Beilei Chen1,2,3, Yuanyuan Zhao2,3, Wei Li2,3, Jing Hang1,2, Mengmei Yin1,2, Hailong Yu1,2,4. 1. Clinical Medical College of Yangzhou University, Yangzhou 225009, China. 2. Department of Neurology, Northern Jiangsu People's Hospital, Yangzhou 225001, China. 3. Dalian Medical University, Dalian 116044, China. 4. Affiliated of Drum Tower Hospital, Medical school of Nanjing University, Nanjing 210008, China.
Abstract
BACKGROUND: Echinocystic acid (EA), a natural extract from plants of Gleditsia sinensis Lam, exhibits anti-inflammatory, antioxidant and analgesic activities in different diseases. In this study, we explored the pharmacological effects of EA on intracerebral haemorrhage (ICH) in a collagenase-induced ICH mouse model. METHODS: EA (50 mg/kg, i.p. q.d) was injected after the establishment of ICH, and we measured the amount of degraded neurons in brain tissue with Fluoro-Jade C staining and the haemorrhagic injury volume with Luxol fast blue staining on day 3 after ICH. We also assessed animal behaviour by rotarod test, claw force test and modified neurological severity score (mNSS) score. The expression of apoptosis-related proteins such as Bcl-2, Bax and cleaved caspase-3 was analysed by Western blot. RESULTS: EA reduced both the death of neurons and the volume of haemorrhagic injury after ICH. The haemorrhage infarct volume of the ICH+EA group was 9.84%±3.32% lower than that in the ICH group of mice (P<0.01). The mNSS score of the ICH+EA treated group was 4.75±0.55 lower than that in the ICH group (P<0.01). With the administration of EA after ICH, the expression of Bcl-2 was upregulated while the Bax level was downregulated. The cleaved caspase-3 level was also significantly decreased. We further investigated the neuroprotective mechanism of EA. Western blot results showed that the expression of P-AKT increased after EA treatment and decreased after LY294002, an inhibitor of the PI3K/AKT pathway, treatment. CONCLUSIONS: EA may provide neuroprotection via activation of the PI3K/AKT pathway. Given the safety of EA has been proven, further studies are required to investigate whether EA is a potential agent for the treatment of ICH. 2020 Annals of Translational Medicine. All rights reserved.
BACKGROUND: Echinocystic acid (EA), a natural extract from plants of Gleditsia sinensis Lam, exhibits anti-inflammatory, antioxidant and analgesic activities in different diseases. In this study, we explored the pharmacological effects of EA on intracerebral haemorrhage (ICH) in a collagenase-induced ICH mouse model. METHODS: EA (50 mg/kg, i.p. q.d) was injected after the establishment of ICH, and we measured the amount of degraded neurons in brain tissue with Fluoro-Jade C staining and the haemorrhagic injury volume with Luxol fast blue staining on day 3 after ICH. We also assessed animal behaviour by rotarod test, claw force test and modified neurological severity score (mNSS) score. The expression of apoptosis-related proteins such as Bcl-2, Bax and cleaved caspase-3 was analysed by Western blot. RESULTS: EA reduced both the death of neurons and the volume of haemorrhagic injury after ICH. The haemorrhage infarct volume of the ICH+EA group was 9.84%±3.32% lower than that in the ICH group of mice (P<0.01). The mNSS score of the ICH+EA treated group was 4.75±0.55 lower than that in the ICH group (P<0.01). With the administration of EA after ICH, the expression of Bcl-2 was upregulated while the Bax level was downregulated. The cleaved caspase-3 level was also significantly decreased. We further investigated the neuroprotective mechanism of EA. Western blot results showed that the expression of P-AKT increased after EA treatment and decreased after LY294002, an inhibitor of the PI3K/AKT pathway, treatment. CONCLUSIONS: EA may provide neuroprotection via activation of the PI3K/AKT pathway. Given the safety of EA has been proven, further studies are required to investigate whether EA is a potential agent for the treatment of ICH. 2020 Annals of Translational Medicine. All rights reserved.
Authors: Pengfei Li; Tao Tang; Tao Liu; Jing Zhou; Hanjin Cui; Zehui He; Yuanyuan Zhong; En Hu; Ali Yang; Gaohui Wei; Jiekun Luo; Yang Wang Journal: Int J Biol Sci Date: 2019-03-01 Impact factor: 6.580