Abstract:

The cytotoxicity of four types of flavonoid monomers, namely chlorogenic acid, ferulic acid, orientin and
isoorientin on Chinese hamster ovary (CHO) cells was detected and compared by CCK-8 test and the IC50 values were
calculated by Exact Probability. The mitochondrial membrane potential, the production of ATP and the release of cytochrome
C were used as the parameters to indicate early cellular damage. The results showed that IC50 of chlorogenic acid, ferulic
acid, orientin and isoorientin was 2 726.11, 1 680.28, 1 889.15 and 2 358.56 μmol/L, respectively. At experimental doses
of IC50, 1/2 IC50, 1/4 IC50, and 1/8 IC50 for these four monomers, the change of mitochondrial membrane potential was in
a dose-dependent manner. Meanwhile, ferulic acid resulted in the largest decease in mitochondrial membrane potential,
followed by chlorogenic acid, orientin and isoorientin. The production of ATP was negatively correlated with the dose of
flavonoids, which was inhibited by ferulic acid, orientin, chlorogenic acid and isoorientin in this decreasing order. In the case
of cytochrome C release, the decreasing order was ferulic acid, orientin, isoorientin and chlorogenic acid. In summary, all
the four flavonoids can result in mitochondrial damage at higher or lower levels. Ferulic acid has the highest mitochondrial
toxicity, followed by orientin, isoorientin and chlorogenic acid. The change of mitochondrial function may be considered as
an index of early cellular damage.

Key words: cytochrome C, mitochondrial membrane potential, adenosine triphosphate, mitochondrial damage, chlorogenic acid, ferulic acid, orientin, isoorientin