Protective effect of selaginellin on glutamate-induced cytotoxicity and apoptosis in differentiated PC12 cells

Abstract

L-glutamate plays a key role in neuronal cell death associated with many neurodegenerative conditions such as cerebral ischemia, hypoxia, Alzheimer's, Huntington's, and Parkinson's diseases. Selaginellin, a component extracted from Saussurea pulvinata (Hook.et Grev.) Maximo, was assessed for its ability to protect rat pheochromocytoma (PC12) cells against oxidative toxicity induced by glutamate. The differentiated PC12 cells were pretreated with various concentrations (10(-7), 3 x 10(-7), or 10(-6) M) of selaginellin for 1 h prior to exposure to L-glutamate. Selaginellin was shown to protect PC12 cells against glutamate toxicity, as determined by characteristic morphological features, lactate dehydrogenase release and cell viability, and apoptosis as evaluated by Hoechst 33342 staining assay and caspase-3 activity. In addition, the increase in levels of reactive oxygen species and decrease in klotho gene expression induced by glutamate were significantly reversed by selaginellin. Our study suggests that selaginellin has a neuroprotective effect against L-glutamate-induced neurotoxicity through mechanisms related to anti-oxidation and anti-apoptosis via scavenging reactive oxygen species and up-regulating the expression of klotho gene.

The Neuroprotective Effect of Klotho is Mediated via Regulation of Members of the Redox System

“…Klotho was found down-regulated in PC12 cells exposed to glutamate (55) and in hippocampal samples from epilepsy patients (56). Other reports suggested the important role of Klotho in the regulation of endoplasmic reticulum stress in SH-SY5Y cells (57) and in the neuroprotective effect of a plant antioxidant, ligustilide, in an AD mouse model (45).…”

Involvenflavones A–F, six new flavonoids with 3′-aryl substituent from Selaginella involven

“…The IR spectrum revealed the presence of hydroxyl (3250 cm −1 ), conjugated carbonyl (1661, 1652 cm −1 ), aromatic (1600, 1555 and 1504 cm −1 ) groups. The UV spectrum of 1 showed absorption maxima 3 3.82 s 3.79 s 3.79 s Table 2 13 C NMR spectroscopic data for compounds 1-6 (DMSO-d 6 , 125 MHz). 3.82 (3H, s), and two meta-coupled proton signals at δ H 6.37 (1H, d, J = 2.5 Hz, H-6), 6.83 (1H, d, J = 2.5 Hz, H-8), and also exhibited the signals of the glucuronopyranosyl (GlcA) group at δ H 3.0-5.0.…”

“…1). The Fraction F was purified by semi-preparative HPLC (35% ACN-H 2 O, 3.0 ml/min, 254 nm) used to obtain compounds 5 (6.0 mg) and 6 (10.0 mg). …”

Protective effects of peel and seed extracts of Citrus aurantium on glutamate-induced cytotoxicity in PC12 cell line

“…PC12 cell line is derived from a pheochromocytoma of rat adrenal medulla. This cell model is also widely applied to study cellular glutamate toxicity [38]. Therefore, it is an appropriate model to investigate the protective effect of the compounds on glutamate toxicity.…”

“…PC12 cells are more sensitive to glutamate injury; therefore, this cell model is also widely applied to study cellular glutamate toxicity [38]. Results showed that the pretreatment with C. aurantium peel and seed extracts can decrease glutamate-toxicity with different potencies.…”