RESUMEN
The present study aimed to evaluate the protective potential of carvacrol against depressive-like behavior and cognitive impairment prompted by chronic unpredictable mild stress (CUMS) in mice. The animals were divided into six groups: Control (non-stressed), CARV (carvacrol at 50â¯mg/kg, p.o.), FLU (fluoxetine at 10â¯mg/kg, p.o.), CUMS (stressed), CUMS + CARV and CUMS + FLU, and the groups with CUMS were subjected to different stressors for 28 days. After treatment, mice underwent behavioral testing (open field, forced swimming, sucrose preference, social interaction, novel object recognition and Y-maze) and brain areas were removed for oxidative stress (MDA, nitrite/nitrate and GSH levels) and cytokine (IL-1ß and TNF-α) content assays. The results revealed that CARV administration reversed depressive-like behavior and significantly ameliorated the cognitive deficit induced by CUMS, as well as was able to attenuate oxidative stress (decreased MDA and nitrite/nitrate levels and increased GSH levels). In addition, a significant reduction in hippocampal IL-1ß and TNF-α levels was observed, demonstrating a potential anti-neuroinflammatory activity. Taken together, the antioxidant and anti-inflammatory activities observed in this study indicate that CARV is a promising drug for antidepressant treatment.
Asunto(s)
Conducta Animal , Disfunción Cognitiva , Cimenos , Depresión , Modelos Animales de Enfermedad , Enfermedades Neuroinflamatorias , Estrés Oxidativo , Estrés Psicológico , Animales , Estrés Oxidativo/efectos de los fármacos , Ratones , Disfunción Cognitiva/tratamiento farmacológico , Disfunción Cognitiva/etiología , Disfunción Cognitiva/metabolismo , Depresión/tratamiento farmacológico , Depresión/metabolismo , Depresión/etiología , Masculino , Estrés Psicológico/tratamiento farmacológico , Estrés Psicológico/complicaciones , Estrés Psicológico/metabolismo , Cimenos/farmacología , Cimenos/administración & dosificación , Conducta Animal/efectos de los fármacos , Enfermedades Neuroinflamatorias/tratamiento farmacológico , Enfermedades Neuroinflamatorias/metabolismo , Antidepresivos/farmacología , Antidepresivos/administración & dosificación , Antioxidantes/farmacología , Fluoxetina/farmacología , Fluoxetina/administración & dosificación , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Interleucina-1beta/metabolismoRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Agaricus blazei Murill (AbM) is one of the main mushrooms used for medicinal purposes. The use of AbM in the preparation of teas is widespread mainly in Asian countries, while in Brazil it is used as a functional food to combat inflammatory diseases and cancer. AIM OF THE STUDY: The main focus of this study was the characterization of the chemical profile of the hydroalcoholic extract of Agaricus blazei Murill (AbE), as well as the evaluation of its cytotoxic and anti-inflammatory potential using human neutrophils. MATERIALS AND METHODS: The extract was prepared by dynamic maceration using a mixture of ethanol and water (70/30, v v-1) as solvent. The chemical profile characterization was carried out by 2D NMR and GC-MS techniques. The cytotoxicity of AbE was evaluated through studies of hemolytic potential, cell viability and membrane integrity. The anti-inflammatory activity was analyzed by a PMA-induced neutrophil degranulation assay. RESULTS: Chemical analysis of AbE revealed the presence of 28 metabolites in its composition, with mannitol as the major compound. AbE at 1-200 µg mL-1 and mannitol at 4-160 µg mL-1, showed low hemolytic and cytotoxic potential against human red blood cells and neutrophils. Furthermore, both were able to significantly reduce the release of myeloperoxidase. CONCLUSIONS: These results indicate that AbE is a promising natural product to be incorporated into pharmaceutical dosage forms intended for the adjuvant treatment of inflammatory diseases.
