Inhibitory Effects of Flavonoids from the Stems and Leaves of Scutellaria baicalensis Georgi on Oligodendrocyte Pyroptosis Induced by Aβ1-42
Tangtang Song, Yazhen ShangIntroduction:
Alzheimer's disease (AD) is characterized not only by gray matter lesions but also by significant white matter damage and oligodendrocyte dysfunction. This study elucidates the pyroptosis-suppressive potential of Scutellaria baicalensis Georgi stem-leaf flavonoids (SSFs) in oligodendroglial lineage cells.
Methods:
We co-treated rat oligodendrocytes (OLN-93 cell line) with 7.5 μmol/L Aβ₁₋₄₂ to simultaneouslyinduce pyroptosis and SSFs. We observed cell morphology via microscopy, measured cell viability with the MTT assay, and assessed membrane damage using the LDH release assay. We then used qPCR to measure the mRNA levels of myelin-related genes (MBP, MAG, MOG) and pyroptosis-related genes (NLRP3, Caspase-1, GSDMD). We employed Western blotting to quantify the expression of pyroptosis-related proteins.Immunofluorescence was. used to localize myelin proteins whereas pyroptosis indicators and applied PI/Hoechst staining was used to evaluate cell membrane permeability within cells.
Results:
SSFs at concentrations of 15–60 mg/L significantly improved cell morphology, increased cell survival, reduced LDH release, modulated the expression of relevant genes and proteins, decreased the proportion of cells with impaired membrane integrity, and reduced the fluorescence signal of the pyroptotic execution protein GSDMD. These effects were comparable to those of the commonly used positive control, 60 mg/L Ginkgo biloba extract (GBE).
Discussion:
This study found that SSFs can alleviate Aβ-induced oligodendrocyte pyroptosis by inhibiting the NLRP3 inflammasome pathway, thereby preserving myelin function. The limitations of this study include the exclusive use of cell line models, the unclear identity of the specific active ingredients in SSFs, and the lack of verification of their blood-brain barrier penetration. Further studies, including in vivo animal experiments, active component isolation, and pharmacokinetic research, are required to evaluate its therapeutic potential for AD fully.
Conclusion:
SSFs protect oligodendrocytes against Aβ-induced injury by inhibiting the NLRP3 inflammasome pathway.