RESUMEN
Research on bioactive compounds is essential to improve human health; promote adequate nutrition; drive innovation in the food, agricultural and biotechnology industries; and contribute to the preservation of the environment. The genus Diplotaxis (Brassicaceae) currently comprises around forty species, some of which are edible, particularly Diplotaxis tenuifolia (wild rocket), Diplotaxis erucoides (wall rocket), Diplotaxis muralis (annual wall rocket), Diplotaxis viminea (perennial wall rocket), and Diplotaxis simplex. The leaves of these species are rich in fiber and essential minerals, such as calcium, iron, potassium, and magnesium. Thirteen species have been characterized for their phenolic compounds, predominantly kaempferol, quercetin, and isorhamnetin glycosides. Furthermore, glucosinolate compounds were identified in nineteen species of the genus Diplotaxis. Many of the phytochemicals identified in Diplotaxis spp. demonstrated interesting biological activities, such as antioxidant, anti-inflammatory, antibacterial, hypoglycemic and hypolipidemic effects, as well as cytotoxicity and antiproliferative properties. This article provides a review of the phytochemistry of the Diplotaxis genus, highlighting its importance in food, its biological properties, potential pharmacological applications, and the dearth of research on many of these plants.
Asunto(s)
Brassicaceae , Fitoquímicos , Fitoquímicos/química , Fitoquímicos/farmacología , Humanos , Brassicaceae/química , Extractos Vegetales/química , Extractos Vegetales/farmacología , Antioxidantes/farmacología , Antioxidantes/química , Valor Nutritivo , Hojas de la Planta/químicaRESUMEN
Aromatic plants and their essential oils have shown beneficial effects on the cardiovascular system and, therefore, are potential raw materials in the development of functional foods. However, despite their undeniable potential, essential oils present several limitations that need to be addressed, such as stability, poor solubility, undesirable sensory effects, and low bioavailability. The present review provides a current state-of-the-art on the effects of volatile extracts obtained from aromatic plants on the cardiovascular system and focuses on major challenges that need to be addressed to increase their use in food products. Moreover, strategies underway to overcome these limitations are pointed out, thus anticipating a great appreciation of these extracts in the functional food industry.
Asunto(s)
Enfermedades Cardiovasculares , Aceites Volátiles , Alimentos Funcionales , Aceites de Plantas , Enfermedades Cardiovasculares/tratamiento farmacológico , Aceites Volátiles/uso terapéutico , Aceites Volátiles/farmacología , Plantas , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéuticoRESUMEN
The treatment of dermatophytoses, the most common human fungal infections, requires new alternatives. The aim of this study was to determine the antidermatophytic activity of the aqueous Azorean Black Tea extract (ABT), together with an approach to the mechanisms of action. The phytochemical analysis of ABT extract was performed by HPLC. The dermatophytes susceptibility was assessed using a broth microdilution assay; potential synergies with terbinafine and griseofulvin were evaluated by the checkerboard assay. The mechanism of action was appraised by the quantification of the fungal cell wall chitin and ß-1,3-glucan, and by membrane ergosterol. The presence of ultrastructural modifications was studied by Transmission Electron Microscopy (TEM). The ABT extract contained organic and phenolic acids, flavonoids, theaflavins and alkaloids. It showed an antidermatophytic effect, with MIC values of 250 µg/mL for Trichophyton mentagrophytes, 125 µg/mL for Trichophyton rubrum and 500 µg/mL for Microsporum canis; at these concentrations, the extract was fungicidal. An additive effect of ABT in association to terbinafine on these three dermatophytes was observed. The ABT extract caused a significant reduction in ß-1,3-glucan content, indicating the synthesis of this cell wall component as a possible target. The present study identifies the antidermatophytic activity of the ABT and highlights its potential to improve the effectiveness of conventional topical treatment currently used for the management of skin or mucosal fungal infections.
