lines was confirmed by polymerase chain reaction using rolB and rolC specific primers. Transformed root cultures of Salvia officinalis showed variations in biomass and rosmarinic acid production depending on the bacterial strain used for transformation and the root line analyzed. Both parameters (growth and rosmarinic acid content) of ATCC 15834-induced lines were significantly higher than the A4-induced lines. The maximum accumulation of rosmarinic acid (about 45 mg g(-1) of dry weight) was achieved by hairy root line 1 (HR-1) at the end of the culture period (45-50 days). The level was significantly higher than that found in untransformed root culture (19 mg g(-10 of dry wt).
Asunto(s)
Cinamatos/metabolismo , Cinamatos/farmacología , Raíces de Plantas/crecimiento & desarrollo , Salvia/crecimiento & desarrollo , Antifúngicos/aislamiento & purificación , Antifúngicos/farmacología , Técnicas de Cultivo de Célula , Cinamatos/aislamiento & purificación , Depsidos , Raíces de Plantas/química , Raíces de Plantas/citología , Raíces de Plantas/genética , Rhizobium/efectos de los fármacos , Salvia/química , Ácido RosmarínicoRESUMEN
Four diterpenoids, ferruginol, salvipisone, aethiopinone and 1-oxoaethiopinone, were isolated from transformed roots of Salvia sclarea. Salvipisone and aethiopinone showed relatively high cytotoxicity against HL-60 and NALM-6 leukemia cells (IC50 range 0.6-7.7 microg/ mL which is equal to 2.0-24.7 microM), whereas 1-oxoaethiopinone and ferruginol were less active in this regard. Moreover, we have found that all four diterpenoids of S. sclarea had equal cytotoxic activity against parental HL-60 and multidrug-resistant HL-60 ADR cells, what indicates that they are poor substrates for transport by multidrug resistance-associated protein (MRP1). Caspase-3 activity determinations showed that salvipisone and aethiopinone were able to induce apoptosis in a time- and concentration-dependent manner. The results obtained in this study show that S. sclarea diterpenoids aethiopinone and salvipisone may be useful in the treatment of human cancers, especially in the case of drug resistance.
Asunto(s)
Apoptosis/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Diterpenos/aislamiento & purificación , Diterpenos/toxicidad , Raíces de Plantas/química , Salvia/química , Caspasa 3 , Caspasas/efectos de los fármacos , Caspasas/metabolismo , Línea Celular Tumoral , Diterpenos/química , Doxorrubicina , Resistencia a Múltiples Medicamentos , Células HL-60 , Humanos , Cinética , Leucemia , Estructura Molecular , Brotes de la PlantaRESUMEN
Rhaponticum carthamoides has a long tradition of use in Siberian folk medicine. The roots and rhizomes of this species are used in various dietary supplements or nutraceutical preparations to increase energy level or eliminate physical weakness. This is the first report to reveal the protective and DNA repair stimulating abilities of R. carthamoides root extracts in Chinese hamster ovary (CHO) cells exposed to an oxidative agent. Both transformed root extract (TR extract) and extract of soil-grown plant roots (NR extract) may be responsible for stimulating CHO cells to repair oxidatively induced DNA damage, but CHO cells stimulated with extract from the transformed roots demonstrated significantly stronger properties than cells treated with the soil-grown plant root extract. These differences in biological activity may be attributed to the differences in the content of phenolic compounds in these root extracts. Preincubation of the CHO cells with TR and NR extracts showed an increase in gene expression and protein levels of catalase (CAT) and superoxide dismutase (SOD2). R. carthamoides may possess antioxidant properties that protect CHO cells against oxidative stress.
Asunto(s)
Antioxidantes/farmacología , Daño del ADN , Reparación del ADN/efectos de los fármacos , Leuzea/química , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/farmacología , Raíces de Plantas/química , Animales , Antioxidantes/química , Células CHO , Cricetinae , Cricetulus , Extractos Vegetales/químicaRESUMEN
Leonurus sibiricus L. has been used as a traditional and medicinal herb for many years in Asia and Europe. This species is known to have antibacterial, anti-inflammatory, and antioxidant activity and has demonstrated a reduction of intracellular reactive oxygen species. All tested extracts of L. sibiricus showed protective and DNA repair stimulating effects in Chinese hamster ovary (CHO) cells exposed to H2O2. Preincubation of the CHO cells with 0.5 mg/mL of plant extracts showed increased expression level of antioxidant genes (SOD2, CAT, and GPx). LC-MS/MS and HPLC analyses revealed the presence of nine phenolic compounds in L. sibiricus plant extracts: catechin, verbascoside, two flavonoids (quercetin and rutin), and five phenolic acids (4-hydroxybenzoic acid, chlorogenic acid, caffeic acid, p-coumaric acid, and ferulic acid). The roots and aerial parts of in vitro L. sibiricus plant extracts, which had the strongest antioxidant properties, may be responsible for stimulating CHO cells to repair oxidatively induced DNA damage, as well as protecting DNA via enhanced activation of the antioxidant genes (SOD2, CAT, and GPx) regulating intracellular antioxidant capacity. The content of phenolic compounds in in vitro raised plants was greater than the levels found in plants propagated from seeds.