| Description: |
Corynoxine B, a natural autophagy inducer, restores the deficient cytosolic translocation of HMGB1 and autophagy in cells overexpressing SNCA, which may be attributed to its ability to block SNCA-HMGB1 interaction. Corynoxine B exhibits prolongation of the thiopental-induced hypnosis on oral administration in mice. |
| Targets: |
PLK | ERK | Beta Amyloid | Autophagy | MAPK | HMGB1 |
| In vitro: |
| Autophagy. 2014 Jan;10(1):144-54. | | HMGB1 is involved in autophagy inhibition caused by SNCA/α-synuclein overexpression: a process modulated by the natural autophagy inducer corynoxine B.[Pubmed: 24178442 ] | SNCA/α-synuclein and its rare mutations are considered as the culprit proteins in Parkinson disease (PD). Wild-type (WT) SNCA has been shown to impair macroautophagy in mammalian cells and in transgenic mice.
METHODS AND RESULTS:
In this study, we monitored the dynamic changes in autophagy process and confirmed that overexpression of both WT and SNCA(A53T) inhibits autophagy in PC12 cells in a time-dependent manner. Furthermore, we showed that SNCA binds to both cytosolic and nuclear high mobility group box 1 (HMGB1), impairs the cytosolic translocation of HMGB1, blocks HMGB1-BECN1 binding, and strengthens BECN1-BCL2 binding. Deregulation of these molecular events by SNCA overexpression leads to autophagy inhibition. Overexpression of BECN1 restores autophagy and promotes the clearance of SNCA. siRNA knockdown of Hmgb1 inhibits basal autophagy and abolishes the inhibitory effect of SNCA on autophagy while overexpression of HMGB1 restores autophagy.
CONCLUSIONS:
Corynoxine B, a natural autophagy inducer, restores the deficient cytosolic translocation of HMGB1 and autophagy in cells overexpressing SNCA, which may be attributed to its ability to block SNCA-HMGB1 interaction. Based on these findings, we propose that SNCA-induced impairment of autophagy occurs, in part, through HMGB1, which may provide a potential therapeutic target for PD. |
|
| In vivo: |
| Phytomedicine. 1998 Apr;5(2):83-6. | | Effect of oxindole alkaloids from the hooks of Uncaria macrophylla on thiopental-induced hypnosis.[Pubmed: 23195758 ] |
METHODS AND RESULTS:
Four tetracyclic oxindole alkaloids, rhynchophylline, isorhynchophylline, corynoxine and Corynoxine B were isolated from the hooks of Uncaria macrophylla Wall. (Rubiaceae), that is a dominant plant widely distributed in Yunnan province.
CONCLUSIONS:
These compounds exhibited prolongation of the thiopental-induced hypnosis on oral administration in mice. |
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