Lycium barbarum (Wolfberry) glycopeptide prevents stress-induced anxiety disorders by regulating oxidative stress and ferroptosis in the medial prefrontal cortex

Yelin Dai; Junxiu Guo; Borui Zhang; Junlin Chen; Haibin Ou; Rong-Rong He; Kwok-Fai So; Li Zhang

doi:10.1016/j.phymed.2023.154864

Lycium barbarum (Wolfberry) glycopeptide prevents stress-induced anxiety disorders by regulating oxidative stress and ferroptosis in the medial prefrontal cortex

Phytomedicine. 2023 Jul 25:116:154864. doi: 10.1016/j.phymed.2023.154864. Epub 2023 May 9.

Authors

Yelin Dai¹, Junxiu Guo¹, Borui Zhang¹, Junlin Chen¹, Haibin Ou², Rong-Rong He³, Kwok-Fai So⁴, Li Zhang⁵

Affiliations

¹ Key Laboratory of CNS Regeneration (Ministry of Education), Guangdong-Hong Kong-Macau Institute of CNS Regeneration, Jinan University, Guangzhou, China.
² College of Life Science and Technology, Jinan University, Guangzhou, China.
³ Guangdong Engineering Research Center of Chinese Medicine & Disease Susceptibility, Jinan University, Guangzhou, China.
⁴ Key Laboratory of CNS Regeneration (Ministry of Education), Guangdong-Hong Kong-Macau Institute of CNS Regeneration, Jinan University, Guangzhou, China; State Key Laboratory of Brain and Cognitive Science, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China; Neuroscience and Neurorehabilitation Institute, University of Health and Rehabilitation Sciences, Qingdao, China; Center for Exercise and Brain Science, School of Psychology, Shanghai University of Sport, Shanghai, China. Electronic address: hrmaskf@hku.hk.
⁵ Key Laboratory of CNS Regeneration (Ministry of Education), Guangdong-Hong Kong-Macau Institute of CNS Regeneration, Jinan University, Guangzhou, China; Neuroscience and Neurorehabilitation Institute, University of Health and Rehabilitation Sciences, Qingdao, China; Center for Exercise and Brain Science, School of Psychology, Shanghai University of Sport, Shanghai, China. Electronic address: zhangli@jnu.edu.cn.

PMID: 37182278
DOI: 10.1016/j.phymed.2023.154864

Abstract

Background: Lycium barbarum (Wolfberry) extract has been shown to be effective in neuroprotection against aging or neural injury. Knowledge of its potential roles and biological mechanisms in relieving mental disorders, however, remains limited.

Purpose: To investigate the potency of Lycium barbarum glycopeptide (LbGp) in alleviating anxiety disorders and the related biological mechanisms.

Methods: LbGp was administrated to mice subjected to 14 days of chronic restrain stress (CRS) via the intragastric route. The anxiolytic effect was evaluated by a battery of behavioral assays. The morphology of neurons and glial cells was evaluated, and cortical neuronal calcium transients were recorded in vivo. The molecular mechanism of LbGp was also investigated.

Results: LbGp effectively relieved anxiety-like and depressive behaviors under CRS. Mechanistic studies further showed that LbGp treatment relieved oxidative stress and lipid peroxidation in the medial prefrontal cortex (mPFC). In particular, the ferroptosis pathway was inhibited by LbGp, revealing a previously unrecognized mechanism of the anxiolytic role of wolfberry extract.

Conclusion: In summary, our results supported the future development of LbGp to prevent or ameliorate stress-induced anxiety disorders. Our work provides a promising strategy for early intervention for pateitents with mental disorders by applying natural plant extracts.

Keywords: Anxiety disorder; Ferroptosis; Wolfberry extracts.

MeSH terms

Animals
Anxiety
Anxiety Disorders / drug therapy
Ferroptosis*
Glycopeptides / pharmacology
Lycium* / chemistry
Mice
Oxidative Stress
Plant Extracts / pharmacology
Plant Extracts / therapeutic use
Prefrontal Cortex

Substances

Glycopeptides
Plant Extracts