RESUMEN
Annona diversifolia Safford and two acyclic terpenoids were evaluated to determine their antihyperglycemic activity as potential α-glucosidase and selective SGLT-1 inhibitiors. Ethanolic extract (EEAd), chloroformic (CHCl3Fr), ethyl acetate (EtOAcFr), aqueous residual (AcRFr), secondary 5 (Fr5) fractions, farnesal (1), and farnesol (2) were evaluated on normoglycemic and streptozocin-induced diabetic mice. EEAd, CHCl3Fr, Fr5, (1) and (2) showed antihyperglycemic activity. The potential as α-glucosidase inhibitors of products was evaluated with oral sucrose and lactose tolerance (OSTT and OLTT, respectively) and intestinal sucrose hydrolysis (ISH) tests; the potential as SGLT-1 inhibitors was evaluated using oral glucose tolerance (OGTT), intestinal glucose absorption (IGA), and urinary glucose excretion (UGE) tests. In OSTT and OLTT, all treatments showed significant activity at two and four hours. In ISH, half maximal effective concentrations (CE50) of 565, 662 and 590 µg/mL, 682 and 802 µM were calculated, respectively. In OGTT, all treatments showed significant activity at two hours. In IGA, CE50 values of 1059, 783 and 539 µg/mL, 1211 and 327 µM were calculated, respectively. In UGE Fr5, (1) and (2) showed significant reduction of the glucose excreted compared with canagliflozin. These results suggest that the antihyperglycemic activity is mediated by α-glucosidase and selective SGLT-1 inhibition.
Asunto(s)
Annona/química , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes/administración & dosificación , Transportador 1 de Sodio-Glucosa/metabolismo , Terpenos/administración & dosificación , alfa-Glucosidasas/metabolismo , Administración Oral , Animales , Glucemia/efectos de los fármacos , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/inducido químicamente , Diabetes Mellitus Tipo 2/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Inhibidores de Glicósido Hidrolasas/administración & dosificación , Inhibidores de Glicósido Hidrolasas/química , Inhibidores de Glicósido Hidrolasas/farmacología , Hipoglucemiantes/química , Hipoglucemiantes/farmacología , Masculino , Ratones , Estructura Molecular , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Ratas , Estreptozocina , Terpenos/química , Terpenos/farmacologíaRESUMEN
Galectin-3 (Gal-3) controls intercellular and cell-extracellular matrix interactions during immunological responses. In chronic inflammation, Gal-3 is associated with fibrotic events, regulates B cell differentiation and delays lupus progression. Gal-3 deficient mice (Lgals3-/-) have intense germinal center formation and atypical plasma cell generation correlated to high levels IgG, IgE, and IgA. Here, we used pristane (2,6,10,14-tetramethylpentadecane) to induce lupus-like syndrome in Lgals3-/- and Lgals3+/+ BALB/c mice. Mesentery and peritoneal cells were monitored because promptly react to pristane injected in the peritoneal cavity. For the first time, mesenteric tissues have been associated to the pathogenesis of experimental lupus-like syndrome. In Lgals3+/+ pristane-induced mice, mesentery was hallmarked by intense fibrogranulomatous reaction restricted to submesothelial regions and organized niches containing macrophages and B lymphocytes and plasma cells. In contrast, Lgals3-/- pristane-treated mice had diffuse mesenteric fibrosis affecting submesothelium and peripheral tissues, atypical M1/M2 macrophage polarization and significant DLL1+ cells expansion, suggesting possible involvement of Notch/Delta pathways in the disease. Early inflammatory reaction to pristane was characterized by significant disturbances on monocyte recruitment, macrophage differentiation and dendritic cell (DC) responses in the peritoneal cavity of pristane-induced Lgals3-/- mice. A correlative analysis showed that mesenteric damages in the absence of Gal-3 were directly associated with severe portal inflammation and hepatitis. In conclusion, it has suggested that Gal-3 orchestrates histological organization in the mesentery and prevents lupoid hepatitis in experimental lupus-like syndrome by controlling macrophage polarization, Notch signaling pathways and DC differentiation in mesenteric structures.
