Piericidin A is a natural mitochondrial NADH- ubiquinone oxidoreductase (complex I) inhibitor. Piericidin A interferes with the electron transfer chain by inhibiting the activity of NADH- ubiquinone reductase, thus inhibiting mitochondrial respiration, which shows a certain neurotoxic effect. Piericidin A has potential quorum sensing inhibitory activity, antibacterial, antitumor and insecticidal activities.

ACHN cells:1.6 μM, HL-60 cells:82.1 μM, HeLa cells:84.9 μM, HT-29 cells:6.4 nM, HepG2 cells:233.97 μM, HK-2 cells:> 100 μM, HEK293 cells:228.96 μM, OS-RC-2 cells:5.2 μM, L929 cells:0.43 nM, SW480:82.1 μM

In cell-free experiments, the inhibitory effect of Piericidin A on mitochondrial complex I was about 2 times lower than that of annonacin. In cultured neurons, Piericidin A strongly induces the redistribution of phosphorylated tau from dendrites to cell bodies, and induces cell death [1].
Piericidin A inhibited the activity of Tn5B1-4 cells in a time-and concentration-dependent manner, with an IC50 of 0.061 μM, while Piericidin A slightly inhibited the activity of HepG2 and Hek293 cells, with IC50 values of 233.97 μM and 228.96 μM, respectively. Piericidin A induced apoptosis of Tn5B1-4 cells, which occurred simultaneously with the decrease of mitochondrial membrane potential [3].

Piericidin A (0.5 mg/kg/d； Administered by osmotic micropump for 28 days) significantly increased the number of phosphorylated tau immunoreactive cells in the cerebral cortex of P301S+/+ mice. Piericidin A only increased the level of pathological phosphorylated tau in P301S+/+ mice. The synaptic density of P301S+/+ mice treated with Piericidin A decreased. Exposure to Piericidin A will aggravate the pathological process of tau determined by genes [1].