Protection against acute cerebral ischemia/reperfusion injury by Leonuri Herba Total Alkali via modulation of BDNF-TrKB-PI3K/Akt signaling pathway in rats

• Published in: Biomedicine & pharmacotherapy 2021-01, Vol.133, p.111021-111021, Article 111021
• Main Authors: Li, Yan, Xiang, Liling, Wang, Can, Song, Yagang, Miao, Jinxin, Miao, Mingsan
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis Regulatory Proteins - metabolism; BDNF; Brain - drug effects; Brain - enzymology; Brain - pathology; Brain-Derived Neurotrophic Factor - metabolism; Cerebral ischemia; Disease Models, Animal; Drugs, Chinese Herbal - pharmacology; Infarction, Middle Cerebral Artery - drug therapy; Infarction, Middle Cerebral Artery - enzymology; Infarction, Middle Cerebral Artery - pathology; Inflammatory cytokines; Leonuri Herba Total Alkali; Leonurus - chemistry; Male; Neurons - drug effects; Neurons - enzymology; Neurons - pathology; Neuroprotective Agents - pharmacology; Phosphatidylinositol 3-Kinase - metabolism; Phosphorylation; PI3K/Akt pathway; Proto-Oncogene Proteins c-akt - metabolism; Rats; Rats, Sprague-Dawley; Receptor, trkB - metabolism; Reperfusion Injury - enzymology; Reperfusion Injury - pathology; Reperfusion Injury - prevention & control; Signal Transduction
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2020.111021

[Display omitted] •Pretreatment with Leonuri Herba Total Alkali (LHA) for a certain period of time significantly enhanced the prevention mechanism against acute cerebral ischemia reperfusion.•Pretreatment with LHA can also suppressed inflammatory response in rats with acute cerebral ischemia reperfusion.•The mechanisms of LHA against acute cerebral ischemia might be associated with regulate the PI3K/Akt pathway by increasing BDNF levels. To observe the brain protective effect of Leonuri Herba Total Alkali (LHA) on cerebral ischemia reperfusion injury in rats, so as to provide basis for clinical research. Adult male SD rats were randomly assigned into sham group, middle cerebral artery occlusion/reperfusion (MCAO/R) group, and LHA + MCAO/R group (25 mg/kg, 50 mg/kg, and 100 mg/kg). Fourteen days before MCAO/R surgery, the rats in treatment groups were orally administered with LHA in ultrapure water once daily for 14 days, while rats in the sham and MCAO groups were given the same amount of saline in advance. After 1 h of administration on the 14th day, MCAO surgery was subjected. The neurological deficits, brain infarct volume, histopathology, immunofluorescence, inflammation indicators and the gene/protein expressions of BDNF-TrKB-PI3K/Akt signaling pathway in the rat brain tissue were evaluated 24 h after the MCAO/R-injury. It was found that rats in LHA pre-administration group showed significantly reduced neurological deficit scores, infarction volume, the serum levels of NSE and S100β. Meanwhile, the content of Evans Blue (EB) in brain tissue from LHA group was decreased, as well as the levels of inflammatory cytokines and their gene levels. Moreover, LHA pre-administration inhibited the expression of CD44, GFAP, FOXO1 and promoted the expression of BDNF and NeuN. In addition, LHA pre-administration could up-regulate the protein expression of TrkB, p-PI3K, p-Akt, Bcl-2, and down-regulate the protein expression of Bax, and increase the level of Bcl-2/Bax. The study demonstrated that LHA pre-administration could regulate the PI3K/Akt pathway by increasing BDNF levels, and play a neuroprotective role in cerebral ischemia-reperfusion injury.