Neuroprotective effects of orientin on hydrogen peroxide-induced apoptosis in SH-SY5Y cells

Abstract

Neurodegenerative diseases remain a global issue which affects the ageing population. Efforts towards determining their aetiologies to understand their pathogenic mechanisms are underway in order to identify a pathway through which therapeutic measures can be applied. One such pathogenic mechanism, oxidative stress (OS), is widely considered to be involved in neurodegenerative disease. Antioxidants, most notably flavonoids, have promising potential for therapeutic use as shown in in vitro and in vivo studies. In view of the importance of flavonoids for combating OS, this study investigated the neuroprotective effects of orientin, which has been reported to be capable of crossing the blood‑brain barrier. The maximum non‑toxic dose (MNTD) of orientin against SH‑SY5Y neuroblastoma cells was determined using a 3‑(4,5‑dimethylthiazol‑2‑yl)‑2,5‑diphenyltetrazolium bromide (MTT) assay. The effects of the MNTD and the half MNTD (½MNTD) of orientin on cell cycle progression and intracellular reactive oxygen species (ROS) levels, as well as the activity of caspases 3/7, 8 and 9 after exposure to 150 µM of hydrogen peroxide (H2O2) were also determined using flow cytometry, a 2',7'‑dichlorodihydrofluorescein‑diacetate (DCFH‑DA) assay and caspase assay kits, respectively. The results revealed that orientin at ≤20 µM was not cytotoxic to SH‑SY5Y cells. After treatment with orientin at the MNTD, the percentage of apoptotic cells was significantly reduced compared with that in cells treated with 150 µM H2O2 alone. The results also showed that, although orientin at the MNTD and ½MNTD did not reduce intracellular ROS levels, it significantly inhibited the activity of caspases 3/7. Caspase 9 was significantly inactivated with orientin at the MNTD. Findings from this study suggest that the neuroprotection conferred by orientin was the result of the intracellular mediation of caspase activity.

Effect of the SOD mimetic MnL4 on in vitro and in vivo oxaliplatin toxicity: Possible aid in chemotherapy induced neuropathy

“…In astrocytes, the concomitant incubation with MnL4 reduces it, whereas in SH-SY5Y, MnL4 is ineffective. An anti-apoptotic effect of antioxidants has been described in SH-SY5Y treated with noxious stimuli like MPP þ [36], 1,2-diacetylbenzene [37] or hydrogen peroxide [38]. In those reports, an exogenous oxidant stimulus has been employed; on the contrary, as already described [20], oxaliplatin is not a direct oxidant molecule.…”

Anti-amnesic effect of Dendropanax morbifera via JNK signaling pathway on cognitive dysfunction in high-fat diet-induced diabetic mice

“…Moreover, Yu et al [45] showed that orientin impeded the Aβ 1-42 -induced cellular apoptosis, and improved cognitive impairments and mitochondrial deficiency in AD rats. In addition, orientin had other physiological effects, such as antioxidant, antiglycation [46], and protective effect from mitochondrial oxidative stress-induced apoptosis [47]. Isoorientin, as an isoform of orientin, alleviates LPS-induced pro-inflammatory mediators by inhibiting the activation of mitogen-activated protein kinases (MAPKs) and nuclear factor κB (NF-κB) [48].…”

Protective effect of the orientin on noise-induced cognitive impairments in mice

“…Several recent studies have demonstrated that orientin exerts a variety of pharmacological effects, including antioxidant, anti-inflammatory, and neuroprotective effects [24,25]. For example, orientin (20 mg/kg and 40 mg/kg, intragastric administration) has shown significant antioxidant properties in improving the neuronal ultrastructure in the hippocampus of D-galactose-aged mice [26].…”