3.1 Discovery of a small molecule DACA against
MPP+-induced neuronal cells
The potential protective effects of
rosemary diterpenes, namely carnosic acid (CA), carnosol (CS), and
rosmarinol (RO), were investigated in SH-SY5Y cells. Our results
demonstrated that CS significantly enhanced the viability of
MPP+-induced SH-SY5Y cells, surpassing CA and RO (Fig.
2B). Consequently, we synthesized a carnosol derivative named DACA
through a simple structural modification of carnosol (Fig. 2C-D).
Notably, DACA exhibited superior anti- MPP+ activity
compared to carnosol alone without any apparent cytotoxicity towards
cells (Fig. 2E). To further validate the neuroprotective effect of DACA,
we used MPP+ to stimulate primary neurons to evaluate
its impact. Our findings revealed that DACA effectively inhibited
MPP+-induced injury in primary neurons while
exhibiting no influence on primary neuron survival when administered
alone (Fig. 2E). Collectively, these findings highlight DACA as a
valuable small molecule capable of safeguarding against
MPP+- induced neuronal cell injury.