Cerebroprotein hydrolysate oral liquid alleviates ischemic stroke through improving lipid metabolism abnormalities
10.16438/j.0513-4870.2024-0636
- VernacularTitle:脑多肽口服液通过改善脂质代谢异常发挥对缺血性脑卒中的治疗作用
- Author:
Teng-jie YU
1
;
Ting-ting ZHANG
1
;
Ye LIU
1
;
Dong CHENG
2
;
Hao-yu AI
1
;
Nan JIA
1
;
Lin XIE
1
;
Guang-ji WANG
1
;
Yan LIANG
1
Author Information
1. State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing
2. Jiangsu Institute for Food and Drug Control, Nanjing
- Publication Type:Research Article
- Keywords:
ischemic stroke;
cerebroprotein hydrolysate oral liquid;
lipidomics;
ceramide;
italic>N-acylsphingosine amidohydrolase 1
- From:
Acta Pharmaceutica Sinica
2024;59(11):3117-3129
- CountryChina
- Language:Chinese
-
Abstract:
Cerebroprotein hydrolysate oral liquid (COL) is a neuroprotective preparation composed of various amino acids and peptides, which has beneficial effects on diverse central system diseases. However, the therapeutic effect and potential mechanism of oral COL on ischemic stroke (IS) still need to be explored. This study aims to investigate the therapeutic effects and underlying mechanisms of COL on IS in vivo and in vitro. An IS rat model was established through middle cerebral artery occlusion (MCAO) surgery, and triphenyltetrazolium chloride (TTC) staining, behavioral scoring, Evans blue leakage, enzyme-linked immunosorbent assay (ELISA) and immunofluorescence staining were performed to investigate the effects of COL on cerebral infarct size, neurological function, blood-brain barrier (BBB) and neuroinflammation in IS rats. An in vitro model of IS was established on hCMEC/D3 cells through oxygen-glucose deprivation/reperfusion (OGD/R), and cell counting kit-8 assay, reactive oxygen species (ROS) detection, scratch test and Transwell test were conducted to examine the influence of COL on cell viability, oxidative stress and migration ability. Lipidomics technology, real-time quantitative PCR and Western blot experiments were used to investigate the regulation and mechanism of COL on lipid metabolism in the brain of IS rats. All the animal experiments were approved by Ethical Committee of Animal Experiments of China Pharmaceutical University (No.2022-02-23). Our results showed that intragastric administration of COL could significantly reduce the area of cerebral infarction, improve neurological deficits, lower the levels of inflammatory factors, and protect against the blood-brain barrier damage of rats with IS. OGD/R modeling resulted in a significant decrease in the viability, an elevation in intracellular ROS levels, and a weakened cell migration ability of hCMEC/D3 cells. COL treatment could effectively protect hCMEC/D3 cells from damage caused by OGD/R. More importantly, cerebral ischemia led to significant lipid metabolism disorders in the brain of rats, and significant accumulation of intracerebral triglycerides (TAG) and ceramides (Cer) was observed in IS rats. COL was proved to significantly reverse lipid metabolism disorders in the brain of IS rats and reduce the content of cytotoxic lipid Cer by upregulating the intracerebral levels of an acid ceramidase called N-acylsphingosine amidehydrolase 1 (ASAH1). In summary, COL was proved to be a promising and effective candidate for IS treatment, which could alleviate cerebral ischemic injury by regulating abnormal lipid metabolism.
