Open AccessBaicalin Alleviates Age-Related Macular Degeneration via <b><i>miR-223/NLRP3</i></b>-Regulated Pyroptosis
Author(s) -
Hong-Jing Sun,
Xiuming Jin,
Jia Xu,
Qing Xiao
Publication year - 2019
Publication title -
pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.51
H-Index - 59
eISSN - 1423-0313
pISSN - 0031-7012
DOI - 10.1159/000502614
Subject(s) - baicalin , pyroptosis , western blot , viability assay , chemistry , downregulation and upregulation , gene knockdown , pharmacology , apoptosis , microbiology and biotechnology , medicine , programmed cell death , biology , biochemistry , high performance liquid chromatography , chromatography , gene
Background: Age-related macular degeneration (AMD), a major eye degenerative disease, ultimately causes irreversible vision loss. Baicalin was identified to attenuate laser-induced chorodial neovascularization, indicating a therapeutic role in AMD. However, the exact mechanisms for baicalin in AMD remain unknown. Methods: MTT assay was performed to access the suitable concentration of baicalin or Aβ for treating ARPE-19 cells. CCK-8, morphology, and flow cytometry analysis were performed to evaluate cell viability and pyroptosis of baicalin in Aβ-envoked ARPE-19 cells. Quantitative real-time polymerase chain reaction and western blot analysis were subjected to measure the correlation between miR-223 and NLRP3. Luciferase reporter assay was performed to determine their direct relationship. Western blot analysis was subjected to determine pyroptosis-related proteins. Results: Baicalin inhibited Aβ-envoked pyroptosis in ARPE-19 cells. Mechanistically, baicalin significantly induced upregulation of miR-223 and downregulation of NLRP3, thus suppressing pyroptosis triggered by NLRP3 inammasome signaling, yet such beneficial effects were reversed by miR-223 knockdown. Additionally, MCC950, a NLRP3 inhibitor, restored anti-pyroptosis activity of baicalin under miR-223 silencing. Conclusion: Baicalin alleviates intracellular pyroptosis and viability damage resulted from Aβ inducement in human retinal pigment epithelium cells via negative crosstalk of miR-223/NLRP3 inammasome signaling, indicating that baicalin may be considered as a potential candidate for AMD therapy.