Asunto(s)
Galectina 3/metabolismo , Hepatitis/inmunología , Lupus Eritematoso Sistémico/inmunología , Macrófagos Peritoneales/inmunología , Mesenterio/patología , Animales , Modelos Animales de Enfermedad , Femenino , Fibrosis , Galectina 3/genética , Hepatitis/patología , Humanos , Inyecciones Intraperitoneales , Hígado/inmunología , Hígado/patología , Lupus Eritematoso Sistémico/inducido químicamente , Lupus Eritematoso Sistémico/complicaciones , Mesenterio/citología , Mesenterio/inmunología , Ratones , Ratones Noqueados , Terpenos/administración & dosificación , Terpenos/inmunologíaRESUMEN
The inflammatory and autoimmune events preceding clinical symptoms in rheumatoid arthritis (RA) and other autoimmune diseases are difficult to study in human patients. Therefore, animal models that share immunologic and clinical features with human RA, such as pristane-induced arthritis (PIA), are valuable tools for assessing the primordial events related to arthritis susceptibility. PIA-resistant HIII and susceptible LIII mice were injected i.p. with pristane, and peritoneal lavage fluid was harvested in the early (7 days) and late (35 days) preclinical phases of PIA. Chemokine and cytokine levels were measured in lavage supernatant with ELISA, peritoneal inflammatory leukocytes were immunophenotyped by flow cytometry, and gene expression was determined by qRT-PCR. Leukocyte recruitment was quantitatively and qualitatively divergent in the peritoneum of HIII and LIII mice, with an early increase of CC chemokines (CCL2/CCL3/CCL5/CCL12/CCL22) in the susceptible LIII strain. Also, cytokines such as IL-12p40, IL-23, and IL-18 were elevated in LIII mice while IL-6 was increased in HIII animals. The results show that an early peritoneal CC chemokine response is an important feature of arthritis susceptibility and defines potential biomarkers in this model.
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Artritis Experimental/inmunología , Artritis Reumatoide/inmunología , Quimiocinas CC/inmunología , Inflamación , Peritoneo/inmunología , Animales , Artritis Experimental/inducido químicamente , Biomarcadores , Citocinas/inmunología , Modelos Animales de Enfermedad , Femenino , Interleucina-6/inmunología , Masculino , Ratones , Fenotipo , Terpenos/administración & dosificaciónRESUMEN
Essential oils are natural products with a complex composition. Terpenes are the most common class of chemical compounds present in essential oils. Terpenes and the essential oils containing them are widely used and investigated by their pharmacological properties and permeation-enhancing ability. However, many terpenes and essential oils are sensitive to environmental conditions, undergoing volatilization and chemical degradation. In order to overcome the chemical instability of some isolated terpenes and essential oils, the encapsulation of these compounds in nanostructured systems (polymeric, lipidic, or molecular complexes) has been employed. In addition, nanoencapsulation can be of interest for pharmaceutical applications due to its capacity to improve the bioavailability and allow the controlled release of drugs. Topical drug administration is a convenient and non-invasive administration route for both local and systemic drug delivery. The present review focuses on describing the current status of research concerning nanostructured delivery systems containing isolated terpenes and/or essential oils designed for topical administration and on discussing the use of terpenes and essential oils either for their biological activities or as permeation enhancers in pharmaceutic formulations.
Asunto(s)
Diseño de Fármacos , Nanoestructuras/química , Aceites Volátiles/administración & dosificación , Terpenos/administración & dosificación , Administración Tópica , Animales , Sistemas de Liberación de Medicamentos , Humanos , Nanotecnología , Aceites Volátiles/química , Aceites Volátiles/aislamiento & purificación , Terpenos/química , Terpenos/aislamiento & purificaciónRESUMEN
OBJECTIVES: The human skin microbiota is mainly composed of bacteria belonging to the genera Staphylococcus, Cutibacterium, Micrococcus and Corynebacterium, but on the skin of the face and back, ca. 50% of the total microbiota is represented by the bacterium Cutibacterium acnes. The aim of this research was to evaluate the impact of C. martini EO and its major compound, geraniol, on C. acnes. METHODS: The minimum inhibitory concentration against C. acnes strains, phenotypic changes and responses of the proteome was determined. In addition, was assessed the effect of compounds in RNA-binding assay, on C. acnes-exposed keratinocytes and on the C. acnes type distribution on shoulder skin. KEY FINDINGS: The range of the MIC was 0.7 to 1.6 mg/ml for the three main C. acnes types. There were no cytotoxic effects of compounds in the absence or presence of C. acnes; after 7 days of exposure to C. martini EO, we could not detect a major shift of the C. acnes types on shoulder skin that was found to be dominated by C. acnes strains of types II and IA2. CONCLUSIONS: Our work gives novel insight into the skin microbiota-interacting properties of C. martini EO.
Asunto(s)
Cymbopogon , Queratinocitos/efectos de los fármacos , Aceites Volátiles/farmacología , Propionibacterium acnes/efectos de los fármacos , Monoterpenos Acíclicos , Relación Dosis-Respuesta a Droga , Humanos , Pruebas de Sensibilidad Microbiana , Aceites Volátiles/administración & dosificación , Piel/efectos de los fármacos , Terpenos/administración & dosificación , Terpenos/farmacologíaRESUMEN
The nanoencapsulation of botanical compounds (such as geraniol) is an important strategy that can be used to increase the stability and efficiency of these substances in integrated pest management. In this study, chitosan/gum arabic nanoparticles containing geraniol were prepared and characterized. In addition, evaluation was made of the biological activity of geraniol encapsulated in chitosan/gum arabic nanoparticles toward whitefly ( Bemisia tabaci). The optimized formulation showed a high encapsulation efficiency (>90%) and remained stable for about 120 days. The formulation protected the geraniol against degradation by UV radiation, and the in vitro release was according to a diffusion mechanism that was influenced by temperature. An attraction effect was observed for Bemisia tabaci, indicating the potential of this type of system for use in pest management, especially in trap devices.
