Cyclo(-Phe-Phe) alleviates chick embryo liver injury via activating the Nrf2 pathway.
Qiong-Yi ZhangShao-Cong HanRong-Ping HuangMan-Ya JiangChang-Yu YanXi-You LiYu-Jiao ZhanXiao-Min LiYi-Fang LiHiroshi KuriharaRui-Rong TanWei-Xi LiRong-Rong HePublished in: Food & function (2022)
Excessive reactive oxygen species (ROS) accumulation is involved in the pathogenesis of liver fibrosis and damage, specifically in the developing embryo that is extremely sensitive to oxidative stress. Herein, a liver injury model in chick embryo was established by using 2,2-azobis (2-amidinopropane) dihydrochloride (AAPH), which was used to investigate the effect of cyclo(-Phe-Phe) (CPP), a natural dipeptide found in foods and beverages. The results showed that CPP significantly alleviated AAPH-induced liver pathological damage, hepatic dysfunction and inhibited the excessive production of ROS in both chick embryo liver and HepG2 cells. Additionally, CPP increased the antioxidative activity of glutathione peroxidase (GPx) and superoxide dismutase (SOD), as well as elevated the level of glutathione (GSH), suggesting that CPP combating liver injury probably depends on its antioxidant capability. Mechanistically, CPP upregulated the mRNA and protein expression of heme oxyense-1 (HO-1) and NADPH quinone oxidoreductase 1 (NQO1) in vivo and in vitro , along with promoting the translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) while inhibiting its degradation through binding with Kelch-like ECH-associated protein 1 (Keap1). In conclusion, this study proposes a potential peptide drug for the treatment of hepatic damage induced by oxidative stress and also unravels its mechanism of action.
Keyphrases
- oxidative stress
- liver injury
- drug induced
- reactive oxygen species
- diabetic rats
- dna damage
- nuclear factor
- liver fibrosis
- pregnancy outcomes
- ischemia reperfusion injury
- induced apoptosis
- signaling pathway
- cell death
- toll like receptor
- hydrogen peroxide
- weight gain
- adverse drug
- pi k akt
- mouse model
- pregnant women
- anti inflammatory
- emergency department
- inflammatory response
- high glucose
- heat shock
- body mass index
- physical activity
- small molecule
- nitric oxide
- climate change
- cell proliferation