The Combination of β-Asarone and Icariin Inhibits Amyloid-β and Reverses Cognitive Deficits by Promoting Mitophagy in Models of Alzheimer’s Disease

Figure 6

Mitophagy induces by combination drug inhibits amyloid-β and reverses cognitive deficits. APP/PS1 mice were treated as groups by daily gavage for 4 weeks, behavioural tests were performed, and brains and serum were subjected to histological and molecular analyses. (a) Morris water maze, step-down, and step-through were tested after administration (each group, , , and ). Water maze performance was analysed by the amount of time spent in the target quadrant (sec). APP/PS1 mice showed significant memory loss in all three tests. Time spent target quadrant was decreased after the combination and A3. (b) The analytical performance of the MSD Aβ38, Aβ40, and Aβ42 in serum, hippocampal, and prefrontal cortex tissue assays in terms of parallelism, sensitivity, accuracy, precision, lot-to-lot variability, selectivity, and freeze/thaw stability was assessed according to published guidelines ( per group). Aβ38 in mouse hippocampus and PFC was not detected, and Aβ40 and Aβ42 revealed a significant trend in AD groups. Autophagy activator A3 drug can inhibit the expression of Aβ40 and Aβ42. (c) BACE1, APP, LC3 I/II, and PINK1 levels in hippocampal tissues with WB. (d) Quantification of protein expression levels between each group. (e) IF assay of BACE1, APP, LC3 I/II, and PINK1 was detected after the treatment (scale bar 100 μm and magnification 400x) in PC12 cells. Cy3-DyLight marker protein expression, DAPI marker cell nucleus, also with a merge paper. Scale bar 100 μm. (f) Quantification of protein expression levels in cells. The experiments were repeated twice independently with similar results. Compared with the control group, , , and ; compared with AD, ^#, ^##, and ^###; one-away ANOVA.

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