Cytoprotective Effects of Punicalagin on Hydrogen–Peroxide–Mediated Oxidative Stress and Mitochondrial Dysfunction in Retinal Pigment Epithelium Cells

Abstract

The retinal pigment epithelium (RPE) is a densely pigmented, monostratified epithelium that provides metabolic and functional support to the outer segments of photoreceptors. Endogenous or exogenous oxidative stimuli determine a switch from physiological to pathological conditions, characterized by an increase of intracellular levels of reactive oxygen species (ROS). Accumulating evidence has elucidated that punicalagin (PUN), the major ellagitannin in pomegranate, is a potent antioxidant in several cell types. The present study aimed to investigate the protective effect of PUN on mitochondrial dysfunction associated with hydrogen peroxide (H2O2)–induced oxidative stress. For this purpose, we used a human RPE cell line (ARPE–19) exposed to H2O2 for 24 h. The effects of PUN pre–treatment (24 h) were examined on cell viability, mitochondrial ROS levels, mitochondrial membrane potential, and respiratory chain complexes, then finally on caspase–3 enzymatic activity. The results showed that supplementation with PUN: (a) significantly increased cell viability; (b) kept the mitochondrial membrane potential (ΔΨm) at healthy levels and limited ROS production; (c) preserved the activity of respiratory complexes; (d) reduced caspase–3 activity. In conclusion, due to its activity in helping mitochondrial functions, reducing oxidative stress, and subsequent induction of cellular apoptosis, PUN might be considered a useful nutraceutical agent in the treatment of oxidation–associated disorders of RPE.

Punicalagin Attenuates Neuronal Apoptosis by Upregulating 5-Hydroxymethylcytosine in the Diabetic Mouse Brain

“…In recent years, studies on the improvement of mitochondrial functions by PU has been reported gradually. ,, Our study confirmed that PU effectively improved the mitochondrial function in the diabetic mouse brain. Meanwhile, we also found that PU maintained the Krebs cycle homeostasis.…”

Cytoprotective Effect of Idebenone through Modulation of the Intrinsic Mitochondrial Pathway of Apoptosis in Human Retinal Pigment Epithelial Cells Exposed to Oxidative Stress Induced by Hydrogen Peroxide

“…Analysis of the activity of mitochondrial respiratory complexes (I-III) was performed on purified mitochondria [ 26 ]. Mitochondria were isolated using a mitochondria/cytosol fractionation kit (MBL, Medical & Biological Laboratories, 200 Dexter Ave., Watertown, MA 02472, USA).…”

“…With this in mind, the present study aims to obtain a more comprehensive understanding of the mechanisms regulating the IDB cytoprotective effect in the RPE at both the cytoplasmic and mitochondrial levels. We used an in vitro experimental model, previously developed by our laboratory, in which RPE cells (human ARPE-19 cell line) were exposed to H 2 O 2 for 24 h [ 26 ]. The correlation between the RPE cells pre-treated with IDB (24 h) and cell viability, direct stimulation of Nrf2, as well as the modulation of the Bcl-2 family proteins (Bax and Bcl-2), were examined in our experimental paradigm.…”

Shipi Shugan Decoction Protected against Sequela of Pelvic Inflammatory Disease via Inhibiting SIRT1/NLRP3 Signaling Pathway in Pelvic Inflammatory Disease Rats

“…Mitochondrial dysfunction and oxidative stress injury were important pathophysiological mechanisms of PID [ 22 , 23 ]. It was reported that the reduced activity of mitochondrial respiratory chain complex 1 could promote ROS accumulation, leading to depolarization of mitochondrial membrane potential and changes in membrane permeability [ 24 , 25 ]. Superoxide radicals, hydrogen peroxide, hydroxyl radicals, and so on are collectively referred to as ROS [ 26 , 27 ].…”