Cytoprotective Effects of Delphinidin for Human Chondrocytes against Oxidative Stress through Activation of Autophagy

Abstract

Antioxidant enzymes are decreased in osteoarthritis (OA) patients, implying the role of oxidative stress in osteoarthritis pathogenesis. The aim of this study was to evaluate the cytoprotective effects of delphinidin, a potent antioxidant, in human chondrocytes and the underlying mechanisms. The cytoprotective mechanism induced by delphinidin against oxidative stress (H2O2) in human chondrocytes was investigated. Cell viability and death were evaluated using proapoptotic and antiapoptotic markers such as cleaved caspase-3 (c-caspase-3), cleaved poly(ADP-ribose) polymerase N-acetylcysteine (c-PARP), Bcl-XL, and transcription factors associated with redox and inflammation regulation, including nuclear factor kappa B (NF-κB) and nuclear factor (erythroid-derived 2)-like 2 (Nrf2). Induction of autophagy was assessed by formation of LC3-II and autophagosome-(LC3 punctate, monodansylcadaverine (MDC) and acridine orange staining) in the presence or absence of an autophagy inhibitor. Treatment with delphinidin itself at concentration below 50 µM for 24 h did not affect viability of chondrocytes. Delphinidin inhibited reactive oxygen species (ROS)-induced apoptosis by significantly decreasing apoptosis markers such as c-caspase-3 and c-PARP while increasing antiapoptotic marker Bcl-XL and antioxidant response NF-κB and Nrf2 pathways. Delphinidin also activated cytoprotective autophagy to protect chondrocytes during oxidative stresses. Activation of autophagy with autophagy inducer rapamycin also inhibited ROS-induced cell death and decreased proapoptotic proteins but increased antiapoptotic protein Bcl-XL, NF-κB, and Nrf2. Delphinidin can protect chondrocytes against H2O2-induced apoptosis via activation of Nrf2 and NF-κB and protective autophagy. Thus, it can inhibit OA with protection of chondrocytes. Delphinidin can protect chondrocytes against H2O2-induced ROS with maintenance of homeostasis and redox. These results suggest that delphinidin could be used to protect chondrocytes against age-related oxidative stress and other oxidative stresses in the treatment of OA. Thus, delphinidin may play a critical role in preventing the development and progression of OA.

Phytochemical Profile, Antiradical Capacity and α-Glucosidase Inhibitory Potential of Wild Arbutus unedo L. Fruits from Central Italy: A Chemometric Approach

“…Due to their antioxidant potential, delphinidin glucosides showed the strongest scavenging activity against superoxide anion and peroxynitrite among several anthocyanins [ 32 ]. Moreover, delphinidin was reported to exert cytoprotective effects for human chondrocytes against oxidative stress [ 33 ], as well as inhibitory effects on oxidative stress in HepG2 cells [ 34 ]. To the best of our knowledge, this is the first study reporting malvidin-3-O-glucoside in A. unedo wild fruit extracts.…”

Effect of Astaxanthin on Activation of Autophagy and Inhibition of Apoptosis in Helicobacter pylori-Infected Gastric Epithelial Cell Line AGS

“…Antioxidants such as α-tocopherol and delphinidin induced autophagy by antioxidant activities [ 83 , 87 ]. α-tocopherol stimulated autophagy and reduced desmin aggregation, determined by increased levels of LC3B-II, in muscle cells [ 83 ].…”

“…Delphinidin inhibited ROS-induced apoptosis and induced autophagy. Autophagy was assessed by the formation of LC3B-II and autophagosomes (LC3B puncta and AO staining) in human chondrocytes [ 87 ]. Therefore, antioxidant compounds may increase the number of AO-positive cells and LC3B puncta.…”

Inhibitory Effect of Delphinidin on Oxidative Stress Induced by H2O2 in HepG2 Cells

“…Moreover, delphinidin could inhibit the proliferation of SKOV3 cells (ovarian cancer cells) [ 26 ] and it could prevent prostate cancer via inhibiting the apoptosis mediated by p53 [ 27 ]. Lee et al reported that delphinidin could protect chondrocytes against H 2 O 2 -mediated oxidative stress by activating NF- κ B and Nrf2 [ 28 ]. However, there is a lack of data on how delphinidin regulates Nrf2 to exert the function of antioxidant stress.…”