Asunto(s)
Arthrodermataceae , Camellia sinensis , Fungicidas Industriales , Micosis , Humanos , Antifúngicos/química , Terbinafina/farmacología , Té , Pruebas de Sensibilidad Microbiana , Fungicidas Industriales/farmacología , Extractos Vegetales/farmacología , Micosis/tratamiento farmacológico , TrichophytonRESUMEN
For the first time, the present study unravels a cardiospecific therapeutic approach for Pulmonary Arterial Hypertension (PAH), a disease with a very poor prognosis and high mortality rates due to right ventricle (RV) dysfunction. We first established a new in vitro model of high-pressure-induced hypertrophy that closely resembles heart defects associated with PAH and validated our in vitro findings on a preclinical in vivo model of monocrotaline (MCT)-induced PAH. Our results showed the in vitro antihypertrophic effect of 1,8-cineole, a monoterpene widely found in several essential oils. Also, a decrease in RV hypertrophy and fibrosis, and an improvement in heart function in vivo was observed, when 1,8-cineole was applied topically. Furthermore, 1,8-cineole restored gap junction protein connexin43 distribution at the intercalated disks and mitochondrial functionality, suggesting it may act by preserving cardiac cell-to-cell communication and bioenergetics. Overall, our results point out a promising therapeutic compound that can be easily applied topically, thus paving the way for the development of effective cardiac-specific therapies to greatly improve PAH outcomes.
Asunto(s)
Cardiomiopatías , Hipertensión Pulmonar , Hipertensión Arterial Pulmonar , Disfunción Ventricular Derecha , Animales , Conexina 43 , Modelos Animales de Enfermedad , Eucaliptol/uso terapéutico , Ventrículos Cardíacos/metabolismo , Homeostasis , Humanos , Hipertensión Pulmonar/tratamiento farmacológico , Hipertrofia Ventricular Derecha/metabolismo , Hipertensión Arterial Pulmonar/tratamiento farmacológico , Disfunción Ventricular Derecha/metabolismoRESUMEN
Alzheimer's disease (AD) is the most common neurodegenerative disorder affecting elderly people worldwide. Currently, there are no effective treatments for AD able to prevent disease progression, highlighting the urgency of finding new therapeutic strategies to stop or delay this pathology. Several plants exhibit potential as source of safe and multi-target new therapeutic molecules for AD treatment. Meanwhile, Eucalyptus globulus extracts revealed important pharmacological activities, namely antioxidant and anti-inflammatory properties, which can contribute to the reported neuroprotective effects. This review summarizes the chemical composition of essential oil (EO) and phenolic extracts obtained from Eucalyptus globulus leaves, disclosing major compounds and their effects on AD-relevant pathological features, including deposition of amyloid-ß (Aß) in senile plaques and hyperphosphorylated tau in neurofibrillary tangles (NFTs), abnormalities in GABAergic, cholinergic and glutamatergic neurotransmission, inflammation, and oxidative stress. In general, 1,8-cineole is the major compound identified in EO, and ellagic acid, quercetin, and rutin were described as main compounds in phenolic extracts from Eucalyptus globulus leaves. EO and phenolic extracts, and especially their major compounds, were found to prevent several pathological cellular processes and to improve cognitive function in AD animal models. Therefore, Eucalyptus globulus leaves are a relevant source of biological active and safe molecules that could be used as raw material for nutraceuticals and plant-based medicinal products useful for AD prevention and treatment.
