Pinocembrin Protects SH-SY5Y Cells Against MPP+-Induced Neurotoxicity Through the Mitochondrial Apoptotic Pathway

Abstract

Pinocembrin (PB), the most abundant flavonoid in propolis, has been proven to have neuroprotective property against neurotoxicity in vivo and in vitro. Our recent study demonstrated the neuroprotective effect of PB against Aβ25-35-induced SH-SY5Y neurotoxicity. However, the mechanism as how PB can induce neuroprotection is not known. In the present study, we demonstrate here that PB abrogates the effects of the neurotoxin 1-methyl-4-phenylpyridinium (MPP(+)) which mimics Parkinson's disease (PD) with elevation of intracellular reactive oxygen species (ROS) level and apoptotic death. We found that pretreatment of SH-SY5Y cells with PB significantly reduced the MPP(+)-induced loss of cell viability, the generation of intracellular ROS, apoptotic rate, and the cleavage of caspase-3. PB strikingly inhibited MPP(+)-induced mitochondrial dysfunctions, including lowered membrane potential, decreased Bcl-2/Bax ratio, and the release of cytochrome c. Overall, these results suggest that PB is intimately involved in inhibiting MPP(+)-induced loss of mitochondrial function and induction of apoptosis that contributes toward neuronal survival. These data indicated that PB might provide a valuable therapeutic strategy for the treatment of PD.

Natural Products and Their Bioactive Compounds: Neuroprotective Potentials against Neurodegenerative Diseases

“…Taken together, all these findings suggest that propolis displays neuroprotective through multiple pathways which might be attributed by the presence of bioactive compounds in propolis as well as their combination of multitarget compound acting on the different pathways. Several studies have reported on the neuroprotective effect of compounds present in the propolis in various study models of neurodegenerative diseases; for example, kaempferol [80,83], chrysin [84], pinocembrin [85][86][87][88][89][90][91][92][93][94][95][96], and caffeic acid phenethyl ester [97][98][99][100][101][102][103][104][105][106][107][108]. ese studies reported and suggested that these bioactive compounds may protect against neurodegenerative characteristics of neurodegenerative diseases Evidence-Based Complementary and Alternative Medicine and the multiple mechanisms of the neuroprotective effect of compounds tested could be potentially involved.…”

Can Co-Activation of Nrf2 and Neurotrophic Signaling Pathway Slow Alzheimer’s Disease?

“…Pinocembrin , an herb flavonoid, that showed neuroprotective effects in cerebral ischemic injury [191], glutamate toxicity [192], APPsw-overexpressing SH-SY5Y cells [193], and vascular dementia animal [194,195] appears to use the Nrf2-ARE system for its neuroprotective action [196]. Pinocembrain increased nuclear Nrf2 and activated the ARE-mediated expression of HO-1 and λ-GCS in SH-SY5Y cells, thus protecting the cells from 6-hydroxydopamine (6-OHDA)-induced oxidative stress [196].…”

The Natural Flavonoid Pinocembrin: Molecular Targets and Potential Therapeutic Applications

“…These data provide strong evidence that pinocembrin might protect the brain by targeting neuroinflammation. Finally, pinocembrin was reported to decrease neurotoxicity and inhibit mitochondrial dysfunction in 1-methyl-4-phenylpyridinium (MPP(+))–treated SH-Sy5y cells [52] and to attenuate neuronal death through the Nrf2/ARE pathway in 6-OHDA-treated SH-Sy5y cells [53], suggesting a potential application in Parkinson’s disease.…”