Protective effects of fustin, a flavonoid from Rhus verniciflua Stokes, on 6-hydroxydopamine-induced neuronal cell death

Abstract

Abstract6-Hydroxydopamine (6-OHDA) is a neurotoxin and is commonly used to generate experimental models of Parkinson's disease (PD). In this study, we investigated the signaling molecules involved in the 6-OHDA-induced cell death using a neuronal catecholaminergic cell line (SK-N-SH cells), and the protective effect of fustin, a flavonoid from Rhus verniciflua Stokes, on 6-OHDA-induced neuronal death. 6-OHDA significantly increased levels of reactive oxygen species (ROS), intracellular Ca 2+ ([Ca 2+ ] i ), and p38 phosphorylation. In addition, this ROS increase by 6-OHDA was reduced by pretreatment with N-acetylcysteine (NAC), a free radical scavenger, but not by bis-(o-aminophenoxy)-ethane-N,N,N,Ntetraacetic acid (BAPTA), a Ca 2+ chelator. However, the [Ca 2+ ] i increase induced by 6-OHDA was suppressed by NAC. Moreover, pretreatment with NAC or BAPTA significantly prevented the 6-OHDAinduced increases in p38 phosphorylation, Bax/ Bcl-2 ratio, and caspase-3 activity. Although 6-OHDA-increased phosphorylation of p38 was prevented by NAC or BAPTA, inhibition of p38 by SB203580 did not suppress ROS, Bax/Bcl-2 ratio, or caspase-3 activity increases, and only partially prevented 6-OHDA-induced cell death, thus demonstrating that p38 activation is a component of a signaling pathway leading to the initiation of 6-OHDA-induced cell death, which acts in parallel with an ROS-Ca 2+ -Bcl-2-caspase-3 pathway. Moreover, fustin not only suppressed 6-OHDA-induced cell death in a concentration-dependent manner but also blocked 6-OHDA-induced increases in ROS, [Ca 2+ ] i , Bax/Bcl-2 ratio, caspase-3 activity, and p38 phosphorylation. These results suggest that fustin exerts neuroprotection against 6-OHDA-induced cell death.

Neuroprotective effects of dimerumic acid and deferricoprogen fromMonascus purpureusNTU 568-fermented rice against 6-hydroxydopamine-induced oxidative stress and apoptosis in differentiated pheochromocytoma PC-12 cells

“…Cytosolic cytochrome c binds to apoptosome, resulting in caspase-9 activation and following activation of caspase-3 (Kwon et al 2003). There are several studies showing that 6-OHDA induces activation of caspase-3 (Han et al 2003;Chen et al 2004;Hanrott et al 2006) and that 6-OHDA toxicity is related to the altered expression of Bcl-2 family proteins (Tsao et al 2002(Tsao et al -2003Park et al 2007). In the present study, we found that 6-OHDA induced DNA fragmentation, activated caspase-3, down-regulated Bcl-2, and up-regulated Bax.…”

Preparative Isolation and Purification of Neuroprotective Compounds from <i>Rhus verniciflua</i> by High Speed Counter-Current Chromatography

“…17) The extract of R. verniciflua itself, as well as isolated compound, fustin have also found to attenuate neurotoxicity caused by negative insults such as rotenone and 6-hydroxydopamine. 18,19) These results suggest that R. verniciflua can act as a neuroprotectant in certain situations.…”

“…All analyses were performed using an Waters Atlantis C 18 Statistical Analysis The data are expressed as a mean percentage of the control value plus standard error of the mean (S.E.M.). Statistical comparisons were made using a one-way analysis of variance (ANOVA) followed by a Dunnett's test.…”

Protective effects of ethyl acetate extract of Eclipta prostrata against 6-hydroxydopamine-induced neurotoxicity in SH-SY5Y cells

“…The augmentation of apoptotic downstream signalling was enhanced in response to 6-OHDA-derived cellular oxidative stress. Several studies reported that 6-OHDA could trigger the elevation of Bax/Bcl-2 ratio 28,29 . The ratio between pro-apoptotic protein Bax and antiapoptotic protein Bcl-2 is thought to play a role in apoptosis.…”