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Standardized Herbal Formula PM012 Decreases Cognitive Impairment and Promotes Neurogenesis in the 3xTg AD Mouse Model of Alzheimer’s Disease

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Abstract

Alzheimer’s disease (AD) is a severe neurodegenerative disease for which there is currently no effective treatment. 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 immunohistochemistry. Neurogenesis was assessed by quantitative labeling with the DNA marker bromodeoxyuridine (BrdU) and the newborn neuron marker doublecortin (DCX). PM012 treatment significantly 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 significantly 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.

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Acknowledgments

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (Ministry of Education, Science, and Technology, MEST) (no. 2007–0054931) and a grant of the Traditional Korean Medicine R&D Project, Ministry for Health and Welfare and Family Affairs, Republic of Korea (B110025).

Conflict of Interest

The authors declare that they have no competing interests.

Authors’ Contributions

MY, JSK, SC, IS, and HB contributed to the conception and design of the study. MY, HSC, YHA, SL, WC, ARY, JSK, MK, and SC performed the experiments and analyzed the data. MY, HSC, and HB wrote the manuscript. All authors read and approved the final manuscript.

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Authors and Affiliations

  1. Department of Physiology, College of Korean Medicine, Kyung Hee University, #1, Hoegi-dong, Dongdaemoon-ku, Seoul, 130-701, Republic of Korea

    Minsook Ye, Su-jin Lim, Won Choi, Manho Kang & Hyunsu Bae

  2. Korean Medicine (KM)-Application Center, Korea Institute of Oriental Medicine (KIOM), 70, Cheomdan-ro, Dong-gu, Daegu, 41062, Republic of Korea

    Hwan-Suck Chung & Insop Shim

  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

    Yong Ho An

  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

    A. Ram Yu & Jin Su Kim

  5. Hospital of Korean Medicine Kyung Hee University Medical Center, #1 Hoegi-dong, Dongdaemoon-ku, Seoul, 130-701, Republic of Korea

    Seunghun Cho

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  1. Minsook Ye
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Ye, M., Chung, HS., An, Y.H. et al. Standardized Herbal Formula PM012 Decreases Cognitive Impairment and Promotes Neurogenesis in the 3xTg AD Mouse Model of Alzheimer’s Disease. Mol Neurobiol 53, 5401–5412 (2016). https://doi.org/10.1007/s12035-015-9458-x

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