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Chinese Medicine

Chinese Medicine

IF: 5.3
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Pedunculoside alleviates cognitive deficits and neuronal cell apoptosis by activating the AMPK signaling cascade

Published:22 November 2024 DOI: 10.1186/s13020-024-01033-6 PMID: 39574131
Li, Liwei, Sun, Jinfeng, Chen, Fan, Xiong, Li, She, Lingyu, Hao, Tang, Zeng, Yuqing, Li, Luyao, Wang, Wei, Zhao, Xia, Liang, Guang

Abstract

Background: Mitochondrial dysfunction emerges as an early pathological hallmark of Alzheimer's disease (AD). The reduction in mitochondrial membrane potential and the elevation of reactive oxygen species (ROS) production are pivotal in the initiation of neuronal cell apoptosis. Pedunculoside(Ped), a novel triterpene saponin derived from the dried barks of Ilex rotunda Thunb, exhibits a potent anti-inflammatory effect. In the course of drug screening, we discovered that Ped offers significant protection against apoptosis induced by Aβ1-42. Nevertheless, the role and mechanism of Ped in AD are yet to be elucidated.

Methods: Oxidative stress was evaluated by measuring mitochondrial membrane potential and intracellular ROS production. The expression of proteins associated with apoptosis was determined using western blot analysis and flow cytometry. In vivo, the pathological characteristics of AD were investigated through Western blot and tissue immunofluorescence techniques. Cognitive function was assessed using the Morris Water Maze and Novel Object Recognition tests.

Results: We demonstrated that Ped decreased apoptosis in PC12 cells, reduced the generation of intracellular ROS, and restored mitochondrial membrane potential. Mechanistically, we found that the protective effect of Ped against Aβ-induced neurotoxicity was associated with activation of the AMPK/GSK-3β/Nrf2 signaling pathway. In vivo, Ped alleviated memory deficits and inhibited neuronal apoptosis, inflammation, and oxidative stress in the hippocampus of 3?×?Tg AD mice, along with the activation of the AMPK signaling pathway.

Conclusion: The findings indicate that Ped exerts its neuroprotective effects against oxidative stress and apoptosis through the AMPK signaling cascade. The results demonstrate that Ped is a potential candidate for the treatment of AD.

Substances (6)

Materials
Procduct Name CAS Molecular Formula Supplier Price
Dimethyl sulfoxide 67-68-5 C2H6OS 1925 suppliers $5.00-$120900.00
Bovine albumin 9048-46-8 N/A 915 suppliers $15.00-$18680.00
Triton X-100 9002-93-1 (C2H4O)nC14H22O 846 suppliers $16.00-$5950.00
Trypsin 9002-07-7 C35H47N7O10 739 suppliers $19.90-$73956.00
Donepezil 120014-06-4 C24H29NO3 396 suppliers $5.00-$2674.98
pedunculoside 42719-32-4 C36H58O10 197 suppliers Inquiry

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