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

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