Chlorogenic acid promotes the Nrf2/HO-1 anti-oxidative pathway by activating p21Waf1/Cip1 to resist dexamethasone-induced apoptosis in osteoblastic cells.

Chlorogenic acid promotes the Nrf2/HO-1 anti-oxidative pathway by activating p21Waf1/Cip1 to resist dexamethasone-induced apoptosis in osteoblastic cells. Free Radic Biol Med. 2019 Apr 17;: Authors: Han D, Gu X, Gao J, Wang Z, Liu G, Barkema HW, Han B Abstract In a previous study, p21Waf1/Cip1 (p21) promoted activation of the nuclear factor E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway, which has an important role in regulating apoptosis triggered by oxidative stress and inhibiting development of osteoporosis. Chlorogenic acid (CGA) has a strong protective effect on osteoporosis, closely related to activating the Nrf2/HO-1 pathway. However, whether CGA can resist apoptosis by regulating p21 and consequently promote activation of the Nrf2/HO-1 pathway needs further investigation. MC3T3-E1 cells were treated with dexamethasone (Dex), with or without CGA pre-treatment. Cell proliferation and cytotoxicity were measured using MTT assay and LDH release assay, respectively, and apoptosis assessed by flow cytometry. CGA significantly attenuated mitochondrial apoptosis and reversed down-regulation of p21 in osteoblastic MC3T3-E1 cells exposed to Dex. Additionally, CGA decreased Keap1 expression and promoted activation of the Nrf2/HO-1 pathway, quenching intracellular reactive oxygen species (ROS), hydrogen peroxide (H2O2) and mitochondrial superoxide overproduction boosted by Dex. Importantly, depletion of p21 by siRNA blocked ac...
Source: Free Radical Biology and Medicine - Category: Biology Authors: Tags: Free Radic Biol Med Source Type: research