Asunto(s)
Enfermedad de Alzheimer , Aceites Volátiles , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/patología , Animales , Biomasa , Bosques , Humanos , Aceites Volátiles/farmacología , Aceites Volátiles/uso terapéutico , Fenoles/farmacologíaRESUMEN
Respiratory mycosis is a major health concern, due to the expanding population of immunosuppressed and immunocompromised patients and the increasing resistance to conventional antifungals and their undesired side-effects, thus justifying the development of new therapeutic strategies. Plant metabolites, namely essential oils, represent promising preventive/therapeutic strategies due to their widely reported antifungal potential. However, regarding fungal infections of the respiratory tract, information is disperse and no updated compilation on current knowledge is available. Therefore, the present review aims to gather and systematize relevant information on the antifungal effects of several essential oils and volatile compounds against the main type of respiratory mycosis that impact health care systems. Particular attention is paid to Aspergillus fumigatus, the main pathogen involved in aspergillosis, Candida auris, currently emerging as a major pathogen in certain parts of the world, and Cryptococcus neoformans, one of the main pathogens involved in pulmonary cryptococcosis. Furthermore, the main mechanisms of action underlying essential oils' antifungal effects and current limitations in clinical translation are presented. Overall, essential oils rich in phenolic compounds seem to be very effective but clinical translation requires more comprehensive in vivo studies and human trials to assess the efficacy and tolerability of these compounds in respiratory mycosis.
Asunto(s)
Micosis , Aceites Volátiles , Trastornos Respiratorios , Animales , Antifúngicos/uso terapéutico , Humanos , Micosis/tratamiento farmacológico , Aceites de Plantas , Trastornos Respiratorios/tratamiento farmacológicoRESUMEN
Ficus genus is typically tropical plants and is among the earliest fruit trees cultivated by humans. Ficus carica L. is the common fig, Ficus benjamina L. is the weeping fig, and Ficus pumila L. is the creeping fig. These species are commonly used in traditional medicine for a wide range of diseases and contain rich secondary metabolites that have shown diverse applications. This comprehensive review describes for Ficus genus the phytochemical compounds, traditional uses and contemporary pharmacological activities such as antioxidant, cytotoxic, antimicrobial, anti-inflammatory, antidiabetic, antiulcer, and anticonvulsant. An extended survey of the current literature (Science Direct, Scopus, PubMed) has been carried out as part of the current work. The trends in the phytochemistry, pharmacological mechanisms and activities of Ficus genus are overviewed in this manuscript: antimicrobial, antidiabetic, anti-inflammatory and analgesic activity, antiseizure and anti-Parkinson's diseases, cytotoxic and antioxidant. Health-promoting effects, recent human clinical studies, safety and adverse effects of Ficus plants also are covered. The medical potential and long-term pharmacotherapeutic use of the genus Ficus along with no serious reported adverse events, suggests that it can be considered as being safe.
Asunto(s)
Ficus/química , Fitoquímicos/uso terapéutico , Extractos Vegetales/uso terapéutico , Humanos , Fitoquímicos/farmacología , Extractos Vegetales/farmacologíaRESUMEN
Cardiovascular diseases (CVDs) are a global health burden that greatly impact patient quality of life and account for a huge number of deaths worldwide. Despite current therapies, several side effects have been reported that compromise patient adherence; thus, affecting therapeutic benefits. In this context, plant metabolites, namely volatile extracts and compounds, have emerged as promising therapeutic agents. Indeed, these compounds, in addition to having beneficial bioactivities, are generally more amenable and present less side effects, allowing better patient tolerance. The present review is an updated compilation of the studies carried out in the last 20 years on the beneficial potential of essential oils, and their compounds, against major risk factors of CVDs. Overall, these metabolites show beneficial potential through a direct effect on these risk factors, namely hypertension, dyslipidemia and diabetes, or by acting on related targets, or exerting general cellular protection. In general, monoterpenic compounds are the most studied regarding hypotensive and anti-dyslipidemic/antidiabetic properties, whereas phenylpropanoids are very effective at avoiding platelet aggregation. Despite the number of studies performed, clinical trials are sparse and several aspects related to essential oil's features, namely volatility and chemical variability, need to be considered in order to guarantee their efficacy in a clinical setting.