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Agricultura/métodos , Quitosano , Goma Arábiga , Control de Insectos/métodos , Nanopartículas/química , Terpenos/administración & dosificación , Monoterpenos Acíclicos , Animales , Difusión , Estabilidad de Medicamentos , Hemípteros , Control de Insectos/instrumentación , Insecticidas/administración & dosificaciónRESUMEN
Pristane-induced arthritis (PIA) in mice is an experimental model that resembles human rheumatoid arthritis, a chronic autoimmune disease that affects joints and is characterized by synovial inflammation and articular cartilage and bone destruction. AIRmax and AIRmin mouse lines differ in their susceptibility to PIA, and linkage analysis in this model mapped arthritis severity QTLs in chromosomes 5 and 8. miRNAs are a class of small RNA molecules that have been extensively studied in the development of arthritis. We analyzed miRNA and gene expression profiles in peritoneal cells of AIRmax and AIRmin lines, in order to evaluate the genetic architecture in this model. Susceptible AIRmax mice showed higher gene (2025 vs 1043) and miRNA (240 vs 59) modulation than resistant AIRmin mice at the onset of disease symptoms. miR-132-3p/212-3p, miR-106-5p, miR-27b-3p, and miR-25-3p were among the miRNAs with the highest expression in susceptible animals, showing a negative correlation with the expression of predicted target genes (Il10, Cd69, and Sp1r1). Our study showed that global gene and miRNA expression profiles in peritoneal cells of susceptible AIRmax and resistant AIRmin lines during pristane-induced arthritis are distinct, evidencing interesting targets for further validation.
Asunto(s)
Artritis Experimental/genética , Artritis Reumatoide/genética , MicroARNs/genética , Peritoneo/fisiología , Animales , Artritis Experimental/inducido químicamente , Células Cultivadas , Susceptibilidad a Enfermedades , Femenino , Humanos , Interleucina-10/genética , Masculino , Ratones , Ratones Mutantes , Peritoneo/patología , Sitios de Carácter Cuantitativo/genética , Terpenos/administración & dosificación , TranscriptomaRESUMEN
(1S)-(-)-verbenone (VRB) is a monoterpene present in the essential oils of many plants which has shown therapeutic effect; however, its anticonvulsant activity has not yet been evaluated. The present work sought to investigate the anticonvulsant activity of VRB using pilocarpine and pentylenetetrazole-induced seizure testing; seeking also probable mechanisms of action. VRB caused no significant changes in motor coordination. Also, no significant data was observed in the pilocarpine-induced seizure tests. In the PTZ-induced seizures test, VRB showed anticonvulsant activity at doses of 200 mg/kg i.p. (733 ± 109.4 s) and 250 mg/kg i.p. (648.8 ± 124.5 s) significantly increasing the latency to onset of first seizure as compared with the vehicle group (51.8 ± 2.84 s). Pretreatment with flumazenil (FLU) did not reverse the anticonvulsive effect of VRB; however, it was able to upregulate BDNF and COX-2 genes and downregulate c-fos. The findings suggest that the anticonvulsant effects of VRB may be related to RNA expression modulations of COX-2, BDNF, and c-fos.
Asunto(s)
Anticonvulsivantes/farmacología , Convulsiones/tratamiento farmacológico , Terpenos/farmacología , Animales , Anticonvulsivantes/administración & dosificación , Monoterpenos Bicíclicos , Factor Neurotrófico Derivado del Encéfalo/genética , Ciclooxigenasa 2/genética , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Regulación hacia Abajo/efectos de los fármacos , Masculino , Ratones , Pentilenotetrazol , Pilocarpina , Proteínas Proto-Oncogénicas c-fos/genética , ARN Mensajero/metabolismo , Terpenos/administración & dosificación , Regulación hacia Arriba/efectos de los fármacosRESUMEN
AIMS: We have investigated the antihyperalgesic effects of limonene in mice that received intrathecal injection of gp120. MAIN METHODS: Male Swiss mice received gp120, IL-1ß or TNF-α intrathecally or sterile saline as a control. A mechanical sensitivity test was performed at 2 and 3h after the injection. Spinal cord and blood samples were isolated for protein quantification. KEY FINDINGS: Intrathecal administration of gp120 increased mechanical sensitivity measured with an electronic Von Frey apparatus, at 2 and 3h after the injections. Limonene administered orally prior to gp120 administration significantly decreased this mechanical sensitivity at 3h after the gp120 injection. In addition, intrathecal injection of gp120 increased IL-1ß and IL-10 in serum, and limonene prevented the ability of gp120 to increase these cytokines. Limonene also inhibited TNF-α and IL-1ß-induced mechanical hyperalgesia. Western blot assay demonstrated limonene was capable of increasing SOD expression in the cytoplasm of cells from spinal cord at 4h after intrathecal IL-1ß injection. SIGNIFICANCE: These results demonstrate that gp120 causes mechanical hyperalgesia and a peripheral increase in IL-1ß and IL-10, and that prior administration of limonene inhibits these changes. Also limonene modulates the activation of SOD expression in the spinal cord after spinal IL-1ß application. The ability of limonene to inhibit the mechanical hyperalgesia induced by gp120, TNF-α and IL-1ß emphasizes the anti-inflammatory action of limonene, specifically its ability to inhibit cytokine production and its consequences.
