As a well-known
analgesic drug,
acetaminophen (
APAP) is commonly used to relieve
pain for patients with chronic painful diseases. Our previous study has shown that long-term ingestion of
APAP caused
liver fibrosis in mice. This study further investigated the critical role of nuclear factor erythroid 2-related factor 2 (Nrf2) in regulating
APAP-induced
liver fibrosis in mice and the anti-fibrotic effect of natural compound
andrographolide (Andro). Our results showed that hepatic
collagen deposition and hepatic stellate cells (HSCs) activation induced by
APAP were more serious in Nrf2 knock-out mice than in normal wild-type mice. Andro reduced HSCs activation in vitro, and also decreased hepatic
collagen deposition and HSCs activation induced by
APAP in mice. Andro alleviated liver oxidative stress injury induced by
APAP in mice and reduced cellular formation of
reactive oxygen species (ROS) in HSCs. Andro enhanced Nrf2 nuclear translocation and increased the expression of Nrf2 downstream
antioxidant genes both in vitro and in vivo. Furthermore, the Andro-provided protection against
APAP-induced
liver fibrosis was diminished in Nrf2 knock-out mice. In summary, Nrf2 is critically involved in preventing
liver fibrosis induced by long-term administration of
APAP in mice, and Andro alleviates
APAP-induced
liver fibrosis by attenuating liver oxidative stress injury via inducing Nrf2 activation. This study points out the potential application of Andro in the treatment of
liver fibrosis in clinic.