RESUMEN
Recent preclinical studies have shown that resveratrol (RSV), is a promising remedy for osteoporosis owing to its estrogenic, anti-inflammatory, and antioxidant properties. However, RSV has met limited success due to its poor oral bioavailability and inefficient systemic delivery. In this study, we prepared the inclusion complex of RSV with sulfo-butyl ether ß-cyclodextrin (SBE-ß-CD) to enhance the aqueous solubility of RSV. The in-silico docking studies and Physico-chemical characterization assays were performed to understand the interaction of RSV inside the SBE-ß-CD cavity. The in vivo safety assessment of RSV-SBE-ß-CD inclusion complex (R-CDIC) was performed in healthy Wistar rats. The efficacy of the inclusion complex against postmenopausal osteoporosis was further investigated in ovariectomized (OVX) rat model. The alteration in the bone micro-architectural structure was evaluated by microcomputed tomographic scanning, serum biochemical estimations, biomechanical strength and histopathological investigation. Administration of RSV-SBE-ß-CD inclusion complex was found to be safe and significantly improved micro-architectural deterioration induced by estrogen withdrawal. Results of bone morphometry and biomechanics study further emboldened the efficacy claim of the RSV-SBE-ß-CD complex. Thus, the present study demonstrated the efficacy of the RSV-SBE-ß-CD inclusion complex for treating osteolytic degradation in osteoporosis.
Asunto(s)
Antiinflamatorios/administración & dosificación , Osteoporosis Posmenopáusica/tratamiento farmacológico , Resveratrol/administración & dosificación , beta-Ciclodextrinas/química , Animales , Antiinflamatorios/química , Antiinflamatorios/farmacología , Disponibilidad Biológica , Modelos Animales de Enfermedad , Excipientes/química , Femenino , Humanos , Simulación del Acoplamiento Molecular , Osteoporosis Posmenopáusica/diagnóstico por imagen , Ratas , Ratas Wistar , Resveratrol/química , Resveratrol/farmacología , Solubilidad , Microtomografía por Rayos XRESUMEN
BACKGROUND: The central nervous system (CNS) known to regulate the physiological conditions of human body, also itself gets dynamically regulated by both the physiological as well as pathological conditions of the body. These conditions get changed quite often, and often involve changes introduced into the gut microbiota which, as studies are revealing, directly modulate the CNS via a crosstalk. This cross-talk between the gut microbiota and CNS, i.e., the gut-brain axis (GBA), plays a major role in the pathogenesis of many neurodegenerative disorders such as Parkinson's disease (PD), Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS) and Huntington's disease (HD). OBJECTIVE: We aim to discuss how gut microbiota, through GBA, regulate neurodegenerative disorders such as PD, AD, ALS, MS and HD. METHODS: In this review, we have discussed the present understanding of the role played by the gut microbiota in neurodegenerative disorders and emphasized the probable therapeutic approaches being explored to treat them. RESULTS: In the first part, we introduce the GBA and its relevance, followed by the changes occurring in the GBA during neurodegenerative disorders and then further discuss its role in the pathogenesis of these diseases. Finally, we discuss its applications in possible therapeutics of these diseases and the current research improvements being made to better investigate this interaction. CONCLUSION: We concluded that alterations in the intestinal microbiota modulate various activities that could potentially lead to CNS disorders through interactions via the GBA.
Asunto(s)
Encéfalo/fisiología , Microbioma Gastrointestinal/fisiología , Enfermedades Neurodegenerativas/microbiología , Animales , Encéfalo/efectos de los fármacos , Encéfalo/patología , Microbioma Gastrointestinal/efectos de los fármacos , Humanos , Enfermedades Neurodegenerativas/tratamiento farmacológico , Enfermedades Neurodegenerativas/patología , Fármacos Neuroprotectores/química , Fármacos Neuroprotectores/farmacologíaRESUMEN
A new photoactive organic crystal, 1-methyl piperazinium 4-nitrophenolate-4-nitrophenol monohydrate (MP4NPM) has been synthesised at 35 °C. Good quality single crystals of MP4NPM have successfully been grown by slow evaporation solution growth technique. Single crystal X-ray diffraction analysis shows that MP4NPM belongs to monoclinic crystal system with space group P21/n. The molecular structure was further confirmed by modern spectroscopic techniques like FT-NMR (both 1D and 2D), FT-IR, UV-Vis-NIR and fluorescence. The UV-Vis-NIR spectrum was performed to understand the range of optical transparency and the results showed its suitability for nonlinear optical applications. Fluorescence emission revealed that MP4NPM can serve as a photo active material. Thermal properties of MP4NPM were investigated using simultaneous TG-DSC analysis. Frequency and temperature dependent dielectric properties were studied in the frequency range 500 Hz-5 MHz and 40-50 °C, respectively. Vicker's microhardness measurements revealed that MP4NPM belongs to the category of soft material. Kurtz and Perry powder technique shows that MP4NPM has SHG efficiency 0.89 times that of potassium dihydrogen phosphate (KDP).