Asunto(s)
Antiinflamatorios no Esteroideos/farmacología , Ciclohexenos/farmacología , Proteína gp120 de Envoltorio del VIH/toxicidad , Hiperalgesia/prevención & control , Interleucina-1beta/toxicidad , Médula Espinal/efectos de los fármacos , Terpenos/farmacología , Factor de Necrosis Tumoral alfa/toxicidad , Administración Oral , Animales , Antiinflamatorios no Esteroideos/administración & dosificación , Western Blotting , Ciclohexenos/administración & dosificación , Ensayo de Inmunoadsorción Enzimática , Hiperalgesia/etiología , Hiperalgesia/metabolismo , Inyecciones Espinales , Limoneno , Masculino , Ratones , Médula Espinal/metabolismo , Terpenos/administración & dosificaciónRESUMEN
Geraniol (GER) is a monoterpene alcohol with various biochemical and pharmacological properties present in the essential oil of more than 160 species of herbs (especially the Cymbopogon genus). In this study, we evaluated the antinociceptive activity of GER in behavioural and electrophysiological in vitro experimental models of nociception using male Swiss mice. GER (12.5, 25 or 50 mg/kg i.p. and 50 or 200 mg/kg p.o.) reduced the number of writhes induced by acetic acid. The opioid antagonist naloxone (5 mg/kg s.c.) administered in mice subsequently treated with GER (25 mg/kg i.p.) did not reverse such antinociceptive activity, suggesting a non-opioid pathway for the mechanism of action. GER (12.5, 25 and 50 mg/kg i.p.) reduced paw licking time in the second phase of the formalin test. Also, in the glutamate test, GER when administered 50 mg/kg i.p. reduced paw licking time, probably modulating glutamatergic neurotransmission. GER blocked reversibly components of the compound action potential (CAP) recorded in isolated sciatic nerve in a concentration- and drug exposure time-dependent manner: 1 mM to 120 min. for the first component and 0.6 mM to 90 min. for the second component. The IC50 was calculated for the peak-to-peak amplitude (PPA) at 0.48 ± 0.04 mM. The conduction velocity was also reduced by exposure to GER starting from the concentration of 0.3 mM for both components of the CAP. In conclusion, it is suggested that GER has antinociceptive activity, especially in pain related to inflammation, and in part related to reduced peripheral nerve excitability.
Asunto(s)
Analgésicos/uso terapéutico , Modelos Animales de Enfermedad , Modelos Neurológicos , Neuritis/tratamiento farmacológico , Neuronas/efectos de los fármacos , Nervio Ciático/efectos de los fármacos , Terpenos/uso terapéutico , Potenciales de Acción/efectos de los fármacos , Monoterpenos Acíclicos , Administración Oral , Analgésicos/administración & dosificación , Analgésicos/farmacología , Animales , Conducta Animal/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Fenómenos Electrofisiológicos/efectos de los fármacos , Técnicas In Vitro , Inyecciones Intraperitoneales , Cinética , Masculino , Ratones , Conducción Nerviosa/efectos de los fármacos , Neuritis/inmunología , Neuronas/inmunología , Nervio Ciático/fisiología , Transmisión Sináptica/efectos de los fármacos , Terpenos/administración & dosificación , Terpenos/farmacologíaRESUMEN
BACKGROUND: Galectin-3 is known to be a lectin that plays an important role in inflammatory processes, acting as pro-inflammatory mediator in activation and migration of neutrophils and macrophages, as well as in the phagocytic function of these cells. The injection of mineral oils into the peritoneal cavity of mice, such as 2, 6, 10, 14-tetramethylpentadecane (pristane), induce a chronic granulomatous inflammatory reaction which is rich in macrophages, B cells and peritoneal plasma cells known as oil granuloma. In addition, this inflammatory microenvironment provided by oil granulomas is also an important site of plasmacytoma induction, which are dependent on cytokine production and cellular mobilization. Here, we have analyzed the role of galectin-3 in inflammatory cells mobilization and organization after pristane injection characterizing granulomatous reaction through the formation of oil granulomas. RESULTS: In galectin-3 deficient mice (gal-3(-/-)), the mobilization of inflammatory cells, between peritoneal cavity and bone marrow, was responsible for the formation of disorganized oil granulomas, which presented scattered cells, large necrotic areas and low amounts of extracellular matrix. The production of inflammatory cytokines partially explained the distribution of cells through peritoneal cavity, since high levels of IL-6 in gal-3(-/-) mice led to drastically reduction of B1 cells. The previous pro-inflammatory status of these animals also explains the excess of cell death and disruption of oil granulomas architecture. CONCLUSIONS: Our data indicate, for the first time, that the disruption in the inflammatory cells migration in the absence of galectin-3 is a crucial event in the formation and organization of oil granulomas.
