Berberine Improves Depression‐Like Behaviors and Gastrointestinal Dysfunction in 6‐Hydroxydopamine‐Induced Parkinson's Disease Rats

ABSTRACT Background Berberine (BBR) enhances the production of levodopa in gut microbes, which is converted to dopamine in the brain of Parkinson's disease (PD). However, limited research has explored the effects of BBR on non‐motor symptoms, such as depression and gastrointestinal (GI) dysfunction in PD. Methods 6‐hydroxydopamine‐induced (6‐OHDA) PD rats were utilized in this study, and depression‐like behaviors were detected via the sucrose preference test and open field test. Key Results The 6‐OHDA rats exhibited depression‐like behaviors, delayed GI transit, decreased colonic motility, and increased mucosal permeability. BBR gavage effectively improved depression‐like behaviors, increased dopamine and 5‐HT content in the midbrain and orexin A (OXA) content in the hypothalamus, but decreased corticotropin‐releasing factor (CRF) content in the hypothalamus of 6‐OHDA rats. Moreover, BBR treatment shortened whole GI transit time, enhanced distal colonic motility, and restored colonic mucosal permeability in 6‐OHDA rats. Furthermore, expression of neuronal nitric oxide synthase protein, choline acetyltransferase mRNA levels, intensity of glial fibrillary acidic protein‐positive enteric glial cells (EGCs), glial cell‐derived neurotrophic factor protein, and goblet cell numbers were increased in the distal colon of 6‐OHDA rats after BBR treatment. Conclusions and Inferences These findings suggested that BBR ameliorated the colonic dysfunction in 6‐OHDA rats and modulated changes in enteric neurotransmitters and EGCs. Moreover, BBR regulated monoamines in the midbrain and OXA and CRF in the hypothalamus, which are associated with depression‐like behaviors in 6‐OHDA rats. This study provides a theoretical and experimental foundation for the potential application of BBR in treating non‐motor symptoms of PD.