Journal of affective disorders · 2025
Hyperforin-induced gut microbiota metabolite carbocysteine protects against depressive-like behaviors in mice by modulating the colonic mucus barrier.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Zhang Zheng, Xing Bo, Liu Xuhui, Shi Kaixuan, Chen Qingjie
Аннотация
OBJECTIVE: Depression affects millions, and current treatments have limitations, necessitating new approaches. Earlier research confirms Hyperforin's ability to reduce anhedonic behaviors in mice and modulate gut microbiota. This study aims to identify specific metabolic changes induced by Hyperforin that could illuminate its impact on gut microbiome metabolism, possibly uncovering novel metabolites for developing antidepressant therapies.
METHODS: Following the chronic stress model, untargeted metabolomic analysis of fecal samples was conducted to identify metabolic changes induced by Hyperforin. Bioinformatics tools analyzed the origins of differentially expressed metabolites and their correlation with Akkermansia muciniphila and Muribaculum intestinale. The significant metabolite Carbocysteine was further investigated for its antidepressant effects using behavioral assays in a mouse model of depression. Additionally, the response of the colonic mucus barrier was evaluated using Periodic Acid-Schiff (PAS) staining, scanning electron microscopy (SEM), and enzyme-linked immunosorbent assays (ELISA).
RESULTS: Hyperforin significantly altered fecal metabolite profiles in stressed mice, with a notable shift in 239 metabolites mainly associated with co-metabolism pathways and microbiota-specific processes. Among these, Carbocysteine emerged as a key metabolite linked to beneficial bacteria Akkermansia muciniphila and Muribaculum intestinale, with its levels significantly elevated following Hyperforin treatment. Behavioral assessments indicated that Carbocysteine supplementation ameliorated depressive-like behaviors in the chronic restraint stress mouse model. It also enhanced colonic mucus production and integrity.
CONCLUSION: Our research highlights Hyperforin's role in modulating gut microbiota metabolism and identifies Carbocysteine as a potential antidepressant. These findings advance our understanding of the gut-brain axis (GBA) in depression and pave the way for developing new therapeutics.
METHODS: Following the chronic stress model, untargeted metabolomic analysis of fecal samples was conducted to identify metabolic changes induced by Hyperforin. Bioinformatics tools analyzed the origins of differentially expressed metabolites and their correlation with Akkermansia muciniphila and Muribaculum intestinale. The significant metabolite Carbocysteine was further investigated for its antidepressant effects using behavioral assays in a mouse model of depression. Additionally, the response of the colonic mucus barrier was evaluated using Periodic Acid-Schiff (PAS) staining, scanning electron microscopy (SEM), and enzyme-linked immunosorbent assays (ELISA).
RESULTS: Hyperforin significantly altered fecal metabolite profiles in stressed mice, with a notable shift in 239 metabolites mainly associated with co-metabolism pathways and microbiota-specific processes. Among these, Carbocysteine emerged as a key metabolite linked to beneficial bacteria Akkermansia muciniphila and Muribaculum intestinale, with its levels significantly elevated following Hyperforin treatment. Behavioral assessments indicated that Carbocysteine supplementation ameliorated depressive-like behaviors in the chronic restraint stress mouse model. It also enhanced colonic mucus production and integrity.
CONCLUSION: Our research highlights Hyperforin's role in modulating gut microbiota metabolism and identifies Carbocysteine as a potential antidepressant. These findings advance our understanding of the gut-brain axis (GBA) in depression and pave the way for developing new therapeutics.