Activation of the Nrf2/HO-1 signaling pathway contributes to the protective effects of coptisine against oxidative stress-induced DNA damage and apoptosis in HaCaT keratinocytes

Abstract

In this study, the protective effect of coptisine on the oxidative damage-mediated apoptosis was evaluated in cultured human HaCaT keratinocytes. The results demonstrate that preincubation of cells with coptisine prior to H 2 O 2 stimulation resulted in significant inhibition of cytotoxicity and DNA damage associated with the inhibition of reactive oxygen species (ROS) accumulation. Coptisine also restored H 2 O 2-induced mitochondrial dysfunction and decrease of ATP production, and prevented apoptosis by inhibiting Bax/Bcl-2 ratio, caspase-3 activity, and poly(ADP-ribose) polymerase degradation. Interestingly, the expressions of nuclear factor-erythroid-2-related factor 2 (Nrf2) and its active form, phosphorylated Nrf2, were strikingly promoted by coptisine in the presence of H 2 O 2 , which was associated with a marked increase in the expression of heme oxygenase-1 (HO-1). However, coptisine-induced HO-1 expression was completely abrogated by Nrf2-specific small interfering RNA (Nrf2-siRNA), which suggests that the increased expression of HO-1 by coptisine is Nrf2-dependent. In addition, Nrf2-siRNA transfection significantly eliminated the protective effect of coptisine on H 2 O 2-induced cytotoxicity, and this effect was similar to that by zinc protoporphyrin IX (ZnPP), an HO-1 specific inhibitor. Furthermore, the protective effects of coptisine against H 2 O 2-induced cytotoxicity were abolished by ZnPP, indicating that coptisine protects keratinocytes against oxidative stress-induced injury through activation of the Nrf2/HO-1 signaling pathway.

Tetrahydropyrimidines, ZL-5015 Alleviated Lipopolysaccharide (LPS)-Induced Acute Pneumonia in Rats by Activating the NRF-2/HO-1 Pathway

“…However, higher levels of ROS gradually decreased as doses of ZL-5015 increased. On the other hand, some studies revealed that lower levels of NRF-2 and HO-1 were associated with inflammation, oxidative stress, and production of ROS, and activation of the NRF-2/HO-1 pathway relieved inflammatory injury and oxidative damage [ 26 – 28 ]. Therefore, we detected expression of NRF-2 and HO-1 in lung tissues of the rats.…”

Inhibition of Oxidative Stress and ALOX12 and NF-κB Pathways Contribute to the Protective Effect of Baicalein on Carbon Tetrachloride-Induced Acute Liver Injury

“…In previous studies, baicalein supplementation was shown to markedly inhibit colistin-induced activation of caspases-9 and -3 in the kidney tissues of mice or inhibit CCl 4 exposure-induced mitochondrial apoptotic cell death in liver tissues of mice [ 28 , 53 ]. Similarly, Jeong and colleagues reported that baicalein treatment (100 μM) markedly inhibited H 2 O 2 -induced oxidative stress, caspases activation, and apoptosis in HEI193 Schwann cells [ 54 ]. Taken together, our results indicated that baicalein supplementation ameliorates toxin-induced oxidative stress in the liver, thereby preventing mitochondrial dysfunction and apoptotic cell death.…”

Anti-Apoptotic Role of Sanhuang Xiexin Decoction and Anisodamine in Endotoxemia

“…Among them, rhein exhibited significant anti-apoptosis in endotoxemia and showed significant protective effects against endotoxin-induced kidney injury (Yu et al, 2015). Coptisine, a major compound from Rhizoma Coptidis that clears heat and dampness, purging fire for removing the toxin has been reported to exhibit protective effects on HaCaT keratinocytes by blocking the mitochondriadependent apoptotic pathway (Choi, 2019). Furthermore, baicalin is the most reported anti-apoptotic component of Sanhuang Xiexin Decoction, showing anti-apoptotic effects in a variety of cell types, including cardiomyocytes (Liou et al, 2011;Liou et al, 2012), C2C12 myoblast (Pan et al, 2019), arterial endothelial cells (Shou et al, 2017), neuronal cells (Zheng, et al, 2015), hepatic stellate cells (Wu et al, 2018a;Wu et al, 2018b), endplate chondrocytes (Pan et al, 2017), renal cells (Zhu et al, 2016) and colonic epithelial cells (Yao et al, 2016).…”