title: The herbal compound geniposide rescues formaldehyde-induced apoptosis in N2a neuroblastoma cells.
abstract: The herbal medicine Tong Luo Jiu Nao (TLJN) contains geniposide (GP) and ginsenoside Rg1 at a molar ratio of 10:1. Rg1 is the major component of another herbal medicine, panax notoginseng saponin (PNS). TLJN has been shown to strengthen brain function in humans, and in animals it improves learning and memory. We have previously shown that TLJN reduces amyloidogenic processing in Alzheimer's disease (AD) mouse models. Together this suggests TLJN may be a potential treatment for patients with dementia. Because chronic damage of the central nervous system by formaldehyde (FA) has been presented as a risk factor for age-associated cognitive dysfunction, in the present study we investigated the protective effect of both TLJN and GP in neuron-like cells exposed to FA. FA-exposed murine N2a neuroblastoma cells were incubated with TLJN, its main ingredient GP, as well as PNS, to measure cell viability and morphology, the rate of apoptosis and expression of genes encoding Akt, FOXO3, Bcl2 and p53. The CCK-8 assay, cytoskeletal staining and flow cytometry were used to test cell viability, morphology and apoptosis, respectively. Fluorescent quantitative real-time PCR (qRT-PCR) was used to monitor changes in gene expression, and HPLC to determine the rate of FA clearance. Treatment of N2a cells with 0.09 mmol L(-1) FA for 24 h significantly reduced cell viability, changed cell morphology and promoted apoptosis. Both TLJN and GP conferred neuroprotection to FA-treated N2a cells, whereas PNS, which had to be used at lower concentrations because of its toxicity, did not. Our data demonstrate that TLJN can rescue neuronal damage caused by FA and that its main ingredient, GP, has a major role in this efficacy. This presents purified GP as a drug or lead compound for the treatment of AD.
authors.forename: JinYan
authors.initials: J
authors.lastname: Chen
authors.forename: MengRu
authors.initials: M
authors.lastname: Sun
authors.forename: XingHua
authors.initials: X
authors.lastname: Wang
authors.forename: Jing
authors.initials: J
authors.lastname: Lu
authors.forename: Yan
authors.initials: Y
authors.lastname: Wei
authors.forename: Yan
authors.initials: Y
authors.lastname: Tan
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.forename: Jürgen
authors.initials: J
authors.lastname: Götz
authors.forename: RongQiao
authors.initials: R
authors.lastname: He
authors.forename: Qian
authors.initials: Q
authors.lastname: Hua
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival; D002490:Central Nervous System / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D003072:Cognition Disorders / Q000503:physiopathology; D003599:Cytoskeleton / Q000378:metabolism; D003704:Dementia / Q000628:therapy; D005557:Formaldehyde / Q000737:chemistry*; D039823:Iridoids / Q000737:chemistry*; D007858:Learning / Q000502:physiology; D008516:Medicine, Chinese Traditional; D008568:Memory / Q000502:physiology; D051379:Mice; D009447:Neuroblastoma / Q000378:metabolism*; D028321:Plant Preparations / Q000737:chemistry; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D039823:Iridoids; D028321:Plant Preparations; C007835:geniposide; D005557:Formaldehyde