title: Protective effect of diosmin on LPS-induced apoptosis in PC12 cells and inhibition of TNF-α expression.
abstract: Several studies have demonstrated a link between increased pro-inflammatory mediators and apoptosis in neurodegenerative diseases. It has been reported that lipopolysaccharide (LPS) induces apoptosis mostly through the production of TNF-α. In this study, we investigated the possible protective and anti-inflammatory mechanisms of diosmin, a natural flavone glycoside, on LPS-induced PC12 cells death through inhibition of TNF-α production. PC12 Cells were pretreated with diosmin for 2h prior to LPS treatment for 48 h to assess PC12 cells viability, TNF-α expression, and cell death mechanisms. Diosmin significantly increased cells survival and suppressed LPS-induced TNF-α in a concentration-dependent manner. Diosmin also significantly reduced the DNA fragmentation of LPS-induced cells, and its anti-apoptotic effect was confirmed by the decrease in the expression of pro-apoptotic protein Bad and the increase in the expression of anti-apoptotic protein Bcl-2 on Western blot analysis. Furthermore, diosmin inhibited LPS-induced caspase-3 activation further confirming its anti-apoptotic effects. This is the first study to report the anti-inflammatory and anti-apoptotic effects of diosmin via inhibition of TNF-α and a caspase-dependent pathway in neuronal PC12 cells. These results support the potential for diosmin to be investigated as a potential agent for the treatment of neurodegenerative diseases.
authors.affiliation: Division of Pharmaceutical Sciences, Arnold and Marie Schwartz College of Pharmacy and Health Sciences, Long Island University, Brooklyn, NY 11201, USA.
authors.forename: Sanjay L
authors.initials: SL
authors.lastname: Dholakiya
authors.forename: Kenza E
authors.initials: KE
authors.lastname: Benzeroual
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D004145:Diosmin / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic; D008070:Lipopolysaccharides / Q000494:pharmacology; D009474:Neurons / Q000166:cytology / Q000187:drug effects; D016716:PC12 Cells; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000235:genetics; D051025:bcl-Associated Death Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; C494821:Bad protein, rat; D008070:Lipopolysaccharides; D019253:Proto-Oncogene Proteins c-bcl-2; D014409:Tumor Necrosis Factor-alpha; D051025:bcl-Associated Death Protein; D004145:Diosmin; C505410:Casp3 protein, rat; D053148:Caspase 3