Antidepressant effects of 3-(3,4-methylenedioxy-5-trifluoromethyl phenyl)-2E-propenoic acid isobutyl amide involve TSPO-mediated mitophagy signalling pathway
Wangyi Zhou
Pharmacology and Toxicology Research Centre, Tasly Institute, Tasly Holding Group Co., Ltd., Tianjin, China
Search for more papers by this authorJi Zheng
Department of Pharmacology, Institute of Basic Medical Sciences, Neuroscience Center, Chinese Academy of Medical Sciences & School of Basic Medicine, Peking Union Medical College, Beijing, China
Search for more papers by this authorDongmei Li
Department of Pharmacology, Institute of Basic Medical Sciences, Neuroscience Center, Chinese Academy of Medical Sciences & School of Basic Medicine, Peking Union Medical College, Beijing, China
Search for more papers by this authorMingyang Wang
Department of Pharmacology, Institute of Basic Medical Sciences, Neuroscience Center, Chinese Academy of Medical Sciences & School of Basic Medicine, Peking Union Medical College, Beijing, China
Search for more papers by this authorLu Feng
Department of Pharmacology, Institute of Basic Medical Sciences, Neuroscience Center, Chinese Academy of Medical Sciences & School of Basic Medicine, Peking Union Medical College, Beijing, China
Search for more papers by this authorWei Huang
Department of Pharmacology, Institute of Basic Medical Sciences, Neuroscience Center, Chinese Academy of Medical Sciences & School of Basic Medicine, Peking Union Medical College, Beijing, China
Search for more papers by this authorNan Yang
Department of Pharmacology, Institute of Basic Medical Sciences, Neuroscience Center, Chinese Academy of Medical Sciences & School of Basic Medicine, Peking Union Medical College, Beijing, China
Search for more papers by this authorMin Han
Pharmacology and Toxicology Research Centre, Tasly Institute, Tasly Holding Group Co., Ltd., Tianjin, China
Search for more papers by this authorCorresponding Author
Xiaohui Ma
Pharmacology and Toxicology Research Centre, Tasly Institute, Tasly Holding Group Co., Ltd., Tianjin, China
Correspondence
Yanyong Liu, Medical College, Tibet University, Tibet Autonomous Region, Lhasa, 850000, China; Department of Pharmacology, Institute of Basic Medical Sciences, Center of Neuroscience, Chinese Academy of Medical Sciences & School of Basic Medicine, Peking Union Medical College, 5 Dong Dan San Tiao, Beijing 100005, China.
Email: [email protected]
Xiaohui Ma, Pharmacology and Toxicology Research Centre, Tasly Institute, Tasly Holding Group Co., Ltd., 2 East Pu Ji He Road, Beichen District, Tianjin 300410, China.
Email: [email protected]
Search for more papers by this authorCorresponding Author
Yanyong Liu
Medical College, Tibet University, Lhasa, China
Department of Pharmacology, Institute of Basic Medical Sciences, Neuroscience Center, Chinese Academy of Medical Sciences & School of Basic Medicine, Peking Union Medical College, Beijing, China
Correspondence
Yanyong Liu, Medical College, Tibet University, Tibet Autonomous Region, Lhasa, 850000, China; Department of Pharmacology, Institute of Basic Medical Sciences, Center of Neuroscience, Chinese Academy of Medical Sciences & School of Basic Medicine, Peking Union Medical College, 5 Dong Dan San Tiao, Beijing 100005, China.
Email: [email protected]
Xiaohui Ma, Pharmacology and Toxicology Research Centre, Tasly Institute, Tasly Holding Group Co., Ltd., 2 East Pu Ji He Road, Beichen District, Tianjin 300410, China.
