Standardized Herbal Formula PM012 Decreases Cognitive Impairment and Promotes Neurogenesis in the 3xTg AD Mouse Model of Alzheimer’ s Disease Minsook Ye 1 & Hwan-Suck Chung 2 & Yong Ho An 3 & Su-jin Lim 1 & Won Choi 1 & A. Ram Yu 4 & Jin Su Kim 4 & Manho Kang 1 & Seunghun Cho 5 & Insop Shim 2 & Hyunsu Bae 1 Received: 14 May 2015 /Accepted: 25 September 2015 # Springer Science+Business Media New York 2015 Abstract Alzheimer’ s disease (AD) is a severe neurodegen- erative disease for which there is currently no effective treat- ment. This study investigated whether treatment with the herbal formula PM012 would improve the cognitive function and the pathological features of AD in 3xTg-AD mice. The cognitive function of 3xTg-AD mice was assessed using the Morris water maze test and positron-emission tomography (PET) with 18 F-2 fluoro-2-deoxy-D-glucose ([F-18] FDG) neuroimaging. The levels of the amyloid beta (Aβ) deposits in the hippocampus were evaluated by immunohistochemis- try. Neurogenesis was assessed by quantitative labeling with the DNA marker bromodeoxyuridine (BrdU) and the newborn neuron marker doublecortin (DCX). PM012 treatment signif- icantly ameliorated memory deficit in AD mice, as shown by shortened escape latencies and increased time spent in the target zone during probe tests. In addition, PM012 significant- ly decreased Aβ deposits, up-regulated the expression of brain-derived neurotrophic factor (BDNF), increased neurogenesis, and improved brain glucose metabolism in the 3xTg-AD mice. These results suggest that PM012 could be a promising treatment for AD. Keywords Alzheimer’ s disease . 3xTg AD . PM012 . Neurogenesis . Beta-amyloid . PET Introduction Dementia is a brain disorder that seriously affects a person’ s ability to carry out daily activities. The cause of dementia generally involves primary neurodegenerative disorders, with the most common being Alzheimer’ s disease (AD) [1]. The global prevalence of dementia was approximately 24.2 mil- lion, and approximately 70 % of these cases were attributed to AD [2, 3]. Unfortunately, there are limited treatments for the large population of patients suffering from AD. The mainstay of treatment for the cognitive loss associ- ated with AD has been muscarinic or nicotinic receptor li- gands and acetylcholinesterase (AChE) inhibitors [ 4]. While there is no cure for Alzheimer ’ s disease, there are five prescription drugs approved by the U.S. Food and Drug Administration (FDA) to treat its symptoms. Donepezil, galantamine, rivastigmine, and tacrine are called Bcholinesterase inhibitors.^ These drugs prevent the break- down of a chemical messenger in the brain important for learning and memory. The fifth drug, memantine, regulates the activity of a different chemical messenger in the brain that is also important for learning and memory [ 5, 6]. However, these drugs have unwanted side effects, such as * Hyunsu Bae hbae@khu.ac.kr 1 Department of Physiology, College of Korean Medicine, Kyung Hee University, #1, Hoegi-dong, Dongdaemoon-ku, Seoul 130-701, Republic of Korea 2 Korean Medicine (KM)-Application Center, Korea Institute of Oriental Medicine (KIOM), 70, Cheomdan-ro, Dong-gu, Daegu 41062, Republic of Korea 3 Acupuncture and Meridian Science Research Center, College of Korean Medical Science Graduate School, Kyung Hee University, #1 Hoegi-dong, Dongdaemoon-ku, Seoul 130-701, Republic of Korea 4 Molecular Imaging Research Center, Korea Institute of Radiological & Medical Sciences University of Science & Technology, #215-4 Gongneug-dong, Nowon-ku, Seoul 139-241, Republic of Korea 5 Hospital of Korean Medicine Kyung Hee University Medical Center, #1 Hoegi-dong, Dongdaemoon-ku, Seoul 130-701, Republic of Korea Mol Neurobiol DOI 10.1007/s12035-015-9458-x