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

• Published in: Journal of ethnopharmacology 2023-02, Vol.302, p.115872, Article 115872
• Main Authors: Huang, Huai-Syuan, Lin, Yu-En, Panyod, Suraphan, Chen, Rou-An, Lin, Ying-Cheng, Chai, Laura Min Xuan, Hsu, Cheng-Chih, Wu, Wei-Kai, Lu, Kuan-Hung, Huang, Yun-Ju, Sheen, Lee-Yan
• Format: Article
• Language: English
• Subjects: Cognitive impairment; Depression; Gastrodia elata Blume water extract; Gut microbiome; Unpredictable chronic mild stress model
• ISSN: 0378-8741; 1872-7573
• DOI: 10.1016/j.jep.2022.115872

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. 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. 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. 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). 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. [Display omitted] •Gastrodia elata Blume water extract (WGE) restored sucrose preference, exploratory behavior, and recognition ability of ApoE−/− mice in the behavior test.•WGE decreased the levels of serum corticosterone and Aβ-42 in ApoE−/− mice.•WGE reduced the 5-HT and DA turnover rates in the prefrontal cortex.•WGE ele