title: Madecassoside prevents Aβ(25-35)-induced inflammatory responses and autophagy in neuronal cells through the class III PI3K/Beclin-1/Bcl-2 pathway.
abstract: Inflammatory responses and autophagy have been implicated in the amyloid-β (Aβ) aggregation in Alzheimer's disease (AD) due to recycling cellular waste and eliminating toxic protein aggregates. Madecassoside (Mad), a triterpenoid saponin compound, has been found to improve impaired cognitive function. However, little was known about the protection of Mad nerve cells against inflammation response and autophagy, as well as their underlying mechanism. In the present study, we investigated whether Mad could prevent Aβ25-35-induced inflammatory responses and autophagy, as well as the possible mechanism. Transmission electron microscopy results showed that Mad could significantly reduce Aβ25-35-induced autophagosomes in neural cells. Mad could also increase cell viability whereas decrease remarkably LDH leakage in Aβ25-35-induced neural cells. Both ELISA assay and western blot showed that Mad attenuated inflammatory cytokines including tumor necrosis factor (TNF)-α, interleukin (IL)-10, IL-6 and COX-2 production. Moreover, western blot results showed that Mad could block the conversion of light chain3-I (LC3-I) to light chain3-II (LC3-II), reduce Beclin-1, whereas increase anti-apoptotic protein Bcl-2 level. The levels of Beclin-1 and hVps34 in control vector-transfected NG108-15 neural cells but not in Bcl-2 transfected NG108-15 neural cells were reduced by Mad. The levels of inflammatory cytokines including TNF-α and IL-6 productions decreased significantly by the treatment with Mad. These results demonstrated that Mad protected neural cells against inflammation and autophagy induced by Aβ25-35 through the class III PI3K/Beclin-1/Bcl-2 pathway. Our findings provide evidences for the beneficial effect of Mad on the treatment of AD.
authors.affiliation: Second Department of Neurosurgery, Xinxiang Central Hospital, Xinxiang, 453003 Henan Province, People's Republic of China.
authors.forename: Baoshun
authors.initials: B
authors.lastname: Du
authors.affiliation: Department of Pathology, Xinxiang Medical University, Xinxiang, 453003 Henan, People's Republic of China.
authors.forename: Zheying
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Xinxiang Medical University, Xinxiang, 453003 Henan, People's Republic of China. Electronic address: linaxxmu@163.com.
authors.forename: Na
authors.initials: N
authors.lastname: Li
mesh_terms: D016229:Amyloid beta-Peptides / Q000276:immunology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D051017:Apoptosis Regulatory Proteins / Q000276:immunology; D001343:Autophagy / Q000187:drug effects; D000071186:Beclin-1; D002460:Cell Line; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000276:immunology; D006801:Humans; D016753:Interleukin-10 / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000276:immunology; D009474:Neurons / Q000187:drug effects* / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology*; D019869:Phosphatidylinositol 3-Kinases / Q000276:immunology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000276:immunology; D014315:Triterpenes / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D016229:Amyloid beta-Peptides; D000893:Anti-Inflammatory Agents; D051017:Apoptosis Regulatory Proteins; D000071186:Beclin-1; D051546:Cyclooxygenase 2; D016753:Interleukin-10; D015850:Interleukin-6; D008869:Microtubule-Associated Proteins; D010446:Peptide Fragments; D019869:Phosphatidylinositol 3-Kinases; D019253:Proto-Oncogene Proteins c-bcl-2; D014315:Triterpenes; D014409:Tumor Necrosis Factor-alpha; C115010:Becn1 protein, mouse; C480860:Map1lc3b protein, mouse; C074636:amyloid beta-protein (25-35); C093443:madecassoside; C077623:Ptgs2 protein, mouse
keywords: Alzheimer's disease; Autophagy; Aβ deposition; Inflammatory responses; Madecassoside; PI3K/Beclin-1/Bcl-2 pathway