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.