Shen-Zhi-Ling oral liquid ameliorates cerebral glucose metabolism disorder in early AD via insulin signal transduction pathway in vivo and in vitro

Abstract

Background Shen-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. Methods Firstly, 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. Results In 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. Conclusions In 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.

Jiedu-Yizhi Formula Improves Cognitive Impairment in an Aβ25–35-Induced Rat Model of Alzheimer’s Disease by Inhibiting Pyroptosis

“…For example, the classic formula Shen-Zhi-Ling Oral Liquid, which is used for the treatment of AD, can reduce APP mRNA expression in the hippocampus, reduce amyloid deposition, reduce Caspase-3 expression, reduce neuronal apoptosis [ 44 , 45 ], and increase hippocampal haemoglobin. The expression of oxygenase-1 (HO-1) and biliverdin reductase (BVR) can resist oxidative damage [ 46 ], regulate the insulin signal transduction pathway INR/PI3K/Akt, and improve glucose uptake, transport, and glycolysis in the brain [ 47 ]. The methods for improving AD are diversified and conform to the various pathological mechanisms of AD, thus achieving good clinical results.…”

Herbal/Natural Compounds Resist Hallmarks of Brain Aging: From Molecular Mechanisms to Therapeutic Strategies

“…Furthermore, rodents with mild cognitive impairment and AD exhibit impaired glucose metabolism resulting from oxidative stress-mediated dysfunction of neuronal glucose transport proteins [ 106 ]. In an in vivo study, the herbal mixture Shenzhiling oral liquid ameliorated hippocampal neuronal degeneration, reduced Aβ peptide aggregation, and improved cellular ultrastructure by modulating insulin signaling pathways and increasing glucose uptake, upregulating glucose transport proteins (GLUT1 and GLUT3), and enhancing glycolysis [ 107 ]. The metabolic health of the gut can be relayed to the brain via neural and circulatory pathways.…”

Correction to: Shen-Zhi-Ling oral liquid ameliorates cerebral glucose metabolism disorder in early AD via insulin signal transduction pathway in vivo and in vitro

“…Following publication of the original article [ 1 ], the authors identified an error in the column DAPI of Fig. 11 (A1).…”