2. Academic Validation
  3. Pedunculoside alleviates cognitive deficits and neuronal cell apoptosis by activating the AMPK signaling cascade

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

  • Chin Med. 2024 Nov 22;19(1):163. doi: 10.1186/s13020-024-01033-6.
Liwei Li # 1,  Jinfeng Sun # 1 2,  Fan Chen # 1,  Li Xiong 1,  Lingyu She 2,  Tang Hao 1,  Yuqing Zeng 1,  Luyao Li 3,  Wei Wang 4,  Xia Zhao 5 6,  Guang Liang 7 8 9
Affiliations

Affiliations

  • 1 Zhejiang TCM Key Laboratory of Pharmacology and Translational Research of Natural Products, School of Pharmaceutical Sciences, Hangzhou Medical College, Hangzhou, 310014, Zhejiang, China.
  • 2 Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, Yanbian University, Yanji, Jilin, 133002, People's Republic of China.
  • 3 School of Pharmaceutical Sciences, Wenzhou Medical University, 1210 University Town, Wenzhou, 325035, Zhejiang, China.
  • 4 Affiliated Yongkang First People's Hospital, Hangzhou Medical College, Yongkang, 321399, Zhejiang, China.
  • 5 Zhejiang TCM Key Laboratory of Pharmacology and Translational Research of Natural Products, School of Pharmaceutical Sciences, Hangzhou Medical College, Hangzhou, 310014, Zhejiang, China. xiazhao@hmc.edu.cn.
  • 6 School of Pharmacy, Hangzhou Medical College, Hangzhou, 311399, Zhejiang, China. xiazhao@hmc.edu.cn.
  • 7 Zhejiang TCM Key Laboratory of Pharmacology and Translational Research of Natural Products, School of Pharmaceutical Sciences, Hangzhou Medical College, Hangzhou, 310014, Zhejiang, China. wzmcliangguang@163.com.
  • 8 Department of Pharmacy and Institute of Inflammation, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, 310014, Zhejiang, China. wzmcliangguang@163.com.
  • 9 School of Pharmacy, Hangzhou Medical College, Hangzhou, 311399, Zhejiang, China. wzmcliangguang@163.com.
  • # Contributed equally.
PMID: 39574131 DOI: 10.1186/s13020-024-01033-6
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.

Keywords

3 × Tg-AD mice; Alzheimer’s disease; Apoptosis; Oxidative stress; Pedunculoside.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z