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1.
Nat Commun ; 11(1): 3815, 2020 07 27.
Article in English | MEDLINE | ID: mdl-32719450

ABSTRACT

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

2.
Nat Commun ; 10(1): 1604, 2019 04 08.
Article in English | MEDLINE | ID: mdl-30962431

ABSTRACT

Self-assembling natural drug hydrogels formed without structural modification and able to act as carriers are of interest for biomedical applications. A lack of knowledge about natural drug gels limits there current application. Here, we report on rhein, a herbal natural product, which is directly self-assembled into hydrogels through noncovalent interactions. This hydrogel shows excellent stability, sustained release and reversible stimuli-responses. The hydrogel consists of a three-dimensional nanofiber network that prevents premature degradation. Moreover, it easily enters cells and binds to toll-like receptor 4. This enables rhein hydrogels to significantly dephosphorylate IκBα, inhibiting the nuclear translocation of p65 at the NFκB signalling pathway in lipopolysaccharide-induced BV2 microglia. Subsequently, rhein hydrogels alleviate neuroinflammation with a long-lasting effect and little cytotoxicity compared to the equivalent free-drug in vitro. This study highlights a direct self-assembly hydrogel from natural small molecule as a promising neuroinflammatory therapy.


Subject(s)
Anthraquinones/administration & dosage , Anti-Inflammatory Agents/administration & dosage , Drug Carriers/chemistry , Inflammation/drug therapy , Microglia/drug effects , Animals , Anthraquinones/chemistry , Anthraquinones/pharmacokinetics , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/pharmacokinetics , Cell Line , Delayed-Action Preparations/administration & dosage , Delayed-Action Preparations/chemistry , Delayed-Action Preparations/pharmacokinetics , Drug Carriers/administration & dosage , Drug Carriers/pharmacokinetics , Drug Evaluation, Preclinical , Drug Liberation , Hydrogels/administration & dosage , Hydrogels/chemistry , Hydrogels/pharmacokinetics , Inflammation/immunology , Inflammation/pathology , Lipopolysaccharides/immunology , Mice , Microglia/immunology , Microglia/pathology , Microscopy, Electron, Scanning , NF-KappaB Inhibitor alpha/immunology , NF-KappaB Inhibitor alpha/metabolism , Nanofibers/administration & dosage , Nanofibers/chemistry , Nanofibers/ultrastructure , Phosphorylation/drug effects , Phosphorylation/immunology , Phytochemicals/administration & dosage , Phytochemicals/chemistry , Phytochemicals/pharmacokinetics , Rheum/chemistry , Signal Transduction/drug effects , Signal Transduction/immunology , Toll-Like Receptor 4/metabolism , Transcription Factor RelA/immunology , Transcription Factor RelA/metabolism
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