Protective effect of Angelica sinensis polysaccharide on chemotherapy-injured POI rats and its impact on intestinal flora

Maoyuan Wu¹Haixia Shu¹Min Wang¹Yan Xu¹Yunhan Zhang¹Xiaoling Jiang²Lixia Zhang¹Xuemei Chen¹Lianli He^1*

• ¹遵义医科大学第三附属医院, 贵州遵义, China
• ²第三附属医院, Zunyi Medical University, Zunyi, China

Objective This study aimed to investigate the therapeutic effects and mechanisms of Angelica sinensis polysaccharide (ASP) on a chemotherapy-induced premature ovarian insufficiency (POI) rat model and to screen for the optimal therapeutic dose. Methods SD female rats were used to establish a POI rat model by intraperitoneal injection of cyclophosphamide (CTX) + busulfan. POI rats were treated with ASP at doses of 80, 160, and 320 mg/kg/day for 21 days. Ovarian histomorphology and follicular development were examined by H&E staining. Serum levels of FSH, LH, E₂, AMH, and inflammatory cytokines (IL-6, IL-1β, TNF-α) were measured. Ovarian oxidative stress was assessed via MDA, SOD, GSH-Px, and ROS levels. Gut microbiota composition was analyzed by 16S rDNA sequencing, and Spearman correlation analysis was used to evaluate associations between differential microbiota and ovarian indicators. Results ASP treatment improved sex hormone secretion in chemotherapy-induced POI rats, increased E2 and AMH levels, decreased FSH and LH levels, improved ovarian tissue structure, and increased follicle growth at all stages. ASP treatment also improved serum inflammatory levels in POI rats, reducing IL-6, IL-1β, and TNF-α levels; it decreased oxidative stress levels in ovarian tissue, inhibited ROS and MDA activity, and increased SOD and GSH-Px activity. Gut microbiota differential analysis: Chemotherapy-induced POI rats exhibit gut microbiota dysbiosis. After ASP treatment, αand βdiversity of the gut microbiota changed, increasing the relative abundance of beneficial bacteria and decreasing the relative abundance of harmful bacteria; Spearman correlation analysis was performed between the main differential microbiota and serum sex hormone levels, pro-inflammatory cytokine levels, and ovarian tissue oxidative stress levels. The results showed that some beneficial bacteria were positively correlated with E2, AMH, SOD, and GSH-Px levels, and negatively correlated with FSH, LH, MDA, IL-6, IL-1β, and TNF-α levels. Conclusion ASP ameliorates chemotherapy-induced POI in rats by improving serum hormone levels, promoting follicular development, and suppressing inflammation and oxidative stress, with medium and high doses showing significant efficacy. Furthermore, ASP reshapes the gut microbiota, and the altered microbiota strongly correlate with ovarian function indicators, suggesting that gut microbiota may serve as a new therapeutic approach for POI.