Multiplex Brain Proteomic Analysis Revealed the Molecular Therapeutic Effects of Buyang Huanwu Decoction on Cerebral Ischemic Stroke Mice.
Stroke is the second-leading cause of death worldwide, and tissue plasminogen activator (TPA) is the only drug used for a limited group of stroke patients in the acute phase. Buyang Huanwu Decoction (BHD), a traditional Chinese medicine prescription, has long been used for improving neurological functional recovery in stroke. In this study, we characterized the therapeutic effect of TPA and BHD in a cerebral ischemia/reperfusion (CIR) injury mouse model using multiplex proteomics approach. After the iTRAQ-based proteomics analysis, 1310 proteins were identified from the mouse brain with <1% false discovery rate. Among them, 877 quantitative proteins, 10.26% (90/877), 1.71% (15/877), and 2.62% (23/877) of the proteins was significantly changed in the CIR, BHD treatment, and TPA treatment, respectively. Functional categorization analysis showed that BHD treatment preserved the integrity of the blood-brain barrier (BBB) (Alb, Fga, and Trf), suppressed excitotoxicity (Grm5, Gnai, and Gdi), and enhanced energy metabolism (Bdh), thereby revealing its multiple effects on ischemic stroke mice. Moreover, the neurogenesis marker doublecortin was upregulated, and the activity of glycogen synthase kinase 3 (GSK-3) and Tau was inhibited, which represented the neuroprotective effects. However, TPA treatment deteriorated BBB breakdown. This study highlights the potential of BHD in clinical applications for ischemic stroke.
National Research Institute of Chinese Medicine, Taipei, Taiwan; Institute of Food Science and Technology, National Taiwan University, Taipei, Taiwan.
Hong-Jhang
HJ
Chen
National Research Institute of Chinese Medicine, Taipei, Taiwan.
Yuh-Chiang
YC
Shen
National Research Institute of Chinese Medicine, Taipei, Taiwan.
Young-Ji
YJ
Shiao
Department of Chinese Martial Arts and Graduate Institute of Sport Coaching Science, Chinese Culture University, Taipei, Taiwan.
Kuo-Tong
KT
Liou
National Research Institute of Chinese Medicine, Taipei, Taiwan.
Wei-Hsiang
WH
Hsu
Agricultural Biotechnology Research Center, Academia Sinica, Taipei, Taiwan.
Pei-Hsuan
PH
Hsieh
Agricultural Biotechnology Research Center, Academia Sinica, Taipei, Taiwan.
Chi-Ying
CY
Lee
Agricultural Biotechnology Research Center, Academia Sinica, Taipei, Taiwan.
Yet-Ran
YR
Chen
National Research Institute of Chinese Medicine, Taipei, Taiwan; Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, Taichung, Taiwan; School of Pharmacy, National Taiwan University, Taipei, Taiwan.
Yun-Lian
YL
Lin
D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism*; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism*; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D049268:Positron-Emission Tomography; D040901:Proteomics / Q000379:methods*; D020521:Stroke / Q000188:drug therapy* / Q000378:metabolism*
D004365:Drugs, Chinese Herbal; C460102:buyang huanwu