Dihydromyricetin alleviates hippocampal ferroptosis in type 2 diabetic cognitive impairment rats via inhibiting the JNK-inflammatory factor pathway

Zihan Wang; Shuidong Feng; Qi Li; Zhenjiang Song; Jianqin He; Sisi Yang; Canqun Yan; Hongyan Ling

doi:10.1016/j.neulet.2023.137404

Dihydromyricetin alleviates hippocampal ferroptosis in type 2 diabetic cognitive impairment rats via inhibiting the JNK-inflammatory factor pathway

Neurosci Lett. 2023 Aug 24:812:137404. doi: 10.1016/j.neulet.2023.137404. Epub 2023 Jul 21.

Authors

Zihan Wang¹, Shuidong Feng², Qi Li³, Zhenjiang Song³, Jianqin He³, Sisi Yang³, Canqun Yan⁴, Hongyan Ling⁵

Affiliations

¹ Department of Physiology, Hengyang Medical School, University of South China, Hengyang 421001, Hunan, China; School of Medicine, The Chinese University of Hong Kong, Shenzhen 518172, Guangdong, China.
² Department of Social Medicine and Health Service Management, School of Public Health, University of South China, Hengyang 421001, Hunan, China.
³ Department of Physiology, Hengyang Medical School, University of South China, Hengyang 421001, Hunan, China.
⁴ The Health Management Center, The Second Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang 421001, Hunan, China.
⁵ Department of Physiology, Hengyang Medical School, University of South China, Hengyang 421001, Hunan, China. Electronic address: linghongyan0203@126.com.

PMID: 37482219
DOI: 10.1016/j.neulet.2023.137404

Abstract

Type 2 diabetes mellitus (T2DM) is frequently associated with diabetic cognitive impairment (DCI), and recent studies have shown a strong association between DCI and hippocampal ferroptosis. In this study, we administered dihydromyricetin (DHM) or JNK inhibitor SP600125, to T2DM rats and monitored changes in blood glucose levels, conducted behavioral tests, and detected changes in JNK, inflammatory factors and ferroptosis-related indicators. Our findings demonstrated that T2DM rats displayed signs of cognitive impairment (CI), with ferrozine assays indicating elevated iron content in the hippocampus. Concurrently, there was an increase in p-JNK activity and inflammatory factors IL-6 and TNF-α in the hippocampal region of these rats. Furthermore, we observed elevated levels of Fe²⁺, MDA, ROS, LPO, and ACSL4, along with a decrease in GPX4 and GSH, suggesting the occurrence of hippocampal ferroptosis. SP600125 application reversed these changes in the T2DM rats, although it exhibited no significant effects in the control group. Treatment with high and low doses of DHM led to a reduction in p-JNK expression, inflammatory factor-related proteins, and iron accumulation in the hippocampal region, effectively alleviating hippocampal ferroptosis in T2DM rats. No notable effects of DHM were observed in the control group. To conclude, our study suggests that DHM can potentially alleviate hippocampal ferroptosis of T2DM cognitive impairment rats, primarily by suppressing the JNK-inflammatory factor pathway in the hippocampus.

Keywords: Cognitive impairment; Dihydromyricetin; Ferroptosis; JNK-inflammatory factor pathway; Type 2 diabetes mellitus.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cognitive Dysfunction* / drug therapy
Diabetes Mellitus, Type 2* / complications
Diabetes Mellitus, Type 2* / drug therapy
Ferroptosis*
Hippocampus
Iron
Rats

Substances

pyrazolanthrone
dihydromyricetin
Iron