Asunto(s)
Galectina 3/deficiencia , Granuloma/etiología , Terpenos/administración & dosificación , Animales , Citocinas/biosíntesis , Modelos Animales de Enfermedad , Matriz Extracelular , Granulocitos/inmunología , Granulocitos/metabolismo , Granulocitos/patología , Granuloma/metabolismo , Granuloma/patología , Mediadores de Inflamación/metabolismo , Inyecciones , Subgrupos Linfocitarios/inmunología , Subgrupos Linfocitarios/metabolismo , Subgrupos Linfocitarios/patología , Macrófagos Peritoneales/inmunología , Macrófagos Peritoneales/metabolismo , Ratones , Ratones Noqueados , Aceite Mineral/administración & dosificaciónRESUMEN
Geraniol (GR) is an acyclic monoterpene alcohol present in essential oils of aromatic plant species used in Brazilian folk medicine for the treatment of epilepsy. The present study was designed to evaluate the anticonvulsant effect of GR and of the inclusion complex geraniol:beta-cyclodextrin (GR:beta-CD). Mice were treated with GR or with GR:beta-CD (50, 100 and 200 mg/kg) 30 min before pentylenetetrazole (PTZ) or strychnine (STN). GR at 200 mg/kg and GR:beta-CD at the doses of 100 and 200 mg/kg significantly increased the latency for the first PTZ-induced convulsion and reduced the percentage of animals that convulsed. The pretreatment of flumazenil did not revert the anticonvulsant effect of GR in the PTZ-induced convulsion model. In the STN-induced convulsion model, the effects of GR were investigated and no difference was found against control. The results demonstrated an anticonvulsant activity of GR in the PTZ-model, which was potentialized by the complexation with beta-CD...
Geraniol (GR) es un alcohol monoterpeno acíclico presentes en los aceites esenciales de las especies de plantas aromáticas utilizadas en la medicina popular brasileña para el tratamiento de la epilepsia. El presente estudio fue diseñado para evaluar el efecto anticonvulsivo del GR y de la inclusión de geraniol complejo: beta-ciclodextrina (GR:beta-CD). Los ratones fueron tratados con GR o con GR:beta- CD (50, 100 y 200 mg/kg) 30 minutos antes de pentylenotetrazole (PTZ) o strichinine (STN). GR a 200 mg/kg y GR:beta-CD en las dosis de 100 y 200 mg/kg aumentó significativamente la latencia para la primera convulsión inducida PTZ-y redujo la porcentaje de animales que convulsionó. El tratamiento previo de flumazenil no revirtió el efecto anticonvulsivo de GR en el modelo de convulsión inducida con PTZ. En el modelo de convulsión inducida com STN, los efectos de GR fueron investigados y no se encontró ninguna diferencia contra el control. Los resultados demostraron una actividad anticonvulsiva de geraniol en el modelo de PTZ, que fue potenciada por la formación de complejos con beta-CD...
Asunto(s)
Animales , Ratones , Aceites Volátiles/administración & dosificación , Anticonvulsivantes/administración & dosificación , Epilepsia/tratamiento farmacológico , Terpenos/administración & dosificación , Ciclodextrinas , Fármacos Neuroprotectores/administración & dosificación , Monoterpenos/administración & dosificación , Pentilenotetrazol/administración & dosificaciónRESUMEN
PURPOSE: The purpose of this study was to verify the influence of prebrushing mouthwashes on dental plaque removal in children. METHODS: This study had a double-blind, randomized, controlled, crossover, 25-day experimental design, including 38 12- to 14-year-olds. Four solutions were used as prebrushing mouthwashes (Colgate Plax Magic, Listerine Cool Blue Agent, water and dye, and water) by each participant with seven days' washout. The plaque index was evaluated before and after tooth-brushing during the experimental period. RESULTS: Intergroup comparisons showed no significant differences in plaque reduction among evaluated solutions (Friedman test, P>.78). Significantly more plaque was present before vs. after tooth-brushing (Wilcoxon rank test, P<.001), independent of the surface (buccal or lingual/palatal). CONCLUSION: Use of prebrushing mouthwashes by children does not influence plaque removal by tooth-brushing.
