Fig. 2. Discovery of a
small molecule DACA against MPP+-induced neuronal
cells. (A) Chemical structure of Carnosic acid (CA), Rosmarinol (RO),
Carnosol (CS). (B) Effects of CA, RO and CS and MPP+on SH-SY5Y cells (n = 5 per group). (C) Chemical structure of DACA. (D)
The chemical equation for preparing DACA. (E) Effects of different
concentrations of DACA on the viability of SH-SY5Y cells and primary
neurons (n = 5 per group). (F) Effects of DACA on the viability of
MPP+-treated
SH-SY5Y cells and primary neurons (n
= 5 per group). Data shown are mean ± SEM; #p
< 0.05, ##p < 0.01 vs. control;
*p < 0.05, **p < 0.01 vs. MPP+.
NS. not significant.
3.2 DACA alleviates motor
dysfunction in MPTP-induced PD mice
The MPTP-induced model serves as a well-established experimental
paradigm for investigating molecules associated with Parkinson’s
disease[27]. To explore the impact of DACA on
motor dysfunction and behavioral changes, we conducted a series of
fundamental behavioral experiments, including the open field test and
pole climbing test. As depicted in Fig. 3B-C, compared to the control
group, MPTP treatment significantly decreased the total distance
traveled by mice within the open field box. However, this reduction was
ameliorated in all DACA dosage groups. Similarly, MPTP-treated mice
exhibited reduced dwell time in the central region and a notable
increase in corner time. In contrast, DACA treatment effectively
enhanced dwell time in the central region while reducing corner time
(Fig. 3B-C). In the climbing pole
test, the MPTP-treated group exhibited a significant increase time in
falling to the floor and turning head compared with the control group,
whereas mice treated with DACA showed a decrease in these parameters
(Fig. 3C). These data suggest that DACA mitigates MPTP-induced
impairments in muscle control and motor function in mice.