PMC

Chemical structure of APAU.

sEH inhibitors APAU mediated neuroprotection against ROT induced toxicity.

Effect of APAU (2.5 μM/ml) on ROT (400 nM) induced protein oxidation, as determined by estimation of protein carbonyls by oxyblot. The data represent mean ± SEM of three independent experiments. ^#p < 0.05 versus Control group; *p < 0.05 versus ROT group and ^$p < 0.05 versus Control group.

Effect of APAU (2.5 μM/ml) on ROT (400 nM) induced altered mitochondrial complex I activity in N27 cell model. The data represent mean ± SEM of three independent experiments. #p < 0.05 versus control group and *p < 0.05 versus rotenone group.

Effect of APAU (2.5 μM/ml) on ROT (400 nM) induced altered expression of redox genes (SOD, CAT), and inflammatory markers (COX-1 and 2, IL-6) assessed by RT-PCR. The data represent mean ± SEM of three independent experiments. #p < 0.05 versus Control group; *p < 0.05 versus ROT group and ^$p < 0.05 versus Control group.

(a) Dose dependent effect of ROT (1–500 nM) on N27 cell viability assessed by MTT assay. The data represent mean ± SEM of three independent experiments. *p < 0.05 versus Control group. (b) Protective effect of APAU (2.5–10 μM/ml) against ROT (400 nM) induced cytotoxicity assessed by MTT assay. The data represent mean ± SEM of three independent experiments. #p < 0.05 versus Control group and *p < 0.05 versus ROT group. (c) Protective effect of APAU (2.5–10 μM/ml) against ROT (400 nM) induced LDH leakage. The data represent mean ± SEM of three independent experiments. #p < 0.05 versus Control group and *p < 0.05 versus ROT group.

(a-c): Effect of APAU (2.5 μM/ml) on ROT (400 nM) induced alterations in apoptotic marker proteins - phospho c-jun, phospho JNK and caspase 3 analyzed by using western blot. Quantification of the individual bands in the blot is represented by bar graphs below the blots. The data represent mean ± SEM of three independent experiments. #p < 0.05 versus control group; *p < 0.05 versus ROT group and ^$p < 0.05 versus Control group.

a, b, c, and d: Protective effect of APAU on ROT-induced mortality and locomotor deficits in the Drosophila model of PD. Dose dependent lethality response expressed as percent mortality among adult male Drosophila exposed to various concentration of ROT (10–1000 μM) and APAU (50–1000 μM) is shown in Fig. 7a, and b; c shows the % mortality among the flies pre-treated with APAU (50–100 μM) for 5 days, followed by co-treated with both APAU and ROT for 7 days. Fig. 7d shows the improvement in the locomotor deficits by APAU (50–100 μM) as determined by negative geotaxis assay. The data represented in percentage, where n=2. Analyzed by using one way analysis of variance followed by Bonferroni post test.