Abstract
BackgroundShen-Zhi-Ling oral liquid (SZL) is an herbal formula known for its efficacy of nourishing “heart and spleen”, and is used for the treatment and prevention of middle- and early-stage dementia. This study investigated the effects of SZL on amelioration of AD, and examined whether the underlying mechanisms from the perspective of neuroprotection are related to brain glucose metabolism.MethodsFirstly, LC–MS/MS was used to analysis the SZL mainly enters the blood component. Then, the effects of SZL on cognitive and behavioral ability of APP/PS1 double transgenic mice and amyloid protein characteristic pathological changes were investigated by behavioral study and morphological observation. The effects of SZL on the ultrastructure of mitochondria, astrocytes, and micrangium related to cerebral glucose metabolism were observed using transmission electron microscopy. Then, micro-PET was also used to observe the effects of SZL on glucose uptake. Furthermore, the effects of SZL on insulin signaling pathway InR/PI3K/Akt and glucose transporters (GLUT1 and GLUT3) were observed by immunohistochemistry, Western-blot and RT-qPCR. Finally, the effects of SZL on brain glucose metabolism and key enzyme were observed. In vitro, the use of PI3K and/or GSK3β inhibitor to observe the effects of SZL drug-containing serum on GLUT1 and GLUT3.ResultsIn vivo, SZL could significantly ameliorate cognitive deficits, retarded the pathological damage, including neuronal degeneration, Aβ peptide aggregation, and ultrastructural damage of hippocampal neurons, improve the glucose uptake, transporters and glucolysis. Beyond that, SZL regulates the insulin signal transduction pathway the insulin signal transduction pathway InR/PI3K/Akt. Furthermore, 15% SZL drug-containing serum increased Aβ42-induced insulin signal transduction-pathway related indicators and GLUT1 and GLUT3 expression in SH-SY5Y cells. The improvement of GLUT1 and GLUT3 in the downstream PI3K/Akt/GSK3β signaling pathway was reversed by the use of PI3K and/or GSK3β inhibitor.ConclusionsIn summary, our results demonstrated that improving glucose uptake, transport, and glycolysis in the brain may underlie the neuroprotective effects of SZL, and its potential molecular mechanism may be related to regulate the insulin signal transduction pathway.
Highlights
Alzheimer’s disease (AD), the most prevalent form of dementia, is characterized by beta-amyloid (Aβ) plaque deposition and neurofibrillary tangles of hyperphosphorylated tau protein [1]
In summary, our results demonstrated that improving glucose uptake, transport, and glycolysis in the brain may underlie the neuroprotective effects of Shen-Zhi-Ling oral liquid (SZL), and its potential molecular mechanism may be related to regulate the insulin signal transduction pathway
Impairment of brain glucose metabolism is a pathophysiological feature of AD that occurs before cognitive dysfunction and pathological changes [3, 4]
Summary
Alzheimer’s disease (AD), the most prevalent form of dementia, is characterized by beta-amyloid (Aβ) plaque deposition and neurofibrillary tangles of hyperphosphorylated tau protein [1]. Impairment of brain glucose metabolism is a pathophysiological feature of AD that occurs before cognitive dysfunction and pathological changes [3, 4]. Studies have shown that the imbalance of glucose metabolism homeostasis in the brain, which is closely related to defects in the insulin signaling pathway Insulin-like receptor/phosphoinositide 3-kinase/protein kinase B (InR/PI3K/Akt), plays an important role in the early onset of AD [3, 4]. The mechanisms underlying the characteristic pathological changes of Aβ plaques and neurofibrillary tangles in early AD is still unclear. Some research has suggested that changes in cerebral glucose metabolism is the upstream trigger factor [7]. This study investigated the effects of SZL on amelioration of AD, and examined whether the underlying mechanisms from the perspective of neuroprotection are related to brain glucose metabolism
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call