FA-97, a New Synthetic Caffeic Acid Phenethyl Ester Derivative, Protects against Oxidative Stress-Mediated Neuronal Cell Apoptosis and Scopolamine-Induced Cognitive Impairment by Activating Nrf2/HO-1 Signaling

Wan, Ting1,2; Wang, Zihao3,4; Luo, Yi1,2; Zhang, Yifan1,2; He, Wei1,2; Mei, Yu1,2; Xue, Jincheng1,2; Li, Min5; Pan, Huafeng1,2; Li, Weirong1,2; Wang, Qi1,2; Huang, Yujie1,2

2019

10.1155/2019/8239642

Oxidative Medicine and Cellular Longevity   影响因子和分区

19420994

1942-0994

Alzheimer's disease (AD) is an age-related neurodegenerative disorder with cognitive deficits, which is becoming markedly more common in the world. Currently, the exact cause of AD is still unclear, and no curative therapy is available for preventing or mitigating the disease progression. Caffeic acid phenethyl ester (CAPE), a natural phenolic compound derived from honeybee hive propolis, has been reported as a potential therapeutic agent against AD, while its application is limited due to the low water solubility and poor bioavailability. Here, caffeic acid phenethyl ester 4-O-glucoside (FA-97) is synthesized. We validate that FA-97 attenuates H2O2-induced apoptosis in SH-SY5Y and PC12 cells and suppresses H2O2-induced oxidative stress by inhibiting the ROS level, malondialdehyde (MDA) level, and protein carbonylation level, as well as induces cellular glutathione (GSH) and superoxide dismutase (SOD). Mechanistically, FA-97 promotes the nuclear translocation and transcriptional activity of Nrf2 associated with the upregulated expression of HO-1 and NQO-1. The prime importance of Nrf2 activation in the neuroprotective and antioxidant effects of FA-97 is verified by Nrf2 siRNA transfection. In addition, FA-97 prevents scopolamine- (SCOP-) induced learning and memory impairments in vivo via reducing neuronal apoptosis and protecting against cholinergic system dysfunction in the hippocampus and cortex. Moreover, the increased MDA level and low total antioxidant capacity in SCOP-treated mouse brains are reversed by FA-97, with the increased expression of HO-1, NQO-1, and nuclear Nrf2. In conclusion, FA-97 protects against oxidative stress-mediated neuronal cell apoptosis and SCOP-induced cognitive impairment by activating Nrf2/HO-1 signaling, which might be developed as a therapeutic drug for AD.
© 2019 Ting Wan et al.

SCI ; EI

英语

其他

Guangzhou Science, Technology and Innovation Commission[201805010005 201803010047]

Cell Biology

Cell Biology

WOS:000503770300001

Hindawi Limited, 410 Park Avenue, 15th Floor, 287 pmb, New York, NY 10022, United States

20195207930662

Antioxidants ; Carbonylation ; Cell death ; Chemical activation ; Disease control ; Enzymes ; Esters ; Neurodegenerative diseases ; Neurons ; Oxidative stress

Bioengineering and Biology:461 ; Chemical Reactions:802.2 ; Organic Compounds:804.1

Web of Science

1.Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou; 510405, China
2.Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong; 510006, China
3.Institute of Brain and Gut Axis (IBAG), Centre of Clinical Research for Chinese Medicine, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong
4.Department of Chemistry, Southern University of Science and Technology, Shenzhen, Guangdong; 518055, China
5.Clinical Medical College of Acupuncture Moxibustion and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong; 510006, China

Wan, Ting,Wang, Zihao,Luo, Yi,et al. FA-97, a New Synthetic Caffeic Acid Phenethyl Ester Derivative, Protects against Oxidative Stress-Mediated Neuronal Cell Apoptosis and Scopolamine-Induced Cognitive Impairment by Activating Nrf2/HO-1 Signaling[J]. Oxidative Medicine and Cellular Longevity,2019,2019.

Wan, Ting.,Wang, Zihao.,Luo, Yi.,Zhang, Yifan.,He, Wei.,...&Huang, Yujie.(2019).FA-97, a New Synthetic Caffeic Acid Phenethyl Ester Derivative, Protects against Oxidative Stress-Mediated Neuronal Cell Apoptosis and Scopolamine-Induced Cognitive Impairment by Activating Nrf2/HO-1 Signaling.Oxidative Medicine and Cellular Longevity,2019.

Wan, Ting,et al."FA-97, a New Synthetic Caffeic Acid Phenethyl Ester Derivative, Protects against Oxidative Stress-Mediated Neuronal Cell Apoptosis and Scopolamine-Induced Cognitive Impairment by Activating Nrf2/HO-1 Signaling".Oxidative Medicine and Cellular Longevity 2019(2019).