NeuroProtect, a Candidate Formula From Traditional Chinese Medicine, Attenuates Amyloid-ß and Restores Synaptic Structures in APP/PS1 Transgenic Mice.

Background: Alzheimer's disease (AD) is the most common cause of dementia. The emerging data suggest that cognitive decline occurred in the setting of Aß accumulation with synaptic dysfunction, which started to happen at preclinical stages. Then, presymptomatic intervention is more critical to postponing AD processing. Traditional Chinese medicine has a long history of treating and preventing dementia. Findings have shown that the decoction of Panax notoginseng and Gardenia jasminoides Ellis enhances memory functions in patients with stroke, and their main components, Panax notoginseng saponins (PNS) and geniposide (GP), improved memory abilities in experimental AD models. Since herbal medicine has advantages in protection with few side effects, we wish to extend observations of the NeuroProtect (NP) formulation for reducing amyloid-ß and restoring synaptic structures in APP/PS1 transgenic mice. Methods: APP/PS1 transgenic mice and their wild-type littermates were fed with control, NP, and their components from 4 to 7 months of age. We assessed the synaptic structure by Golgi staining, analyzed the amyloid deposits by Thioflavin-S staining, and measured related protein levels by Western blot or ELISA. We used the Morris water maze and shuttle box test to evaluate cognitive functions. Results: Compared to WT mice, APP/PS1 mice are characterized by the accumulation of amyloid plaques, reducing synaptic structure richness and memory deficits. NP prevents these changes and ameliorates cognitive deficits. These effects may have been due to the contribution of its components by inhibition of insoluble amyloid-ß deposition and restoration of synaptic structures. Conclusion: These findings reveal a beneficial effect of NP on AD progression under an early intervention strategy and provide a food supplement for AD prevention.

Hypomagnetic fields cause anxiety in adult male mice.

Hypomagnetic fields (HMF), that is, the elimination of the geomagnetic field (GMF), are a risk factor to the health of astronauts in outer space. It has been established that continuous HMF exposure affects cytoskeleton assembly, cell proliferation, embryonic development, and even learning and memory. In addition, although there were some previous studies that focused on the effects of long-term HMF-exposure, so far very limited investigations have been conducted to examine the short-term HMF effect in animals. In this study, we exposed adult male C57BL/6 mice to a 3-axis Helmholtz-coil HMF-simulation system for 72 h and found that short-term HMF-exposure induced a significant increase in anxiety-related behaviors. And our findings provide important information for both psychological intervention and the health care of astronauts. Bioelectromagnetics. 40:27-32, 2019. © 2018 Wiley Periodicals, Inc.

Neuroprotective effects of geniposide in SH-SY5Y cells and primary hippocampal neurons exposed to Aß42.

Our former studies have suggested that TongLuoJiuNao (TLJN) is clinically efficacious in the treatment of dementia and improving learning and memory in AD models. When Aß aggregated with oligomer, it is known to be able to induce cellular toxicity as well as cognitive impairment. We tested the possibility that TLJN affects the formation of Aß oligomers. In our experiment, TLJN improved cell viability, inhibited LDH release, and promoted the outgrowth of neurites of neurons treated with Aß. Geniposide, the main component of TLJN, could increase the cell viability of SY5Y-APP695sw cells. The cytotoxicity of pretreated Aß with geniposide was decreased in a dose-dependent manner. SDS-PAGE and Western blotting showed that geniposide and TLJN stimulated Aß oligomer assembly. Compared with the control, more and longer fibrils of Aß in the presence of geniposide were observed under electron microscope though the fibrils became less sensitive to thioflavin T staining. In sum, geniposide is able to protect neurons from Aß-induced damage by remodeling Aß.

Geniposide, the component of the Chinese herbal formula Tongluojiunao, protects amyloid-ß peptide (1-42-mediated death of hippocampal neurons via the non-classical estrogen signaling pathway.

Tongluojiunao (TLJN) is an herbal medicine consisting of two main components, geniposide and ginsenoside Rg1. TLJN has been shown to protect primary cultured hippocampal neurons. However, its mechanism of action remains unclear. In the present study, primary cultured hippocampal neurons treated with Aß1-42 (10 µmol/L) significantly increased the release of lactate dehydrogenase, which was markedly reduced by TLJN (2 µL/mL), specifically by the component geniposide (26 µmol/L), but not ginsenoside Rg1 (2.5 µmol/L). The estrogen receptor inhibitor, ICI182780 (1 µmol/L), did not block TLJN- or geniposide-mediated decrease of lactate dehydrogenase under Aß1-42-exposed conditions. However, the phosphatidyl inositol 3-kinase or mitogen-activated protein kinase pathway inhibitor, LY294002 (50 µmol/L) or U0126 (10 µmol/L), respectively blocked the decrease of lactate dehydrogenase mediated by TLJN or geniposide. Therefore, these results suggest that the non-classical estrogen pathway (i.e., phosphatidyl inositol 3-kinase or mitogen-activated protein kinase) is involved in the neuroprotective effect of TLJN, specifically its component, geniposide, against Aß1-42-mediated cell death in primary cultured hippocampal neurons.