Jiaotaiwan improves lipid metabolism abnormalities in a mouse model of Alzheimer disease by regulating the AMPK signaling pathway

doi:10.12122/j.issn.1673-4254.2026.10.19

Abstract

Abstract:

Objective To explore whether Jiaotaiwan ameliorates Alzheimer disease (AD) by regulating lipid metabolism via the AMPK pathway. Methods Twenty 3-month-old male transgenic APP/PS1 mice were randomized equally into two groups for treatment with Jiaotaiwan or normal saline via gavage for 4 weeks, with 10 saline-treated wild-type C57BL/6J mice as the control group. Brain lipid deposition, plasma and brain TC, TG and NEFA levels, and expressions of BACE1, Aβ, p-Tau, ZO-1, occludin, AMPK/p-AMPK, SREBP1, ACC, ATGL, and APOE in the brain tissues were detected. In the in vitro experiment, PC12 cell co-cultured with mature adipocytes were treated with Jiaotaiwan, AICAR, or both, and the intracellular lipid droplets, TG, NEFA, AMPK activity, and ACC expression were measured. Results In the AD mouse models, Jiaotaiwan significantly reduced brain lipid deposits, lowered plasma TC and TG levels, increased plasma NEFA level, and decreased brain TG and NEFA expressions without affecting TC expression. Jiaotaiwan treatment also significantly lowered the expressions of cerebral Aβ and p-Tau, increased cerebral occludin expression and p-AMPK/AMPK ratio, and reduced ACC, SREBP1 and APOE expressions without affecting ATGL expression in the mouse models. In the co-cultured cells, Jiaotaiwan obviously alleviated cellular lipid accumulation, lowered cellular TG and NEFA levels, reduced supernatant TG content, and enhanced NEFA release. In both the AD mouse model and co-cultured cell model, Jiaotaiwan significantly lowered Aβ level, increased AMPK activity and p-AMPK/AMPK expression, and lowered the expressions of ACC. Jiaotaiwan combined with AICAR produced a synergistic effect for enhancing p-AMPK/AMPK expressions in the co-cultured cells. Conclusion In the APP/PS1 mouse model of AD, Jiaotaiwan alleviates AD-related lipid deposition and dysregulation by activating AMPK and modulating the downstream lipogenic effectors, providing also protective effects on the blood-brain barrier and neural cells.

Key words: Alzheimer disease, Jiaotaiwan, lipid metabolism, AMPK signaling pathway

Yuqing RUAN, Can CUI, Jingzhe LI, Yan WANG, Xiu WANG. Jiaotaiwan improves lipid metabolism abnormalities in a mouse model of Alzheimer disease by regulating the AMPK signaling pathway[J]. Journal of Southern Medical University, 2026, 46(10): 2509-2517.

Figures/Tables 7

Fig.1 Effect of Jiaotaiwan on Aβ protein and blood-brain barrier in APP/PS1 mice. *P<0.05, **P<0.01 vs APP/PS1 group.

Fig.2 Effect of Jiaotaiwan on lipid metabolism in APP/PS1 double transgenic mice. *P<0.05, **P<0.01 vs APP/PS1 group. TC: Total cholesterol; TG: Triglyceride; NEFA: Non-esterified fatty acid.

Fig.3 Oil Red O staining of the brain tissues of the mice (Upper panel: original magnification： ×20; lower panel: ×200).

Fig.4 Effect of Jiaotaiwan on brain lipids in AD mouse models. *P<0.05, **P<0.01 vs APP/PS1 group.

Fig.5 Effect of Jiaotaiwan on lipid deposition in AD mouse models (Scale bar=200 μm).

Fig.6 Effects of Jiaotaiwan on intracellular and extracellular lipid metabolic products in PC12 cell model of AD. A: Intracellular TG and NEFA content. B: TG and NEFA content in the culture supernatant. *P<0.05, **P<0.01 vs Aβ25-35 group.

Fig.7 Effect of Jiaotaiwan on the AMPK/ACC pathway. A: Effect of Jiaotaiwan on the AMPK pathway in APP/PS1 double transgenic mice. B: Effects of Jiaotaiwan on the AMPK/ACC pathway in AD model cells. C: Effect of Jiaotaiwan on AMPK activity in AD model cells (Scale bar=25 μm). D: Effect of Jiaotaiwan-medicated serum combined with the AMPK agonist on AD model cells. *P<0.05, **P<0.01 vs Aβ25-35 group.

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