Asunto(s)
Enfermedades Cardiovasculares/tratamiento farmacológico , Diabetes Mellitus/tratamiento farmacológico , Dislipidemias/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Aceites Volátiles/uso terapéutico , Agregación Plaquetaria/efectos de los fármacos , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/metabolismo , Enfermedades Cardiovasculares/patología , Diabetes Mellitus/metabolismo , Diabetes Mellitus/patología , Dislipidemias/complicaciones , Dislipidemias/metabolismo , Dislipidemias/patología , Humanos , Aceites Volátiles/química , Estrés Oxidativo , Calidad de Vida , Factores de RiesgoAsunto(s)
Hipertensión Arterial Pulmonar , Humanos , Eucaliptol , Ventrículos Cardíacos , Conexina 43 , HomeostasisRESUMEN
Aiming for discovering effective and harmless antitrypanosomal agents, 17 essential oils and nine major components were screened for their effects on T. b. brucei. The essential oils were obtained by hydrodistillation from fresh plant material and analyzed by GC and GC-MS. The trypanocidal activity was assessed using blood stream trypomastigotes cultures of T. b. brucei and the colorimetric resazurin method. The MTT test was used to assess the cytotoxicity of essential oils on macrophage cells and Selectivity Indexes were calculated. Of the 17 essential oils screened three showed high trypanocidal activity (IC50â¯<â¯10⯵g/mL): Juniperus oxycedrus (IC50 of 0.9⯵g/mL), Cymbopogon citratus (IC50 of 3.2⯵g/mL) and Lavandula luisieri (IC50 of 5.7⯵g/mL). These oils had no cytotoxic effects on macrophage cells showing the highest values of Selectivity Index (63.4, 9.0 and 11.8, respectively). The oils of Distichoselinum tenuifolium, Lavandula viridis, Origanum virens, Seseli tortuosom, Syzygium aromaticum, and Thymbra capitata also exhibited activity (IC50 of 10-25⯵g/mL) but showed cytotoxicity on macrophages. Of the nine compounds tested, α-pinene (IC50 of 2.9⯵g/mL) and citral (IC50 of 18.9⯵g/mL) exhibited the highest anti-trypanosomal activities. Citral is likely the active component of C. citratus and α-pinene is responsible for the antitrypanosomal effects of J. oxycedrus. The present work leads us to propose the J. oxycedrus, C. citratus and L. luisieri oils as valuable sources of new molecules for African Sleeping Sickness treatment.
Asunto(s)
Aceites Volátiles/farmacología , Trypanosoma brucei brucei/efectos de los fármacos , Línea Celular , Cymbopogon/química , Cromatografía de Gases y Espectrometría de Masas , Concentración 50 Inhibidora , Juniperus/química , Lavandula/química , Macrófagos/efectos de los fármacos , Aceites Volátiles/química , Aceites Volátiles/toxicidad , Extractos Vegetales/química , Extractos Vegetales/farmacología , Extractos Vegetales/toxicidadRESUMEN
The increased incidence of fungal infections, associated with the widespread use of antifungal drugs, has resulted in the development of resistance, making it necessary to discover new therapeutic alternatives. Among fungal infections, dermatophytoses constitute a serious public health problem, affecting 20-25 % of the world population. Medicinal plants represent an endless source of bioactive molecules, and their volatile and non-volatile extracts are clearly recognized for being the historical basis of therapeutic health care. Because of this, the research on natural products with antifungal activity against dermatophytes has considerably increased in recent years. However, despite the recognized anti-dermatophytic potential of natural products, often advantageous face to commercial drugs, there is still a long way to go until their use in therapeutics. This review attempts to summarize the current status of anti-dermatophytic natural products, focusing on their mechanism of action, the developed pharmaceutical formulations and their effectiveness in human and animal models of infection.
