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

Objective 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. Methods 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. Results 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. Conclusions 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.