Rutaecarpine, an indolopyridoquinazolinone
alkaloid isolated from the unripe fruit of Evodia rutaecarpa, is used to treat
hypertension,
postpartum hemorrhage,
dysentery, and
amenorrhea as a
traditional medicine in Asia. We investigated the effect of
rutaecarpine on
acetaminophen-induced hepatotoxicity in mice.
Rutaecarpine was administered orally daily for seven consecutive days, followed by
intraperitoneal injection of
acetaminophen in mice on day seven to induce hepatotoxicity.
Rutaecarpine pretreatment significantly decreased
acetaminophen-induced serum
alanine aminotransferase (ALT)/
aspartate aminotransferase (AST) activities and hepatic
malondialdehyde content and prevented
acetaminophen-induced hepatic
glutathione depletion. Furthermore,
CYP2E1 expression was decreased by
rutaecarpine pretreatment in a dose-dependent manner.
Rutaecarpine pretreatment inhibited
acetaminophen-induced expression of inflammatory
cytokines by inhibiting NF-κB activation by JNK1/2. Also,
rutaecarpine pretreatment promoted Nrf2-mediated activation of the
antioxidant enzymes GCLC, HO-1, and NQO1. This indicates that the protective effect of
rutaecarpine during
acetaminophen-induced acute liver injury is mediated by the activation of
antioxidant enzymes. Therefore,
rutaecarpine has a protective effect of
APAP-induced liver damage.