Asunto(s)
Antifúngicos/farmacología , Arthrodermataceae/efectos de los fármacos , Productos Biológicos/farmacología , Tiña/tratamiento farmacológico , Animales , Antifúngicos/aislamiento & purificación , Antifúngicos/uso terapéutico , Productos Biológicos/aislamiento & purificación , Productos Biológicos/uso terapéutico , Descubrimiento de Drogas/métodos , Descubrimiento de Drogas/tendencias , Humanos , Fitoquímicos/aislamiento & purificación , Fitoquímicos/farmacología , Fitoquímicos/uso terapéutico , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Plantas/química , Tiña/microbiologíaRESUMEN
The composition of the essential oil (EO) of Thapsia villosa (Apiaceae), isolated by hydrodistillation from the plant's aerial parts, was analysed by GC and GC-MS. Antifungal activity of the EO and its main components, limonene (57.5%) and methyleugenol (35.9%), were evaluated against clinically relevant yeasts (Candida spp., Cryptococcus neoformans and Malassezia furfur) and moulds (Aspergillus spp. and dermatophytes). Minimum inhibitory concentrations (MICs) were measured according to the broth macrodilution protocols by Clinical and Laboratory Standards Institute (CLSI). The EO, limonene and methyleugenol displayed low MIC and MFC (minimum fungicidal concentration) values against Candida spp., Cryptococcus neoformans, dermatophytes, and Aspergillus spp. Regarding Candida species, an inhibition of yeast-mycelium transition was demonstrated at sub-inhibitory concentrations of the EO (MIC/128; 0.01 µL/mL) and their major compounds in Candida albicans. Fluconazole does not show this activity, and the combination with low concentrations of EO could associate a supplementary target for the antifungal activity. The association of fluconazole with T. villosa oil does not show antagonism, but the combination limonene/fluconazole displays synergism. The fungistatic and fungicidal activities revealed by T. villosa EO and its main compounds, associated with their low haemolytic activity, confirm their potential antimicrobial interest against fungal species often associated with human mycoses.
Asunto(s)
Antifúngicos/farmacología , Arthrodermataceae/efectos de los fármacos , Aspergillus/efectos de los fármacos , Candida/efectos de los fármacos , Malassezia/efectos de los fármacos , Aceites Volátiles/farmacología , Thapsia/química , Pruebas de Sensibilidad Microbiana , Aceites Volátiles/químicaRESUMEN
A new C15-acetogenin, sagonenyne (20), exhibiting an unusual single tetrahydropyran ring was isolated from an ethyl acetate extract of Laurencia obtusa collected on the Corsican coastline. Its structure was established by detailed NMR spectroscopic analysis, mass spectrometry, and comparison with literature data. Twenty-three known compounds were identified in the same extract by means of column chromatography steps, using a 13C-NMR computer aided method developed in our laboratory. In addition to sesquiterpenes, which represent the main chemical class of this extract, diterpenes, sterols, and C15-acetogenins were identified. The crude extract was submitted to a cytotoxicity assay and was particularly active against THP-1 cells, a human leukemia monocytic cell line.
Asunto(s)
Acetogeninas/química , Citotoxinas/química , Diterpenos/química , Laurencia/química , Sesquiterpenos/química , Esteroles/química , Acetogeninas/aislamiento & purificación , Acetogeninas/farmacología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Citotoxinas/aislamiento & purificación , Citotoxinas/farmacología , Diterpenos/aislamiento & purificación , Diterpenos/farmacología , Francia , Humanos , Espectroscopía de Resonancia Magnética , Extractos Vegetales/química , Sesquiterpenos/aislamiento & purificación , Sesquiterpenos/farmacología , Esteroles/aislamiento & purificación , Esteroles/farmacología , Células THP-1RESUMEN
The genus Myrtus L. (Myrtaceae family) comprises two species, Myrtus communis L. (known as common myrtle) growing wild all around the Mediterranean basin and Myrtus nivellei Batt. and Trab. (known as Saharan myrtle), found in central Sahara. Only one country, Algeria, hosts both species, M. communis in the North and M. nivellei in the South. The aim of this review was to collect, summarize, and compare the main results reported relative to the essential oils isolated from aerial parts of both species: botanical aspects, habitat, traditional use, chemical composition, new compounds, antimicrobial activity, antioxidant activity, anti-inflammatory effect, and insecticidal activity. Both essential oils have potential applications in human health.
