The herbal compound geniposide rescues formaldehyde-induced apoptosis in N2a neuroblastoma cells  

作　　者：CHEN JinYan SUN MengRu WANG XingHua LU Jing WEI Yan TAN Yan LIU Ying GTZ Jürgen HE RongQiao HUA Qian 

机构地区：[1]Beijing University of Chinese Medicine [2]Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of Queensland,Brisbane [3]Institute of Biophysics,Chinese Academy of Sciences

出　　处：《Science China(Life Sciences)》2014年第4期412-421,1-3,共10页中国科学（生命科学英文版）

基　　金：supported by the National Basic Research Program of China(2012CB911004,2010CB912303);Queensland-Chinese Academy of Sciences Biotechnology Fund(GJHZ1131,GJHZ201302)

摘　　要：The herbal medicine Tong Luo Jiu Nao （TLJN） contains geniposide （GP） and ginsenoside Rgl at a molar ratio of i0：1. Rgl 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 amyloi- dogenic 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 in- gredient 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, mor- phology 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 signifi- cantly 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 ef- ficacy. This presents purified GP as a drug or lead compound for the treatment of AD.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.

关 键 词：Alzheimer＇s disease apoptosis FORMALDEHYDE GENIPOSIDE NEUROPROTECTION panax notoginseng saponin Tong Luo Jiu Nao 

分 类 号：R285.5[医药卫生—中药学]