Email: [email protected]
Search for more papers by this authorWangyi Zhou
Pharmacology and Toxicology Research Centre, Tasly Institute, Tasly Holding Group Co., Ltd., Tianjin, China
Search for more papers by this authorJi Zheng
Department of Pharmacology, Institute of Basic Medical Sciences, Neuroscience Center, Chinese Academy of Medical Sciences & School of Basic Medicine, Peking Union Medical College, Beijing, China
Search for more papers by this authorDongmei Li
Department of Pharmacology, Institute of Basic Medical Sciences, Neuroscience Center, Chinese Academy of Medical Sciences & School of Basic Medicine, Peking Union Medical College, Beijing, China
Search for more papers by this authorMingyang Wang
Department of Pharmacology, Institute of Basic Medical Sciences, Neuroscience Center, Chinese Academy of Medical Sciences & School of Basic Medicine, Peking Union Medical College, Beijing, China
Search for more papers by this authorLu Feng
Department of Pharmacology, Institute of Basic Medical Sciences, Neuroscience Center, Chinese Academy of Medical Sciences & School of Basic Medicine, Peking Union Medical College, Beijing, China
Search for more papers by this authorWei Huang
Department of Pharmacology, Institute of Basic Medical Sciences, Neuroscience Center, Chinese Academy of Medical Sciences & School of Basic Medicine, Peking Union Medical College, Beijing, China
Search for more papers by this authorNan Yang
Department of Pharmacology, Institute of Basic Medical Sciences, Neuroscience Center, Chinese Academy of Medical Sciences & School of Basic Medicine, Peking Union Medical College, Beijing, China
Search for more papers by this authorMin Han
Pharmacology and Toxicology Research Centre, Tasly Institute, Tasly Holding Group Co., Ltd., Tianjin, China
Search for more papers by this authorCorresponding Author
Xiaohui Ma
Pharmacology and Toxicology Research Centre, Tasly Institute, Tasly Holding Group Co., Ltd., Tianjin, China
Correspondence
Yanyong Liu, Medical College, Tibet University, Tibet Autonomous Region, Lhasa, 850000, China; Department of Pharmacology, Institute of Basic Medical Sciences, Center of Neuroscience, Chinese Academy of Medical Sciences & School of Basic Medicine, Peking Union Medical College, 5 Dong Dan San Tiao, Beijing 100005, China.
Email: [email protected]
Xiaohui Ma, Pharmacology and Toxicology Research Centre, Tasly Institute, Tasly Holding Group Co., Ltd., 2 East Pu Ji He Road, Beichen District, Tianjin 300410, China.
Email: [email protected]
Search for more papers by this authorCorresponding Author
Yanyong Liu
Medical College, Tibet University, Lhasa, China
Department of Pharmacology, Institute of Basic Medical Sciences, Neuroscience Center, Chinese Academy of Medical Sciences & School of Basic Medicine, Peking Union Medical College, Beijing, China
Correspondence
Yanyong Liu, Medical College, Tibet University, Tibet Autonomous Region, Lhasa, 850000, China; Department of Pharmacology, Institute of Basic Medical Sciences, Center of Neuroscience, Chinese Academy of Medical Sciences & School of Basic Medicine, Peking Union Medical College, 5 Dong Dan San Tiao, Beijing 100005, China.
Email: [email protected]
Xiaohui Ma, Pharmacology and Toxicology Research Centre, Tasly Institute, Tasly Holding Group Co., Ltd., 2 East Pu Ji He Road, Beichen District, Tianjin 300410, China.
Email: [email protected]
Search for more papers by this authorWei and Zhou are contributed equally to this work.
Funding information
This study was supported by Natural Science Foundation of China (81050025) and Foundation from Tianjin Tasly Pharmaceutical Co., Ltd.
Abstract
Piper laetispicum C. DC is one of the Chinese herbal medicines used for alleviating depressive disorders. G11-5 [3-(3, 4-methylenedioxy-5-trifluoromethyl phenyl)-2E-propenoic acid isobutyl amide] is synthesized based on the chemical structure of an active integrant of Piper laetispicum C. DC. The present study assessed the antidepressant effect of G11-5 and investigated the underlying mechanism with learned helplessness (LH) and social defeat stress (SDS) mice model of depression. In the LH model, mice were exposed to 60 inescapable electric shocks once a day for three consecutive days followed by 2-week drug administration and helpless behaviour assessment. In the SDS model, mice were subjected to repeated social defeat by an aggressive CD-1 mouse once a day for consecutive 10 days. Following oral administration for 2 weeks, the mice were subjected to a series of behavioural tests including social interaction test. G11-5 significantly decreased the number of escape failures induced by LH paradigm, meanwhile increased the social interaction ratio and shortened the immobility time in forced swimming test for the SDS-exposed mice, suggesting remarkable antidepressant effect. Moreover, G11-5 ameliorated the changes in mitophagy-related proteins induced by two stress exposures and restored retrograde axonal transport and neurotransmitter release. Our findings suggested that G11-5 exhibited an obvious antidepressant through TSPO-mediated mitophagy pathway.
CONFLICT OF INTEREST
The authors declare that there are no conflicts of interest.
Supporting Information
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