Asunto(s)
Myrtus/química , Aceites Volátiles/química , Aceites Volátiles/farmacología , Argelia , Animales , Antibacterianos/química , Antibacterianos/aislamiento & purificación , Antibacterianos/farmacología , Antiinflamatorios/química , Antiinflamatorios/aislamiento & purificación , Antiinflamatorios/farmacología , Antifúngicos/química , Antifúngicos/aislamiento & purificación , Antifúngicos/farmacología , Antioxidantes/química , Antioxidantes/aislamiento & purificación , Antioxidantes/farmacología , Bacterias/efectos de los fármacos , Escarabajos/efectos de los fármacos , Hongos/efectos de los fármacos , Humanos , Insecticidas/química , Insecticidas/aislamiento & purificación , Insecticidas/farmacología , Myrtus/crecimiento & desarrollo , Aceites Volátiles/aislamiento & purificación , Especificidad de la EspecieRESUMEN
CONTEXT: Effective drugs to treat osteoarthritis (OA) and inflammatory bowel disease (IBD) are needed. OBJECTIVE: To identify essential oils (EOs) with anti-inflammatory activity in cell models of OA and IBD. MATERIALS AND METHODS: EOs from Eryngium duriaei subsp. juresianum (M. Laínz) M. Laínz (Apiaceae), Laserpitium eliasii subsp. thalictrifolium Sennen & Pau (Apiaceae), Lavandula luisieri (Rozeira) Rivas-Martínez (Lamiaceae), Othantus maritimus (L.) Hoff. & Link (Asteraceae), and Thapsia villosa L. (Apiaceae) were analyzed by GC and GC/MS. The anti-inflammatory activity of EOs (5-200 µg/mL) was evaluated by measuring inducible nitric oxide synthase (iNOS) and nuclear factor-κB (NF-κB) activation (total and phosphorylated IκB-α), in primary human chondrocytes and the intestinal cell line, C2BBe1, stimulated with interleukin-1ß (IL-1ß) or interferon-γ (IFN-γ), IL-1ß and tumor necrosis factor-α (TNF-α), respectively. RESULTS: The EO of L. luisieri significantly reduced iNOS (by 54.9 and 81.0%, respectively) and phosphorylated IκB-α (by 87.4% and 62.3%, respectively) in both cell models. The EO of E. duriaei subsp. juresianum caused similar effects in human chondrocytes, but was inactive in intestinal cells, even at higher concentrations. The EOs of L. eliasii subsp. thalictrifolium and O. maritimus decreased iNOS expression by 45.2 ± 8.7% and 45.2 ± 6.2%, respectively, in C2BBe1 cells and were inactive in chondrocytes. The EO of T. villosa was inactive in both cell types. DISCUSSION AND CONCLUSION: This is the first study showing anti-inflammatory effects of the EOs of L. luisieri and E. duriaei subsp. juresianum. These effects are specific of the cell type and may be valuable to develop new therapies or as sources of active compounds with improved efficacy and selectivity towards OA and IBD.