Asunto(s)
Placa Dental/terapia , Antisépticos Bucales/uso terapéutico , Cepillado Dental/métodos , Adolescente , Antiinfecciosos Locales/administración & dosificación , Antiinfecciosos Locales/uso terapéutico , Bencenosulfonatos , Benzoatos/uso terapéutico , Niño , Colorantes , Estudios Cruzados , Índice de Placa Dental , Método Doble Ciego , Combinación de Medicamentos , Femenino , Estudios de Seguimiento , Humanos , Masculino , Antisépticos Bucales/administración & dosificación , Placebos , Salicilatos/administración & dosificación , Salicilatos/uso terapéutico , Dodecil Sulfato de Sodio/uso terapéutico , Terpenos/administración & dosificación , Terpenos/uso terapéuticoRESUMEN
Among the natural compounds, terpenoids play an important role in the drug discovery process for tropical diseases. The aim of the present work was to isolate antiprotozoal compounds from Ambrosia elatior and A. scabra. The sesquiterpene lactone (STL) cumanin was isolated from A. elatior whereas two other STLs, psilostachyin and cordilin, and one sterol glycoside, daucosterol, were isolated from A. scabra. Cumanin and cordilin were active against Trypanosoma cruzi epimastigotes showing 50% inhibition concentrations (IC50) values of 12 µM and 26 µM, respectively. Moreover, these compounds are active against bloodstream trypomastigotes, regardless of the T. cruzi strain tested. Psilostachyin and cumanin were also active against amastigote forms with IC50 values of 21 µM and 8 µM, respectively. By contrast, daucosterol showed moderate activity on epimastigotes and trypomastigotes and was inactive against amastigote forms. We also found that cumanin and psilostachyin exhibited an additive effect in their trypanocidal activity when these two drugs were tested together. Cumanin has leishmanicidal activity with growth inhibition values greater than 80% at a concentration of 5 µg/ml (19 µM), against both L. braziliensis and L. amazonensis promastigotes. In an in vivo model of T. cruzi infection, cumanin was more active than benznidazole, producing an 8-fold reduction in parasitemia levels during the acute phase of the infection compared with the control group, and more importantly, a reduction in mortality with 66% of the animals surviving, in comparison with 100% mortality in the control group. Cumanin also showed nontoxic effects at the doses assayed in vivo, as determined using markers of hepatic damage.
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Ambrosia/química , Antiprotozoarios/aislamiento & purificación , Antiprotozoarios/farmacología , Leishmania/efectos de los fármacos , Terpenos/aislamiento & purificación , Terpenos/farmacología , Trypanosoma cruzi/efectos de los fármacos , Animales , Antiprotozoarios/administración & dosificación , Supervivencia Celular/efectos de los fármacos , Interacciones Farmacológicas , Concentración 50 Inhibidora , Masculino , Ratones , Ratones Endogámicos C3H , Parasitemia/tratamiento farmacológico , Parasitemia/parasitología , Terpenos/administración & dosificaciónRESUMEN
The traditional use of essential oils in aromatherapy has offered numerous health benefits. However, few scientific studies have been conducted with these oils to confirm their therapeutic efficacy. (+)-Limonene is a chemical constituent of various bioactive essential oils. The present study reports on the anxiolytic-like effects of (+)-limonene in an elevated maze model of anxiety in mice. At concentrations of 0.5% and 1.0%, (+)-limonene, administered to mice by inhalation, significantly modified all the parameters evaluated in the elevated plus maze test. The pharmacological effect of inhaled (+)-limonene (1%) was not blocked by flumazenil. Analysis of (+)-limonene using gas chromatography-mass spectrometry (GC-MS) showed its volatility to be high. These data suggest possible connections between the volatility of (+)-limonene and its anxiolytic-like effect on the parameters evaluated in the elevated plus maze test. The data indicate that (+)-limonene could be used in aromatherapy as an antianxiety agent.
