Directed self-assembly of herbal small molecules into sustained release hydrogels for treating neural inflammation.

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  • Additional Information
    • Source:
      Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE
    • Publication Information:
      Original Publication: [London] : Nature Pub. Group
    • Subject Terms:
      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
    • 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.
    • Comments:
      Erratum in: Nat Commun. 2020 Jul 27;11(1):3815. (PMID: 32719450)
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    • Accession Number:
      0 (Anthraquinones)
      0 (Anti-Inflammatory Agents)
      0 (Delayed-Action Preparations)
      0 (Drug Carriers)
      0 (Hydrogels)
      0 (Lipopolysaccharides)
      0 (Nfkbia protein, mouse)
      0 (Phytochemicals)
      0 (Rela protein, mouse)
      0 (Tlr4 protein, mouse)
      0 (Toll-Like Receptor 4)
      0 (Transcription Factor RelA)
      139874-52-5 (NF-KappaB Inhibitor alpha)
      YM64C2P6UX (rhein)
    • Publication Date:
      Date Created: 20190410 Date Completed: 20190610 Latest Revision: 20200728
    • Publication Date:
      20240829
    • Accession Number:
      PMC6453967
    • Accession Number:
      10.1038/s41467-019-09601-3
    • Accession Number:
      30962431