Intelligent lesion blood–brain barrier targeting nano-missiles for Alzheimer's disease treatment by anti-neuroinflammation and neuroprotection

The treatment of Alzheimer's disease(AD)is one of the most difficult challenges in neurodegenerative diseases due to the insufficient blood‒brain barrier(BBB)permeability and unsatisfactory intra-brain distribution of drugs.Therefore,we established an ibuprofen and FK506 encapsulated drug co-delivery system(Ibu&FK@RNPs),which can target the receptor of advanced glycation endproducts(RAGE)and response to the high level of reactive oxygen species(ROS)in AD.RAGE is highly and specifically expressed on the lesion neurovascular unit of AD,this property helps to improve targeting specificity of the system and reduce unselective distribution in normal brain.Meanwhile,these two drugs can be specifically released in astrocytes of AD lesion in response to high levels of ROS.As a result,the cognition of AD mice was significantly improved and the quantity of Aβplaques was decreased.Neurotoxicity was also alleviated with structural regeneration and functional recovery of neurons.Besides,the neuroinflammation dominated by NF-κB pathway was significantly inhibited with decreased NF-κB and IL-1βin the brain.Overall,Ibu&FK@RNPs can efficiently and successively target diseased BBB and astrocytes in AD lesion.Thus it significantly enhances intracephalic accumulation of drugs and efficiently treats AD by anti-neuroinflammation and neuroprotection.

Chemical constituents from leaves of Jatropha curcas

Objective:To investigate the chemical constituents from the leaves of Jatropha curcas and evaluate their inhibition on lipopolysaccharide(LPS)-activated BV-2 microglia cells.Methods:The n-BuOH extract of the leaves of J.curcas was isolated by macroporous adsorption resin,silica gel,ODS,column chromatography and semi-preparative HPLC.The structures of the compounds were identified by MS,NMR,ECD,and other spectroscopic methods.In addition,anti-neuroinflammatory effects of isolated compounds were evaluated by measuring the production of nitric oxide(NO)in overactivated BV-2 cells.Results:Seventeen compounds,including(7R,8S)-crataegifin A-4-O-β-D-glucopyranoside(1),(8R,8’R)-arctigenin(2),arctigenin-4’-O-β-D-glucopyranoside(3),(-)-syringaresinol(4),syringaresinol-4’-O-β-Dglucopyranoside(5),(-)-pinoresinol(6),pinoresinol-4’-O-β-D-glucopyranoside(7),buddlenol D(8),(2R,3R)-dihydroquercetin(9),(2S,3S)-epicatechin(10),(2R,3S)-catechin(11),isovitexin(12),naringenin-7-O-β-D-glucopyranoside(13),chamaejasmin(14),neochamaejasmin B(15),isoneochamaejasmin A(16),and tomentin-5-O-β-D-glucopyranoside(17)were isolated and identified.Compounds 2,4and 8 significantly inhibited the release of NO in BV-2 microglia activated by LPS,with IC50values of18.34,29.33 and 26.30μmol/L,respectively.Conclusion:Compound 1 is a novel compound,and compounds 2,3,8,14–17 are isolated from Jatropha genus for the first time.In addition,the lignans significantly inhibited NO release and the inhibitory activity was decreased after glycosylation.

Diterpenoids from the aerial parts of Leonurus macranthus

Four new diterpenoids including one cis clerodane-type(1) and three highly oxygenated labdane-type diterpenes(2–4) were isolated from the aerial parts of Leonurus macranthus. Their structures were elucidated on the basis of spectroscopic data(NMR, UV, IR, and MS). Compound 1 represents the first example of cis clerodane-type diterpene in the plants of Leonurus genus. Compounds 1 and 4 exhibited weak inhibition of nitric oxide production in lipopolysaccharide-stimulated BV-2 microglial cells with IC_(50) values of 35.8 ± 3.6 mmol/L and 48.6 ± 4.8 mmol/L,