Protective effect of naringin against the LPS-induced apoptosis of PC12 cells: Implications for the treatment of neurodegenerative disorders

Abstract

Several studies have demonstrated that increased apoptosis plays an essential role in neurodegenerative disorders. It has been demonstrated that lipopolysaccharide (LPS) induces apoptosis largely through the production of intracellular reactive oxygen species (ROS) and inflammatory mediators. In this study, we investigated the potential protective mechanisms of naringin (Nar), a pummelo peel extract, on LPS-induced PC12 cell apoptosis. Nar pre-conditioning prior to stimulation with LPS for 18 h was a prerequisite for evaluating PC12 cell viability and the protective mechanisms of Nar. Nar significantly improved cell survival in a time- and concentration-dependent manner. On the one hand, Nar downregulated cytochrome P450 2E1 (CYP2E1), inhibited the release of ROS, mitigated the stimulation of oxidative stress, and rectified the antioxidant protein contents of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), superoxide dismutase (SOD)2 and glutathione synthetase (GSS). On the other hand, Nar down-regulated inflammatory gene and protein expression, including interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, HMGB1, high mobility group box 1 protein (HMGB1), cyclo-oxygenase-2 (COX-2), the Toll-like receptor 4 (TLR4)-myeloid differentiation factor 88 (MyD88)-TNF receptor-associated factor 6 (TRAF6) path way and downstream mitogen activated protein kinase (MAPK) phosphorylation, activator protein transcription factor-1 (AP-1) and nuclear factor (NF)-κB. Moroever, Nar markedly attenuated the cytochrome c shift from the mitochondria to the cytosol and regulated caspase-3-related protein expression. To the best of our knowledge, this is the first study to report the antioxidant, anti-inflammatory and anti-apoptotic effects of Nar in neuronal-like PC12 cells. These results suggest that Nar can be utilized as a potential drug for the treatment of neurodegenerative disorders.

CZ2HF mitigates β-amyloid 25-35 fragment-induced learning and memory impairment through inhibition of neuroinflammation and apoptosis in rats

“…Agents. donepezil hydrochloride (1511010) was obtained from Affiliated Hospital of Zunyi Medical University (Zunyi, China), Aβ [25][26][27][28][29][30][31][32][33][34][35] (the amino acid sequence is Gly-Ser-Asn-Lys-Gly-A la-Ile-Ile-Gly-Leu-Met) was purchased from Sigma-Aldrich (cat. no.…”

“…All experiments were approved by the Ethics committee and performed according to the current guide for the care and use of laboratory animal standard, which was set up by Zunyi Medical University Animal Studies committee (argument number [2015] 2-043). The rats were randomly divided into 7 groups as follows: i) Sham; ii) sham+cZ2HF (400 mg/kg); iii) model (Aβ [25][26][27][28][29][30][31][32][33][34][35] ); iv) Aβ [25][26][27][28][29][30][31][32][33][34][35] +cZ2HF (100 mg/kg); v) Aβ [25][26][27][28][29][30][31][32][33][34][35] +cZ2HF (200 mg/kg); vi) Aβ [25][26][27][28][29][30][31][32][33][34][35] +cZ2HF (400 mg/kg); and vii) Aβ 25-35 +donepezil (1.0 mg/kg) as the positive drug group (n=14 rats per group. Briefly, Aβ [25][26][27]…”

“…Subsequently, Sd rats were anesthetized with an intraperitoneal injection of 2% pentobarbital sodium, the rat's brain was fixed a stereotaxic device, and the following hippocampus needle coordinates were used: 3.5 mm posterior to the bregma, 2.5 mm lateral to the sagittal suture, 3.5 mm beneath the surface of brain. The needle was retained in the bilateral hippocampi for 5 min and the 5 µl Aβ [25][26][27][28][29][30][31][32][33][34][35] was injected. Various doses of cZ2HF were administered orally daily for a continuous period for 15 days.…”

“…The Morris water maze test (MWM) was performed in order to determine the learning and memory function of the rats from the 7 groups as described in our previous study (19). The rats were trained and exposed to 4 successive memory acquisition trials in the MWM to analyze their capacity to escape and find the platform, which was performed daily between days 11 and 16 after the Aβ [25][26][27][28][29][30][31][32][33][34][35] injection. On day 16, the spatial probe experiment was performed to detect the ability of spatial memory.…”

“…However, whether cZ2HF is capable of alleviating learning and memory impairment in Alzheimer's disease (Ad) remains to be elucidated. The present study was designed to explore the effect and mechanism of cZ2HF on β-amyloid [25][26][27][28][29][30][31][32][33][34][35] )-induced impairment in the learning and memory of rats. Morris water maze test was used to determine spatial learning and memory ability in Aβ 25-35 -induced Ad rats and hippocampal neuronal damage and apoptosis were observed using hematoxylin and eosin staining, Nissl staining and terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling (TUNEL) assays, respectively.…”