Asunto(s)
Antiinflamatorios/farmacología , Condrocitos/efectos de los fármacos , Eryngium , Lavandula , Aceites Volátiles/farmacología , Adulto , Anciano , Antiinflamatorios/aislamiento & purificación , Antiinflamatorios/uso terapéutico , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/fisiología , Células Cultivadas , Condrocitos/metabolismo , Condrocitos/patología , Enfermedad Crónica , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Inflamación/patología , Masculino , Persona de Mediana Edad , Aceites Volátiles/aislamiento & purificación , Aceites Volátiles/uso terapéutico , Componentes Aéreos de las Plantas , Aceites de Plantas/aislamiento & purificación , Aceites de Plantas/farmacología , Aceites de Plantas/uso terapéutico , Resultado del Tratamiento , Adulto JovenRESUMEN
Previous studies have suggested that α-pinene, a common volatile plant metabolite, may have anti-inflammatory effects in human chondrocytes, thus exhibiting potential antiosteoarthritic activity. The objective of this study was to further characterize the potential antiosteoarthritic activity of selected pinene derivatives by evaluating their ability to modulate inflammation and extracellular matrix remodeling in human chondrocytes and to correlate the biological and chemical properties by determining whether the effects are isomer- and/or enantiomer-selective. To further elucidate chemicopharmacological interactions, the activities of other naturally occurring monoterpenes with the pinane nucleus were also investigated. At noncytotoxic concentrations, (+)-α-pinene (1) elicited the most potent inhibition of the IL-1ß-induced inflammatory and catabolic pathways, namely, NF-κB and JNK activation and the expression of the inflammatory (iNOS) and catabolic (MMP-1 and -13) genes. (-)-α-Pinene (2) was less active than the (+)-enantiomer (1), and ß-pinene (3) was inactive. E-Pinane (4) and oxygenated pinane-derived compounds, pinocarveol (5), myrtenal (6), (E)-myrtanol (7), myrtenol (8), and (Z)-verbenol (9), were less effective or even completely inactive and more cytotoxic than the pinenes tested (1-3). The data obtained show isomer- and enantiomer-selective anti-inflammatory and anticatabolic effects of α-pinene in human chondrocytes, (+)-α-pinene (1) being the most promising for further studies to determine its potential value as an antiosteoarthritic drug.
Asunto(s)
Antiinflamatorios/farmacología , Condrocitos/efectos de los fármacos , Monoterpenos/farmacología , Osteoartritis/tratamiento farmacológico , Antiinflamatorios/química , Monoterpenos Bicíclicos , Humanos , Interleucina-1beta/metabolismo , MAP Quinasa Quinasa 4/efectos de los fármacos , Estructura Molecular , Monoterpenos/química , FN-kappa B/antagonistas & inhibidores , Óxido Nítrico Sintasa de Tipo II/efectos de los fármacos , Estereoisomerismo , Terpenos/farmacologíaRESUMEN
BACE-1 is an aspartic protease involved in the conversion of amyloid precursor protein (APP) to amyloid-ß (Aß) in vivo, which is one of the key steps in the development and progression of Alzheimer's disease. In a previous screening procedure for inhibitors of BACE-1 activity, the oil of Lavandula luisieri was identified as the most potent among several essential oils. The inhibitory effect of this essential oil on Aß production was also demonstrated in a cellular assay. The composition of the volatile oil and the isolation of the compound responsible for the inhibitory activity were also reported. The present work focused on the characterization of the inhibition of BACE-1 by this active compound, a monoterpene necrodane ketone, 2,3,4,4-tetramethyl-5-methylenecyclopent-2-enone (1), with assessment of its Ki value and the type of inhibition. The dose-related effects of the compound were also evaluated using two different cell lines, with determinations of the respective EC50 values. The entire oil and the 2,3,4,4-tetramethyl-5-methylenecyclopent-2-enone (1) were tested on a triple transgenic mouse model of Alzheimer's disease. The overall results showed that compound 1 displayed a dose-dependent inhibition of BACE-1 in cellular and mouse models of Alzheimer's disease and is therefore capable of passing through cellular membranes and the blood-brain barrier.
Asunto(s)
Enfermedad de Alzheimer/metabolismo , Proteasas de Ácido Aspártico/antagonistas & inhibidores , Lavandula/química , Monoterpenos/aislamiento & purificación , Monoterpenos/farmacología , Péptidos beta-Amiloides/análisis , Péptidos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Animales , Barrera Hematoencefálica/metabolismo , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Catepsina D/antagonistas & inhibidores , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Ratones , Estructura Molecular , Monoterpenos/química , Monoterpenos/farmacocinética , Aceites de Plantas/químicaRESUMEN
The chemical composition of the essential oil isolated from the aerial parts of Melampodium divaricatum (Rich.) DC. (Asteraceae) was characterized by GC-FID and GC/MS analyses. (E)-Caryophyllene (56.0%), germacrene D (12.7%), and bicyclogermacrene (9.2%) were identified as the major oil components. The antimicrobial activity of the oil against seven standard strains of oral pathogens from the American Type Culture Collection (ATCC) was evaluated by determining minimum inhibitory concentrations (MICs) using the microdilution method. MIC Values below 100â µg/ml were obtained against Streptococcus sobrinus (90â µg/ml), Lactobacillus casei (30â µg/ml), S. mutans (20â µg/ml), and S. mitis (18â µg/ml). In contrast, the MIC values of the major oil compound (E)-caryophyllene were higher than 400â µg/ml against all pathogens, suggesting that the activity of the oil might depend on minor oil components and/or on synergistic effects. The M. divaricatum essential oil is a promising agent to include in anticariogenic oral rinse formulations for the control of oral pathogens.
