Detoxified Extract of Rhus verniciflua Stokes Inhibits Rotenone-Induced Apoptosis in Human Dopaminergic Cells, SH-SY5Y

Abstract

Rhus verniciflua Stokes (RVS), traditionally used as a food supplement and in traditional herbal medicine for centuries in Korea, is known to possess various pharmacological properties. Environmental neurotoxins such as rotenone, a specific inhibitor of complex I provide models of Parkinson's disease (PD) both in vivo and in vitro. In this study, we investigated the neuroprotective effect of RVS against rotenone-induced toxicity in human dopaminergic cells, SH-SY5Y. Cells exposed to rotenone for 24 h-induced cellular injury and apoptotic cell death. Pretreatment of cells with RVS provided significant protection to SH-SY5Y cells. Further, RVS offered remarkable protection against rotenone-induced oxidative stress and markedly inhibited mitochondrial membrane potential (MMP) disruption. RVS also attenuated the up-regulation of Bax, Caspase-9 and Caspase-3 and down-regulation of Bcl-2. Moreover, pretreatment with RVS prevented the decrease in tyrosine hydroxylase (TH) levels in SH-SY5Y cells. Interestingly, RVS conferred profound protection to human dopaminergic cells by preventing the downregulation of brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF). These results suggest that RVS may protect dopaminergic neurons against rotenone-induced apoptosis by multiple functions and contribute to neuroprotection in neurodegenerative diseases, such as PD.

Neuroprotective Effects of Bikaverin on H2O2-Induced Oxidative Stress Mediated Neuronal Damage in SH-SY5Y Cell Line

“…Choi et al (2010) reported an increased expression of TH and BDNF genes on pretreatment with T. regelii extract accounting for its neuroprotective actions. Sapkota et al (2011) reported detoxified extract of R. verniciflua prevented the downregulation of BDNF and TH against rotenone-induced toxicity. Ghaffari et al (2014) observed H. suaveolens methanol extract treatment demonstrated enhanced expression of neuronal biomarker genes BDNF and TH.…”

“…However, we observed the restoration of MMP by bikaverin pretreatment, which was dissipated with H 2 O 2 treatment. In their study, Sapkota et al (2011) showed the extract of R. verniciflua markedly inhibited MMP disruption, offering protection against rotenone-induced oxidative stress. Kwon et al (2012) reported E. ulmoides extract increased cell viability, inhibited cytotoxicity, and DNA condensation.…”

“…Many plant species in diverse regions of the world have been screened for their neuroprotective activity. Extracts of plants such as Green tea (Cho et al 2008), Tripterygium regelii (Choi et al 2010), Rhus verniciflua (Sapkota et al 2011), Eucommia ulmoides (Kwon et al 2012), Hyptis suaveolens (Ghaffari et al 2014), Bacopa monnieri (Thomas et al 2013), and Cyperus rotundus ) were reported to possess antioxidant properties and neuroprotective effects. However, there are very few reports on the neuroprotective compounds of fungal origin.…”

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.…”

GDNF and PD: Less Common Points of View

“…Moreover, GDNF immunoreactivity is markedly enhanced in the substantia nigra of rats treated with Rhus verniciflua extract. Interestingly, the neuroprotective effects of Rhus verniciflua against rotenone-induced toxicity in SH-SY5Y cells include the prevention of GDNF and BDNF down-regulation in rotenone-treated cells (Sapkota et al, 2011). Ibogaine is a psychoactive compound extracted from Tabernanthe iboga, and used for decades in African folklore medicine and rituals.…”