Correlations Between Amelioration of Rotenone-Induced Parkinson’s Symptoms by Amomum tsaoko Flavonoids and Gut Microbiota in Mice

Parkinson's disease (PD) is the second most common neurodegenerative disease, but the existing therapeutic drugs for PD have limitations; thus, there is an urgent need to discover new methods of prevention and treatment. <i>Amomum tsaoko</i> Crevost et Lemarie (AT) is a classic traditional Chinese medicine and food. Its main pharmacological effect is the regulation of the gastrointestinal tract. To date, no studies on the use of AT or its extracts to treat PD have been reported. In this study, a rotenone-induced PD mouse model was utilized to evaluate the protective effect of <i>Amomum tsaoko</i> flavonoids (ATFs) and to elucidate the role of the gut microbiota in this effect. The results demonstrated that ATFs not only ameliorated the motor and constipation symptoms but also reduced the loss of nigrostriatal dopaminergic neurons. Furthermore, ATFs reduced the expression of inflammation-related genes (<i>TNF-α</i>, <i>IL-1β</i>, <i>IL-6</i>, <i>COX-2</i>, and <i>MCP-1</i>) and increased the expression of gut barrier-related genes (<i>Muc-2</i>, <i>ZO-1</i>, <i>Occludin</i>, <i>Claudin3</i>, and <i>Claudin4</i>) in the colon. Notably, ATFs were able to reverse rotenone-induced gut dysbiosis, including a significant decrease in the abundance of conditionally pathogenic bacteria (<i>Desulfovibrio</i>, <i>Provotellaceae UCG-001</i>, the <i>Lachnospiraceae</i>_<i>NK4A136_group</i>, <i>norank_f_Erysipelotrichacea</i>, and the <i>Eubacterium nodatum group</i>) and an increase in the abundance of probiotics (<i>Bifidobacterium</i> and <i>Faecalibaculum</i>). Interestingly, these genera were found to be significantly associated with PD motor symptoms and constipation indicators. This suggests that ATFs have the potential to alleviate PD symptoms through the modulation of gut microbes. These findings provide a solid foundation for further investigations into the anti-PD mechanism of ATFs and their potential in the prevention and treatment of PD.