Asunto(s)
Ansiolíticos/farmacología , Productos Biológicos/farmacología , Ciclohexenos/farmacología , Alimentos , Plantas/química , Terpenos/farmacología , Administración por Inhalación , Animales , Ansiolíticos/administración & dosificación , Ansiolíticos/química , Productos Biológicos/administración & dosificación , Productos Biológicos/química , Ciclohexenos/administración & dosificación , Ciclohexenos/química , Interacciones Farmacológicas , Flumazenil/farmacología , Cromatografía de Gases y Espectrometría de Masas , Limoneno , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Ratones , Aceites Volátiles/química , Aceites Volátiles/farmacología , Terpenos/administración & dosificación , Terpenos/química , Factores de Tiempo , VolatilizaciónRESUMEN
AIM: To evaluate the clinical efficacy of subgingival ultrasonic instrumentation irrigated with essential oils (EOs) of residual periodontal pockets. MATERIAL AND METHODS: Sixty-four individuals with chronic periodontitis were invited to participate in this randomized, double-blind, parallel, and placebo-controlled clinical trial. All subjects received non-surgical periodontal therapy. After re-evaluation (baseline), residual pockets (pocket depth ≥5 mm) received test (ultrasonic instrumentation irrigated with EOs) or control therapy (ultrasonic instrumentation irrigated with negative control). Probing pocket depth (PPD), gingival recession (R), clinical attachment level (CAL), bleeding on probing (BOP), and plaque were assessed at baseline and after 4, 12, and 24 weeks. Differences between groups and changes over the course of time were analysed according to a generalized linear model. RESULTS: There was a significant reduction in PPD and BOP, as well as a significant CAL gain in the two groups (p<0.001). Nevertheless, there were no differences between the groups at any time of the study. When only initially deep pockets (PPD ≥7 mm) were analysed, a significantly greater CAL gain (p=0.03) and PPD reduction (p=0.01) was observed in the test group. CONCLUSION: The adjunctive use of EOs may promote significant CAL gain and PPD reduction in deep residual pockets.
Asunto(s)
Antiinfecciosos Locales/uso terapéutico , Aceites Volátiles/uso terapéutico , Bolsa Periodontal/terapia , Curetaje Subgingival/instrumentación , Terapia por Ultrasonido/instrumentación , Adulto , Antiinfecciosos Locales/administración & dosificación , Periodontitis Crónica/terapia , Ciclohexanoles/administración & dosificación , Ciclohexanoles/uso terapéutico , Placa Dental/microbiología , Método Doble Ciego , Combinación de Medicamentos , Etanol/administración & dosificación , Etanol/uso terapéutico , Eucaliptol , Eucalyptus , Femenino , Estudios de Seguimiento , Hemorragia Gingival/terapia , Recesión Gingival/terapia , Humanos , Masculino , Mentol/administración & dosificación , Mentol/uso terapéutico , Persona de Mediana Edad , Monoterpenos/administración & dosificación , Monoterpenos/uso terapéutico , Aceites Volátiles/administración & dosificación , Pérdida de la Inserción Periodontal/terapia , Placebos , Salicilatos/administración & dosificación , Salicilatos/uso terapéutico , Terpenos/administración & dosificación , Terpenos/uso terapéutico , Irrigación Terapéutica , Timol/administración & dosificación , Timol/uso terapéutico , Resultado del TratamientoRESUMEN
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by a progressive deterioration of cognitive abilities, amyloid-ß peptide (Aß) accumulation and synaptic alterations. Previous studies indicated that hyperforin, a component of the St John's Wort, prevents Aß neurotoxicity and some behavioral impairments in a rat model of AD. In this study we examined the ability of tetrahydrohyperforin (IDN5607), a stable hyperforin derivative, to prevent the cognitive deficit and synaptic impairment in an in vivo model of AD. In double transgenic APPswe/PSEN1ΔE9 mice, IDN5706 improves memory and prevents the impairment of synaptic plasticity in a dose-dependent manner, inducing a recovery of long-term potentiation. In agreement with these findings, IDN5706 prevented the decrease in synaptic proteins in hippocampus and cortex. In addition, decreased levels of tau hyperphosphorylation, astrogliosis, and total fibrillar and oligomeric forms of Aß were determined in double transgenic mice treated with IDN5706. In cultured cells, IDN5706 decreased the proteolytic processing of the amyloid precursor protein that leads to Aß peptide generation. These findings indicate that IDN5706 ameliorates AD neuropathology and could be considered of therapeutic relevance in AD treatment.