Asunto(s)
Agaricus , Antineoplásicos , Humanos , Neutrófilos , Cromatografía de Gases y Espectrometría de Masas , Agaricus/química , ManitolRESUMEN
Macromolecules with antioxidant properties such as polysaccharides from Agaricus blazei Murill mushroom (PAbs) are an excellent option for manufacturing wound dressings. Based on this, this study aimed to analyze preparation, physicochemical characterization, and assessment of the potential wound-healing activity of films based on sodium alginate and polyvinyl alcohol loaded with PAbs. PAbs did not significantly alter the cell viability of human neutrophils in a concentration range of 1-100 µg mL-1. The Infrared Spectroscopy (FTIR) indicates that the components present in the films (PAbs/Sodium Alginate (SA)/Polyvinyl Alcohol (PVA)) present an increase in hydrogen bonds due to the increase of hydroxyls present in the components. Thermogravimetry (TGA), Differential Scanning Calorimetry (DSC) and X-ray Diffraction (XRD) characterizations indicate a good miscibility between the components where PAbs increasing the amorphous characteristics of the films and that the addition of SA increased the mobility of the chains PVA polymers. The addition of PAbs to films significantly improves properties such as mechanical, thickness, and water vapor permeation. The morphological study evidenced good miscibility between the polymers. The wound healing evaluation indicated that F100 film presented better results from the fourth day onward compared to the other groups. It favored the formation of a thicker dermis (476.8 ± 18.99 µm), with greater collagen deposition and a significant reduction in malondialdehyde and nitrite/nitrate, markers of oxidative stress. These results indicate that PAbs is a candidate for wound dressing.
Asunto(s)
Alginatos , Alcohol Polivinílico , Humanos , Alcohol Polivinílico/química , Alginatos/química , Polisacáridos/farmacología , Cicatrización de Heridas , Vendajes , PolímerosRESUMEN
In this study, pentacyclic triterpene-loaded emulsions were stabilized by polysaccharides from Agaricus blazei Murill mushroom (PAb). The drug-excipient compatibility results by Fourier Transform Infrared Spectroscopy (FTIR) and Differential Scanning Calorimetry (DSC) showed the absence of physicochemical incompatibilities. The use of these biopolymers at 0.75 % led to obtaining emulsions with droplets smaller than 300 nm, moderate polydispersity, and ζ-potential >30 mV in modulus. The emulsions presented high encapsulation efficiency, suitable pH for topical application, and absence of macroscopic signs of instability during 45 days. Morphological analysis suggested the deposition of thin layers of PAb around the droplets. The encapsulation of pentacyclic triterpene in emulsions, stabilized by PAb, improved the cytocompatibility of this drug against PC12 and murine astrocyte cells. There was a reduction in cytotoxicity, which resulted in a lower accumulation of intracellular reactive oxygen species and maintenance of the mitochondrial transmembrane potential. Based on these results, it is estimated that PAb are promising biopolymers for the emulsions' stabilization by improving their physicochemical and biological properties.
Asunto(s)
Agaricus , Citoprotección , Ratones , Animales , Emulsiones , Polisacáridos/farmacología , Polisacáridos/química , Agaricus/química , Triterpenos PentacíclicosRESUMEN
This work aimed the development and evaluation of the wound healing activity of films based on sodium alginate, polyvinyl alcohol (PVA) and Ca2+ loaded with Agaricus blazei Murill hydroalcoholic extract (AbE). Firstly, AbE was prepared using a previously standardized methodology. The films were prepared by casting technique and cross-linked with Ca2+ using CaCl2 as cross-linking agent. The physicochemical, morphological and water vapor barrier properties of the films were analyzed and the pre-clinical efficacy was investigated against the cutaneous wound model in mice. The films showed barrier properties to water vapor promising for wound healing. AbE showed physical and chemical interactions between both polymers, noticed by Fourier transform infrared spectroscopy, X-ray diffraction, scanning electron microscopy, and thermal analysis. The delivery of AbE in alginate/PVA films enhanced the antioxidant and wound healing properties of these polymers. Consequently, a reduction of malondialdehyde levels was observed, as well as an increase of the epidermis/dermis thickness and enhancement in collagen I deposition. Thus, these formulations are promising biomaterials for wound care and tissue repairing.
Asunto(s)
Alginatos , Alcohol Polivinílico , Ratones , Animales , Alginatos/farmacología , Alginatos/química , Alcohol Polivinílico/farmacología , Alcohol Polivinílico/química , Vapor , Cicatrización de HeridasRESUMEN
The skin is the largest organ in the human body and its physical integrity must be maintained for body homeostasis and to prevent the entry of pathogenic microorganisms. Sodium alginate (SA) and polyvinyl alcohol (PVA) are two polymers widely used in films for wound dressing applications. Furthermore, blends between SA and PVA improve physical, mechanical and biological properties of the final wound healing material when compared to the individual polymers. Different drugs have been incorporated into SA/PVA-based films to improve wound healing activity. It is noteworthy that SA/PVA films can be crosslinked with Ca2+ or other agents, which improves physicochemical and biological properties. Thus, SA/PVA associations are promising for the biomedical field, as a potential alternative for wound treatment. This review focuses on the main techniques for obtaining SA/PVA films, their physical-chemical characterization, drug incorporation, and the advantages and challenges of these films for wound healing.
