Research Article Neuroprotective Effects of the Herbal Formula B401 in Both Cell and Mouse Models of Alzheimer’s Disease Chih-Hsiang Hsu, 1 Sheue-Er Wang, 2 Ching-Lung Lin, 1 Chun-Jen Hsiao, 1 Shuenn-Jyi Sheu, 3 and Chung-Hsin Wu 1 1 Department of Life Sciences, National Taiwan Normal University, Taipei City, Taiwan 2 Department of Pathological Inspection, Saint Paul’s Hospital, Taoyuan City, Taiwan 3 Brion Research Institute of Taiwan, New Taipei City, Taiwan Correspondence should be addressed to Chung-Hsin Wu; megawu@ntnu.edu.tw Received 6 May 2016; Accepted 26 July 2016 Academic Editor: Jian-Li Gao Copyright © 2016 Chih-Hsiang Hsu et al. Tis is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. In this study, we have reported the herbal formula B401 that has neuroprotective efects via multifunction, multitarget characteristics. It is possible that the herbal formula B401 may also provide new insights for AD. Here, we studied protective efects in the Tet-On A 42 -GFP SH-SY5Y cell model and the APP/PS1/Tau triple transgenic mouse model by the herbal formula B401. In in vitro experiments, we showed that the herbal formula B401 treatment efectively reduces glutamate-induced excitotoxicity and acetylcholinesterase activity in Tet-On A 42 -GFP SH-SY5Y cells. In in vivo experiments, we found that oral B401 treatment efectively ameliorates neurocognitive dysfunctions of 3× Tg-AD mice via motor and cognitive behavior tests. By using magnetic resonance imaging, moorFLPI instruments, and chemiluminescence methods, we reported that oral B401 treatment efectively alleviates brain atrophy, improves subcutaneous blood fow, and reduces blood ROS in 3× Tg-AD mice. As observed from results of immunohistochemistry staining and western blotting, we found that oral B401 treatment signifcantly enhances expressions of neuroprotective proteins, while reducing expressions of AD derived proteins such as amyloid beta, phosphorylated Tau, neurofbrillary tangles, and 3-nitrotyrosine in the brain of3× Tg-AD mice. Tus, the herbal formula B401 may have the potential to be developed into optimum TCM for AD patients. 1. Introduction Alzheimer’s disease (AD) is a chronic neurodegenerative disease with obvious memory loss. AD hallmarks such as amyloid plaques and neurofbrillary tangles (NFTs) are obvi- ously found in the brains of AD patients [1, 2]. Te amyloid plaques are abnormal clusters of dead nerve cells and beta amyloid (A) proteins, while the NFTs are twisted protein fragments inside the nerve cells. Tese amyloid plaques and NFTs prevent neurons from communicating with other neurons and hence cause the cognitive defcits in the brain. Intracellular A aggregation leads to the hyperphospho- rylation of Tau, the disruption of mitochondria function, and the synapse dysfunction [3–6]. In addition, NFTs are abnormal heaps of phosphorylated Tau proteins [7]. Tau pro- tein is a soluble microtubule-binding protein that can attach and stabilize microtubules contributing to axonal transport and neurite outgrowth [8, 9]. In addition, Tau is hyperphos- phorylated leading to its detachment from microtubules and subsequently the formation of soluble Tau aggregates and NFTs [10]. AD patients are clinically diagnosed with a progression from episodic memory and learning ability defcits to the decline of cognitive function and have average 9 years of life span afer diagnosis [11, 12]. Te conventional therapy for mild to moderate AD symptoms is the treatment with AChE inhibitors such as memantine to have better cognitive func- tion [13, 14]. It is possible that decreasing acetylcholine level in AD brain may lead to cognitive impairment [15–17]. Acetyl- cholinesterase (AChE) is an enzyme that catalyzes acetyl- choline hydrolysis and is mainly found at cholinergic brain synapses and neuromuscular junctions to terminate synaptic Hindawi Publishing Corporation Evidence-Based Complementary and Alternative Medicine Volume 2016, Article ID 1939052, 17 pages http://dx.doi.org/10.1155/2016/1939052