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. FA is a colorless, irritating gas with a high oxidation capa-

Uric formaldehyde levels are negatively correlated with cognitive abilities in healthy older adults

“…Animal experiments have shown that the abnormal accumulation of formaldehyde promotes Aβ deposition, a main characteristic of AD [52][53][54] in addition to the neurofibrillary tangles [27,55,56] , and induces memory decline and cognitive impairment [12,26] . Therefore, elevation of endogenous formaldehyde may be one of the important risk factors for sporadic AD during aging [57] .…”

“…shown that the human body generates and degrades endogenous formaldehyde [6] , and excessive endogenous formaldehyde leads to neurodegenerative diseases [7][8][9][10][11][12] .…”

Early multidomain intervention to stave off Alzheimer’s disease

“…甲 醛 参 与 DNA 、 RNA、 组蛋白等甲基化 [27] . 因此, 甲醛代谢失调, 可以 通过影响表观遗传学, 以及蛋白质的异常修饰和分子 聚集, 从而造成包括学习记忆在内的认知损伤 [28,29] .…”

The early intervention of geniposide and PNS combination modulated Aβ production and synaptic plasticity in young APP/PS1 transgenic mice

“…PNS is the main bioactive ingredient of Panax notoginseng, which is considered as activating blood circulation to dissipate stasis [4,5]. In vivo, the combination improved spatial learning and memory and recued amyloid plaques in several AD-like animal models [1,6,7,8]; in vitro, GP and PNS showed to protect neuronal damage caused by formaldehyde [9,10] and promoted the neurite outgrowth of rat hippocampal neurons under oxygen/glucose-deprivation conditions [11]. These data suggest that GP and PNS combination undergoes a potential role of neuroprotection in AD.…”