Asunto(s)
Alginatos , Alcohol Polivinílico , Humanos , Alcohol Polivinílico/química , Alginatos/química , Cicatrización de Heridas , Vendajes , PolímerosRESUMEN
This work aimed to evaluate the in vitro anthelmintic effect of carvone nanoemulsions on Haemonchus contortus. Three R-carvone nanoemulsions were prepared: uncoated R-carvone nanoemulsions homogenized in a sonicator (UNAlg-son) and homogenized in an ultrahomogenizer (UNAlg-ultra) and sodium alginate-coated R-carvone (CNAlg-ultra). The physicochemical characterizations of the nanoemulsions were carried out. The anthelmintic activity was evaluated using egg hatch test (EHT), larval development test (LDT) and adult worm motility test (AWMT). Changes in cuticle induced in adult H. contortus were evaluated by scanning electron microscopy (SEM). The results were subjected to analysis of variance and compared using the Tukey test (P < 0.05). The effective concentration to inhibit 50% (EC50) of egg hatching and larval development was calculated. The particle sizes were 281.1 nm (UNAlg-son), 152.7 nm (UNAlg-ultra) and 557.8 nm (CNAlg-ultra), and the zeta potentials were −15 mV (UNAlg-son), −10.8 mV (UNAlg-ultra) and −24.2 mV (CNAlg-ultra). The encapsulation efficiency was 99.84 ± 0.01%. SEM of the nanoemulsions showed an increase in size. In EHT, the EC50 values of UNAlg-son, UNAlg-ultra and CNAlg-ultra were 0.19, 0.02 and 0.17 mg mL−1, respectively. In LDT, they were 0.29, 0.31 and 0.95 mg mL−1 for UNAlg-son, UNAlg-ultra and CNAlg-ultra, respectively. The adult motility inhibition was 100% after 12 h of exposure to UNAlg-ultra and CNAlg-ultra, while for UNAlg-son, it was 79.16%. SEM showed changes in the buccal capsule and cuticular damage. It was concluded that R-carvone nanoemulsions showed antiparasitic action demonstrating promise for the control of infections caused by gastrointestinal nematodes in small ruminants.
Asunto(s)
Antihelmínticos , Hemoncosis , Haemonchus , Animales , Hemoncosis/tratamiento farmacológico , Hemoncosis/veterinaria , Hemoncosis/parasitología , Antihelmínticos/farmacología , Antihelmínticos/uso terapéutico , Monoterpenos Ciclohexánicos , Larva , Extractos Vegetales/farmacologíaRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: The use of mushrooms in medicine is quite old and the first report about the use of genus Agaricus in treatment of ulcers occurred in Byzantine period. This mushroom is widely consumed as food, tea, food supplements, as well as nutraceutical and cosmeceutical applications, being cultivated and appreciated in several countries such as Brazil, Korea, Japan and China. AIM OF THE STUDY: This study aimed to characterize the chemical profile and the potential gastroprotective effect of hydroalcoholic extract from Agaricus blazei Murill (HEAb). MATERIALS AND METHODS: The extract was chemically characterized by elemental analysis, UPLC-QTOF-MSE, Nuclear Magnetic Resonance (NMR) and high-performance liquid chromatography (HPLC) techniques to elucidate the metabolites present in the extract. The quantification of phenolic compounds and the in vitro antioxidant activities were performed and the gastroprotective effect of this extract was evaluated against ethanol-induced gastric ulcer model. HEAb was administered by gavage at 5, 25 and 50 mg kg-1 and N-acetylcysteine at 300 mg kg-1 (positive control). Furthermore, the pathways of nitric oxide (NO), Cyclic Guanylate Monophosphate (cGMP), prostaglandins (PGs) and the involvement of ATP-sensitive K+ Channels were modulated. RESULTS: Mannitol, malic acid, pyroglutamic acid, L-agaritine and L-valine were putatively identified by UPLC-QTOF-MSE in HEAb. In addition, it was possible to identify mannitol by the intense signals in the NMR spectra, being still quantified as the main compound in the extract by HPLC. The contents of total phenols and flavonoids corroborated with the good antioxidant activity of HEAb. This study observed that HEAb at 25 and 50 mg kg-1 had gastroprotection effect demonstrated by the reduction of histopathological parameters and the reduction of mastocytosis in the stomach of mice. CONCLUSIONS: In this study was possible to conclude that HEAb has gastroprotective effect related to the involvement of NO and PG pathways in the ethanol-induced gastric ulcer model in mice.