Asunto(s)
Antiinfecciosos/química , Asteraceae/química , Aceites Volátiles/química , Antiinfecciosos/aislamiento & purificación , Antiinfecciosos/farmacología , Asteraceae/metabolismo , Lacticaseibacillus casei/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Aceites Volátiles/aislamiento & purificación , Aceites Volátiles/farmacología , Componentes Aéreos de las Plantas/química , Componentes Aéreos de las Plantas/metabolismo , Streptococcus mitis/efectos de los fármacos , Streptococcus mutans/efectos de los fármacos , Streptococcus sobrinus/efectos de los fármacosRESUMEN
Plant tissue culture has evolved in the last decades with several types of cultures being developed to promote a more sustainable food production system. Moreover, these cultures can be applied for the production of relevant metabolites with medicinal potential, thus contributing to nutrition and healthcare. Importantly, plant micropropagation has enabled agricultural expansion and tissue culture has emerged as a promising production alternative for several plants and their metabolites in the food, cosmetic, and pharmaceutical industries. Plant tissue cultures present several advantages over conventional propagation techniques as they are season independent, enabling a continuous supply of the plants/compounds of interest, with the guarantee of high phytosanitary quality. In addition, genetic uniformity is generally maintained, thus reducing chemical variability that can compromise safety and efficacy. Nevertheless, despite their undeniable potential, with many researchers focusing on new strategies to improve production yield in cell cultures, such as with the use of elicitors or resorting to metabolomics engineering, an effective and lucrative large-scale production has yet to be obtained. Indeed, only a few compounds with market value are produced in this regard and several limitations such as contaminations, low culture yield and production costs still need to be overcome in order to take advantage of the full potential of these techniques.
Asunto(s)
Técnicas de Cultivo de Tejidos , Técnicas de Cultivo de Tejidos/métodos , Técnicas de Cultivo de Tejidos/tendencias , Plantas/metabolismoRESUMEN
Ageing is a natural process characterized by a time-dependent decline of physiological integrity that compromises functionality and inevitably leads to death. This decline is also quite relevant in major human pathologies, being a primary risk factor in neurodegenerative diseases, metabolic disorders, cardiovascular diseases and musculoskeletal disorders. Bearing this in mind, it is not surprising that research aiming at improving human health during this process has burst in the last decades. Importantly, major hallmarks of the ageing process and phenotype have been identified, this knowledge being quite relevant for future studies towards the identification of putative pharmaceutical targets, enabling the development of preventive/therapeutic strategies to improve health and longevity. In this context, aromatic plants have emerged as a source of potential bioactive volatile molecules, mainly monoterpenes, with many studies referring to their anti-ageing potential. Nevertheless, an integrated review on the current knowledge is lacking, with several research approaches studying isolated ageing hallmarks or referring to an overall anti-ageing effect, without depicting possible mechanisms of action. Herein, we aim to provide an updated systematization of the bioactive potential of volatile monoterpenes on recently proposed ageing hallmarks, and highlight the main mechanisms of action already identified, as well as possible chemical entity-activity relations. By gathering and categorizing the available scattered information, we also aim to identify important research gaps that could help pave the way for future research in the field.