Mild Mitochondrial Depolarization is Involved in a Neuroprotective Mechanism of Citrus sunki Peel Extract

Abstract

Mitochondrial membrane potential (∆Ψm ) contributes to determining a driving force for calcium to enter the mitochondria. It has been demonstrated that even a small mitochondrial depolarization is sufficient to prevent mitochondrial calcium overload and the subsequent apoptosis. Therefore, mild mitochondrial depolarization has been recently evaluated as a novel mechanism of neuroprotection via inhibiting neurotoxic mitochondrial calcium overload during neuronal insults. In the present study, using both real-time recording and flow cytometric analyses of ∆Ψm , we demonstrated that ethanolic peel extract of Citrus sunki Hort. ex Tanaka (CPE) and its active compounds are capable of inducing a mild mitochondrial depolarization. Polymethoxylated flavones such as nobiletin and tangeretin were found as the active compounds responsible for CPE effects on ∆Ψm . Neuronal viability was significantly increased in a dose-dependent manner by CPE treatment in H2 O2 -stimulated HT-22 cells as an in vitro neuronal insult model. CPE treatment significantly inhibited H2 O2 -induced apoptotic processes such as chromatin condensation, caspase 3 activation and anti-poly (ADP-ribose) polymerase (PARP) cleavage. CPE treatment significantly blocked mitochondrial calcium overload in H2 O2 -stimulated HT-22 neurons as indicated by rhod-2 acetoxymethyl ester. Taken together, our findings suggest that CPE and its active compounds may be considered as promising neuroprotective agents via inducing a mild mitochondrial depolarization.

African locust bean (Parkia biglobosa, Jacq Benth) leaf extract affects mitochondrial redox chemistry and inhibits angiotensin-converting enzyme in vitro

“…This might account for the superior mitochondrial ROS mitigating property of PBE over catechin. Such mild depolarization has been attributed to the neuroprotective effect of a plant extract [42] and the protection of cardiomyocytes from oxidative stress [40]. In the case of PBE, further studies are warranted to identify the active molecules and the underlying mechanisms involved in its mild mitochondrial potential depolarization propensity.…”

Parkia biglobosaImproves Mitochondrial Functioning and Protects against Neurotoxic Agents in Rat Brain Hippocampal Slices

“…The neuroprotective effect of a plant extract was once attributed to the mild depolarization of ΔΨ m [59]. The mitochondrial membrane potential (ΔΨ m ) contributes significantly to the extent of ROS production and with increased production occurring at high potentials [60].…”

Inhibitory Effects of Nobiletin on Hepatocellular Carcinoma In Vitro and In Vivo

“…For instance, it has been shown that soybean isoflavones inhibit growth of prostate cancer cell in vivo (Choi et al ., ) and in vitro (Bosland et al ., ; Hikosaka et al ., ). The intake of citrus fruits was considered beneficial for health (Onda et al ., 2013; Wu et al ., ), and in a recent literature review of citrus flavonoids, a broad spectrum of biological activities, including anticarcinogenic and antitumor activities, was discussed (Gullett et al ., ; Lu et al ., 2012). It is commonly accepted that cancer development can be prevented by the ingestion of certain foods (Stavric, ), and flavonoids in citrus fruits and juices are examples of the most prominent cancer‐preventing agents.…”