Anti-depressive-like and cognitive impairment alleviation effects of Gastrodia elata Blume water extract is related to gut microbiome remodeling in ApoE mice exposed to unpredictable chronic mild stress.

Ethnopharmacology Relevance: Gastrodia elata Blume (GE) is a traditional Chinese dietary therapy used to treat neurological disorders. Gastrodia elata Blume water extract (WGE) has been shown to ameliorate inflammation and improve social frustration in mice in a chronic social defeat model. However, studies on the anti-depressive-like effects and cognitive impairment alleviation related to the impact of WGE on the gut microbiome of ApoE mice remain elusive.

Aim Of The Study: The present study aimed to investigate the anti-depressive-like effect and cognitive impairment alleviation and mechanisms of WGE in ApoE mice subjected to unpredictable chronic mild stress (UCMS), as well as its impact on the gut microbiome of the mice.

Materials And Methods: Sixty ApoE mice (6 months old) were randomly grouped into six groups: control, UCMS, WGE groups [5, 10, 20 mL WGE/kg body weight (bw) + UCMS], and a positive group (fluoxetine 20 mg/kg bw + UCMS). After four weeks of the UCMS paradigm, the sucrose preference, novel object recognition, and open field tests were conducted. The neurotransmitters serotonin (5-HT), dopamine (DA) and their metabolites were measured in the prefrontal cortex. Serum was collected to measure corticosterone and amyloid-42 (Aβ-42) levels. Feces were collected, and the gut microbiome was analyzed.

Results: WGE restored sucrose preference, exploratory behavior, recognition ability, and decreased the levels of serum corticosterone and Aβ-42 in ApoE mice to alleviate depressive-like behavior and cognitive impairment. Furthermore, WGE regulated the monoamine neurotransmitter via reduced the 5-HT and DA turnover rates in the prefrontal cortex. Moreover, WGE elevated the levels of potentially beneficial bacteria such as Bifidobacterium, Akkermansia, Alloprevotella, Defluviitaleaceae_UCG-011, and Bifidobacterium pseudolongum as well as balanced fecal short-chain fatty acids (SCFAs).

Conclusion: WGE demonstrates anti-depressive-like effects, cognitive impairment alleviation, and gut microbiome and metabolite regulation in ApoE mice. Our results support the possibility of developing a functional and complementary medicine to prevent or alleviate depression and cognitive decline using WGE in CVDs patients.