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Piericidin A is a mitochondrial complex I inhibitor.

Complex I, also known as NADH:ubiquinone oxidoreductase, catalyzes the transfer of electrons from NADH to ubiquinone as part of the respiratory chain resulting in ATP generation.

In vitro: Previous study found that piericidin A could inhibit the electron transport system at two sites. Piericidin A specifically reacted at very low concentrations at a site near the reduced NADH dehydrogenase. At high concentrations, piericidin A inhibited the succinic dehydrogenase system, and the inhibition could be partially reversed by coenzyme Q. Moreover, it was found that both the succinate and NADH oxidase system were inhibited at high levels of piericidin A [1].

In vivo: Animal study was performed to evaluate the effect of piericidin A and antagonistic effect of vitamin K3 on respiration, blood pressure and heart rate in rats. Results showed that 0.167 mg/kg of piericidin A increased the respiratory rate and the lowered blood pressure rapidly. Furthermore, vitamin K3 (10-40 mg/kg) could restore the responses to piericidin A in rats [2].

Clinical trial: Up to now, piericidin A is still in the preclinical development stage.

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