2. Academic Validation
  3. QBT improved cognitive dysfunction in rats with vascular dementia by regulating the Nrf2/xCT/GPX4 and NLRP3/Caspase-1/GSDMD pathways to inhibit ferroptosis and pyroptosis of neurons

QBT improved cognitive dysfunction in rats with vascular dementia by regulating the Nrf2/xCT/GPX4 and NLRP3/Caspase-1/GSDMD pathways to inhibit ferroptosis and pyroptosis of neurons

  • Int Immunopharmacol. 2024 Dec 5;142(Pt A):113070. doi: 10.1016/j.intimp.2024.113070.
Lu Feng 1,  Yi-Jin Wu 1,  Yan-Rong Yang 1,  Bing-Jie Yue 1,  Cheng Peng 2,  Chu Chen 3,  Fu Peng 1,  Jun-Rong Du 4,  Fang-Yi Long 5
Affiliations

Affiliations

  • 1 Department of Pharmacology, Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan, China.
  • 2 State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu, Sichuan, China. Electronic address: pengchengchengdu@126.com.
  • 3 Laboratory of Quality and Innovation Research of Chinese Materia Medica, Sichuan Academy of Chinese Medicine, Chengdu, Sichuan, China.
  • 4 Department of Pharmacology, Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan, China. Electronic address: dujunrong@scu.edu.cn.
  • 5 Laboratory Medicine Center, Sichuan Provincial Maternity and Child Health Care Hospital, Chengdu, Sichuan, China. Electronic address: longfangyi1986@sina.com.
PMID: 39265351 DOI: 10.1016/j.intimp.2024.113070
Abstract

Background: The novel phthalein component QBT, extracted from Ligusticum chuanxiong, shows promising biological activity against cerebrovascular diseases. This study focused on Ferroptosis and Pyroptosis to explore the effects of QBT on nerve injury, cognitive dysfunction, and related mechanisms in a rat model of vascular dementia (VaD).

Methods: We established a rat model of VaD and administered QBT as a treatment. Cognitive dysfunction in VaD rats was evaluated using novel object recognition and Morris water maze tests. Neuronal damage and loss in the brain tissues of VaD rats were assessed with Nissl staining and immunofluorescence. Furthermore, we investigated the neuroprotective mechanisms of QBT by modulating the nuclear factor erythroid 2-related factor 2 (Nrf2)/cystine-glutamate antiporter (xCT)/Glutathione Peroxidase 4 (GPX4) and NOD-like Receptor family pyrin domain-containing 3 (NLRP3)/cysteine-requiring aspartate protease-1 (Caspase-1)/Gasdermin D (GSDMD) pathways to inhibit Ferroptosis and Pyroptosis both in vivo and in vitro.

Results: Our findings indicated that QBT significantly ameliorated neuronal damage and cognitive dysfunction in VaD rats. Additionally, QBT reversed abnormal changes associated with Ferroptosis and Pyroptosis in the brains of VaD rats, concurrently up-regulating the Nrf2/xCT/GPX4 pathway and down-regulating the NLRP3/Caspase-1/GSDMD pathway to inhibit Ferroptosis and Pyroptosis in neuronal cells, thereby exerting a neuroprotective role.

Conclusion: In summary, QBT effectively mitigated neuronal damage and cognitive dysfunction in VaD rats, demonstrating a neuroprotective effect by inhibiting Ferroptosis and Pyroptosis in neuronal cells. This study offers a novel perspective and theoretical foundation for the future development of drugs targeting VaD.

Keywords

Cognitive dysfunction; Ferroptosis; Pyroptosis; QBT; Vascular dementia.

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