title: PI3K/Akt signaling pathway is involved in the neurotrophic effect of senegenin.
abstract: Neurodegenerative diseases are frequently associated with the loss of synapses and neurons. Senegenin, extracted from the Chinese herb Polygala tenuifolia Willd, was previously found to promote neurite outgrowth and neuronal survival in primary cultured rat cortical neurons. The aim of the present study was to investigate the underlying mechanisms of senegenin-induced neurotrophic effects on rat cortical neurons. Primary cortical rat neurons were treated with various pharmacological antagonists and with or without senegenin, and subjected to MTT and western blot analysis to explore the effects of senegenin on cell survival as well as the activation of signaling pathways. Neurite outgrowth and neuronal survival induced by senegenin were significantly inhibited by A2A receptor antagonist ZM241385 and specific phosphoinositide-3 kinase (PI3K) inhibitor LY294002, but not by tropomyosin receptor kinase A receptor inhibitor K252a, mitogen-activated protein kinase kinase inhibitor PD98059 or protein kinase C inhibitor GÖ6976. Furthermore, senegenin enhanced the phosphorylation of Akt, which was blocked by LY294002. The present study revealed that the PI3K/Akt signaling pathway may be involved in the neurotrophic effects of senegenin.
authors.affiliation: Department of Pharmacy, Yan'an Hospital Affiliated to Kunming Medical University, Kunming, Yunnan 650051, P.R. China.
authors.forename: Ting
authors.initials: T
authors.lastname: Pi
authors.affiliation: Department of Pharmacy, Guangzhou Chest Hospital, Guangzhou, Guangdong 510095, P.R. China.
authors.forename: Xiao-Wen
authors.initials: XW
authors.lastname: Zhou
authors.affiliation: Department of Pharmacology, School of Medicine, Jinan University, Guangzhou, Guangdong 510632, P.R. China.
authors.forename: Liang
authors.initials: L
authors.lastname: Cai
authors.affiliation: Department of Pharmacology, School of Medicine, Jinan University, Guangzhou, Guangdong 510632, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, School of Medicine, Jinan University, Guangzhou, Guangdong 510632, P.R. China.
authors.forename: Chao-Fen
authors.initials: CF
authors.lastname: Su
authors.affiliation: Department of Anatomy, Li Ka‑shing Faculty of Medicine of The University of Hong Kong, Hong Kong 999077, SAR, P.R. China.
authors.forename: Wu-Tian
authors.initials: WT
authors.lastname: Wu
authors.affiliation: Department of Pharmacy, Yan'an Hospital Affiliated to Kunming Medical University, Kunming, Yunnan 650051, P.R. China.
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Ren
authors.affiliation: Department of Pharmacology, School of Medicine, Jinan University, Guangzhou, Guangdong 510632, P.R. China.
authors.forename: Huan-Min
authors.initials: HM
authors.lastname: Luo
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002867:Chromones / Q000008:administration & dosage; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage* / Q000737:chemistry; D006801:Humans; D009025:Morpholines / Q000008:administration & dosage; D016501:Neurites / Q000187:drug effects / Q000473:pathology; D019636:Neurodegenerative Diseases / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000096:biosynthesis* / Q000235:genetics; D031801:Polygala / Q000737:chemistry; D061251:Primary Cell Culture; D051057:Proto-Oncogene Proteins c-akt / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D014227:Triazines / Q000008:administration & dosage; D014230:Triazoles / Q000008:administration & dosage
chemical_list: D002867:Chromones; D004365:Drugs, Chinese Herbal; D009025:Morpholines; D014227:Triazines; D014230:Triazoles; C097270:ZM 241385; C493220:tenuigenin; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt