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Andrographolide activates the Wnt pathway and modulates the APP processing by direct inhibiton of GSK3β
Author(s) -
Tapia Cheril Cecilia,
Mejías Cristóbal,
Bustamante Hianara,
Burgos Patricia,
Inestrosa Nibaldo C
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.835.11
Subject(s) - andrographolide , andrographis paniculata , wnt signaling pathway , chemistry , microbiology and biotechnology , signal transduction , lrp5 , receptor , pharmacology , biochemistry , biology , medicine , alternative medicine , pathology
Objectives We carry out a detailed analysis of the effect of Andrographolide (ANDRO), the major component of Andrographis paniculata, on the activation of Wnt signaling and APP processing. Methods Human H4 neuroglioma cells stably expressing APP695 and slices from wild‐type mice were incubated with ANDRO. The samples were used for biochemical analysis. Results ANDRO modulates the Wnt/β‐catenin signaling components increasing the levels of the β‐catenin by inactivation of GSK‐3β and inducing the transcription of Wnt target genes. ANDRO acts downstream from the ligand‐receptor binding, by direct inhibition of GSK3β. Finally, ANDRO seems to stimulate non‐amyloidogenic proteolytic cleavage of APP, leading to a significant increase in C83 levels, a product of α‐secretase. Conclusions We conclude that ANDRO activated Wnt pathway modulating the non‐amyloidogenic APP processing pathway by a mechanism that target inhibition of GSK3β.