Abstract
BackgroundNeuroinflammation and apoptosis are involved in the pathogenesis of ischaemic stroke. Alisol A 24-acetate (24A) exerts a strong inhibitory effect on inflammation and cell apoptosis. The neuroprotective effect of 24A on global cerebral ischaemia/reperfusion (GCI/R) injury remains unclear.MethodsGCI/R mice were used to investigate the neuroprotective effect of 24A. Modified neurological deficit scores, Morris water maze and object recognition tests were used to evaluate behaviours. Metabolism in brain regions was detected using magnetic resonance spectroscopy (MRS), and changes in microglia, astrocytes and neurons were detected. Inflammation and apoptosis were measured.ResultsThe results showed that 24A suppressed neurological deficits scores and improved GCI/R induced cognitive dysfunction. It was also observed that 24A could alleviate neuroinflammation, which manifested as 24A inhibited microglia and astrocytes proliferation, downregulated the expression of interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and inducible nitric oxide synthase (iNOS) in the GCI/R mice brain. The apoptosis of neurons reduced, and dendritic spines of hippocampal neurons increased in the presence of 24A. In addition, 24A could up-regulate the expression of phosphorylated phosphoinositide 3-kinases (p-PI3K) and phosphorylated protein kinase B (p-AKT) in GCI/R mice brain, and all the morphological, neurological, and biochemical changes of 24A treatment were abolished by the application of PI3K/AKT pathway inhibitor LY294002.ConclusionsTaken together, our study indicated that 24A alleviated GCI/R injury by inhibiting neuroinflammation and apoptosis through the regulation of the PI3K/AKT pathway.
Highlights
Ischaemic stroke results in damage to the brain function by altering the blood supply and induces a series of neurological symptoms, which seriously endanger people’sLu et al Journal of Neuroinflammation (2022) 19:37 of ischaemia–reperfusion (I/R) after ischaemic stroke, and the identification of new treatments is urgently needed.Alisol A 24-acetate (24A), a protostane-type tetracyclic triterpenoid, is one of the main components in Alisma orientale (Sam.) Juz [3, 4]
Neuroinflammation and cell apoptosis are inhibited by activating Phosphatidylinositol 3-kinase (PI3K)/Protein kinase B (AKT) signalling after cerebral ischaemia [11]. These results indicate that the upregulation of the PI3K/AKT pathway exerts a strong neuroprotective effect by reducing neuroinflammation and apoptosis caused by brain I/R injury
24A ameliorated the neurological deficits, and the effect was reversed by the PI3K inhibitor LY294002
Summary
Ischaemic stroke results in damage to the brain function by altering the blood supply and induces a series of neurological symptoms, which seriously endanger people’sLu et al Journal of Neuroinflammation (2022) 19:37 of ischaemia–reperfusion (I/R) after ischaemic stroke, and the identification of new treatments is urgently needed.Alisol A 24-acetate (24A), a protostane-type tetracyclic triterpenoid, is one of the main components in Alisma orientale (Sam.) Juz [3, 4]. Wu et al reported that 24A suppresses oxidative stress and stimulates autophagy through the Adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK)/ mammalian target of rapamycin (mTOR) pathway in mice with nonalcoholic steatohepatitis [5]. Another in vitro study indicated that 24A effectively reduces the levels of inflammatory factors, such as TNF-α, IL-1β, IL-6, and IL-8 in HepG2 cells [6]. The potential neuroprotective role of 24A in ischaemic stroke remains to be elucidated. Neuroinflammation and apoptosis are involved in the pathogenesis of ischaemic stroke. Alisol A 24-acetate (24A) exerts a strong inhibitory effect on inflammation and cell apoptosis. The neuroprotective effect of 24A on global cerebral ischaemia/reperfusion (GCI/R) injury remains unclear
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