title: 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 downregulated inflammatory gene and protein expression, including interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, HMGB1, high mobility group box 1 protein (HMGB1), cyclooxygenase-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.
authors.affiliation: Department of Neurosurgery, Traffic Hospital of Shandong Province, Jinan, Shandong 250031, P.R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China.
authors.forename: You Song
authors.initials: YS
authors.lastname: Xu
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China.
authors.forename: Miao Lin
authors.initials: ML
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China.
authors.forename: Chao
authors.initials: C
authors.lastname: Cheng
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China.
authors.forename: Rui
authors.initials: R
authors.lastname: Bian
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China.
authors.forename: Hao
authors.initials: H
authors.lastname: Yuan
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China.
authors.forename: Ting
authors.initials: T
authors.lastname: Guo
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China.
authors.forename: Lin Lin
authors.initials: LL
authors.lastname: Zhu
authors.affiliation: Department of Neurosurgery, The 2nd Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116027, P.R. China.
authors.forename: Hang
authors.initials: H
authors.lastname: Zhou
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D044950:Flavanones / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000633:toxicity*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D016716:PC12 Cells; D051381:Rats
chemical_list: D044950:Flavanones; D008070:Lipopolysaccharides; D009419:Nerve Tissue Proteins; C005274:naringin