Vascular disease remains the leading cause of death and disability, the etiology of which often involves atherosclerosis. The current treatment of atherosclerosis by pharmacotherapy has limited therapeutic efficacy. Here we report a biomimetic drug delivery system derived from macrophage membrane coated ROS-responsive nanoparticles (NPs). The macrophage membrane not only avoids the clearance of NPs from the reticuloendothelial system, but also leads NPs to the inflammatory tissues, where the ROS-responsiveness of NPs enables specific payload release. Moreover, the macrophage membrane sequesters proinflammatory cytokines to suppress local inflammation. The synergistic effects of pharmacotherapy and inflammatory cytokines sequestration from such a biomimetic drug delivery system lead to improved therapeutic efficacy in atherosclerosis. Comparison to macrophage internalized with ROS-responsive NPs, as a live-cell based drug delivery system for treatment of atherosclerosis, suggests that cell membrane coated drug delivery approach is likely more suitable for dealing with an inflammatory disease than the live-cell approach.
Cucurbit [7]uril (CB [7]) was found in vitro to sequester the neurotoxins MPTP (N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) and MPP + (N-methyl-4-phenylpyridine). The CB [7]/neurotoxin host−guest complexes were studied in detail with 1 H NMR, electrospray ionization mass spectrometry, UV− visible spectroscopic titration, and molecular modeling by density functional theory. The results supported the macrocyclic encapsulation of MPTP and MPP + , respectively, by CB [7] in aqueous solutions with relatively strong affinities and 1:1 host− guest binding stoichiometries in both cases. More importantly, the progression of MPTP/MPP + induced neurodegeneration (often referred to as a Parkinson's disease model) was observed to be strongly inhibited in vivo by the synthetic CB [7] receptor, as shown in zebrafish models. These results show that a supramolecular approach could lead to a new preventive and/or therapeutic strategy for counteracting the deleterious effects of some neurotoxins leading to neurodegeneration.
SUMMARYObjective: Epilepsy is a serious neural disease that affects around 50 million people all over the world. Although for the majority patients with epilepsy, seizures are well controlled by currently available antiepileptic drugs (AEDs), there are still >30% of patients suffered from medically refractory epilepsy and approximately 30-40% of all epileptic patients affected by numerous side effects and seizure resistance to the current AEDs. Therefore, many researchers try to develop novel approaches to treat epilepsy, for example, to discover new antiepileptic constituents from herbal medicines. Although there are already several reviews on phytotherapy in epilepsy, most of them placed emphasis on the plant crude extracts or their isolated fractions, not pure active compounds derived from herbal medicines. This article aims to review components in herbal medicines that have shown antiepileptic or anticonvulsant properties. Methods: We searched online databases and identified articles using the preset searching syntax and inclusion criteria. The active medicinal compounds that have shown anticonvulsant or antiepileptic activity were included and classified according to structural types. Results: We have reviewed herein the active constituents including alkaloids, flavonoids, terpenoids, saponins, and coumarins. The screening models, the seizures-inducing factors and response, the effective dose, the potential mechanisms, as well as the structure-activity relationships in some of these active components have also been discussed. Significance: The in vitro and in vivo experimental data reviewed in this paper would supply the basic science evidence for research and development of novel AEDs from medicinal plants.
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