Asunto(s)
Enfermedad de Alzheimer/tratamiento farmacológico , Péptidos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Floroglucinol/análogos & derivados , Presenilina-1/genética , Procesamiento Proteico-Postraduccional , Transmisión Sináptica/genética , Terpenos/farmacología , Proteínas tau/metabolismo , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/prevención & control , Péptidos beta-Amiloides/antagonistas & inhibidores , Péptidos beta-Amiloides/genética , Precursor de Proteína beta-Amiloide/antagonistas & inhibidores , Precursor de Proteína beta-Amiloide/genética , Animales , Modelos Animales de Enfermedad , Ratones , Ratones Transgénicos , Floroglucinol/administración & dosificación , Floroglucinol/farmacología , Procesamiento Proteico-Postraduccional/genética , Transmisión Sináptica/efectos de los fármacos , Terpenos/administración & dosificaciónRESUMEN
The cardiovascular activity of essential oils has been reported. Some studies showed that the main chemical components of these oils contribute to their pharmacological activity. Therefore, the cardiovascular activity of four monoterpenes and one sesquiterpene was evaluated in the present work. In non-anaesthetized normotensive rats, (+)-alpha-pinene, (-)-beta-pinene, (+/-)-citronellol and (+/-)-linalool (1, 5, 10, and 20 mg/kg, i.v.) induced hypotension [maximal effect: (-35 +/- 3)%, (-46 +/- 4)%, (-48 +/- 2)% and (-40 +/- 2)%, respectively; n=6] and tachycardia [maximal effect: (13 +/- 4)%, (16 +/- 7)%, (21 +/- 1)% and (19 +/- 3)%, respectively; n=6] while (-)-a-bisabolol (1, 5, 10, and 20 mg/kg, i.v.) induced hypotension [maximal effect: (-47 +/- 8)%, n=6] and bradycardia [maximal effect: (-57 +/- 3)%]. In conclusion, these results demonstrated that all terpenes tested had hypotensive activity in rats and that the pharmacological effect of the terpene alcohols was more effective than that of the terpene hydrocarbons.
Asunto(s)
Antihipertensivos/farmacología , Aceites Volátiles/química , Terpenos/farmacología , Animales , Antihipertensivos/administración & dosificación , Antihipertensivos/aislamiento & purificación , Monoterpenos Bicíclicos , Presión Sanguínea/efectos de los fármacos , Bradicardia/inducido químicamente , Compuestos Bicíclicos con Puentes/farmacología , Frecuencia Cardíaca/efectos de los fármacos , Inyecciones Intravenosas , Masculino , Sesquiterpenos Monocíclicos , Monoterpenos/farmacología , Polietilenglicoles/administración & dosificación , Polietilenglicoles/farmacología , Ratas , Ratas Wistar , Sesquiterpenos/farmacología , Taquicardia/inducido químicamente , Terpenos/administración & dosificación , Terpenos/aislamiento & purificaciónRESUMEN
The present study investigated whether isopulegol, a monoterpene present in essential oils of several aromatic plants, would be able to promote some gastroprotective effect and also verified the possible mechanisms involved in this action. For this study, ethanol- and indomethacin-induced gastric ulcer models in mice and histopathological assessment were used. The roles of NO, sulfhydryls (glutathione, GSH), ATP-sensitive K(+) channels (K(ATP) channels), and prostaglandins were also investigated. Isopulegol exhibited a dose-related gastroprotective effect against ethanol-induced lesions, while the pretreatment with glibenclamide and indomethacin [but not with N(G)-nitro-L-arginine methyl ester] were able to reverse this action. The pretreatment with isopulegol also restored GSH levels to normal levels and exhibited dose-related gastroprotective effect against indomethacin-induced ulcer. The results suggested that isopulegol presents significant gastroprotective effects in both ethanol- and indomethacin-induced ulcer models, which appear to be mediated, at least in part, by endogenous prostaglandins, K(ATP) channel opening, and antioxidant properties.
Asunto(s)
Antioxidantes/farmacología , Úlcera Gástrica/prevención & control , Terpenos/farmacología , Animales , Antioxidantes/administración & dosificación , Monoterpenos Ciclohexánicos , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Etanol/toxicidad , Glutatión/efectos de los fármacos , Glutatión/metabolismo , Indometacina/toxicidad , Canales KATP/metabolismo , Masculino , Ratones , Prostaglandinas/metabolismo , Úlcera Gástrica/inducido químicamente , Terpenos/administración & dosificaciónRESUMEN
Essential oil from Citrus aurantium and the monoterpene limonene are widely used flavoring agents that are found in some common food items. This specie is also used medicinally throughout the world to treat gastritis and gastric disorders. Therefore, biological assays were performed in vivo on essential oil of C. aurantium (OEC) and its majority compound limonene (LIM) to evaluate their effect on gastric mucosa. The OEC (250 mg/kg, p.o.) and LIM (245 mg/kg, p.o.) provided effective (99%) gastroprotection against lesions induced by absolute ethanol and NSAID (non-steroidal anti-inflammatory drug) in rats. OEC and LIM do not interfere with gastric H(+) secretion, serum gastrin or glutathione (GSH) level in gastric mucosa. But the gastroprotective action of OEC and LIM occurs due to an increase in the gastric mucus production induced by conserving the basal PGE(2) levels after challenge by agents harmful to the gastric mucosa. Given that LIM and OEC are excellent flavoring agents and also present gastroprotective actions, they can be regarded as a promising target for the development of a new drug for the prevention of gastric damage.