Angelica Sinensis polysaccharide antagonizes 5-Fluorouracil-induced spleen injury and dysfunction by suppressing oxidative stress and apoptosis

Angelica Sinensis polysaccharide (ASP), the main active component of Angelica sinensis, possesses antioxidative and anti-apoptotic properties. In this study, we have investigated the antagonistic effect of ASP on 5-FU-induced injury of mouse spleen in vivo and splenocytes in vitro, and its possible mechanism. Our results showed that ASP inhibited 5-FU-induced decreases in spleen weight and organ index in mice, restored the number of peripheral blood leukocytes and lymphocytes, repaired spleen structure disorder and functional impairment, rescued serum IL-2, IL-6, and IFN-gamma levels, and relieved 5-FU-induced mitochondrial swelling, reduced the oxidant accumu-lation including MDA and ROS, whereas increasing the activities of GSH, SOD and CAT. The mechanism may be related to ASP downregulation of Keap1 protein expression thus motivating the nuclear translocation of Nrf2. Furthermore, ASP alleviated the apoptosis of spleens in vivo and splenocytes in vitro, and reactivated PI3K / AKT signalling. In conclusion, the protective effect of ASP on spleens and splenocytes may be related to the reduction of oxidative stress and apoptosis via reactivation of Nrf2 and PI3K/AKT pathways. This study has provided a new protective agent for minimizing the spleen injury caused by 5-FU and a new idea for improving the prognosis of chemotherapy patients.

Automated summary

In this study, researchers found that Angelica Sinensis polysaccharide (ASP) can antagonize the 5-FU-induced injury of mouse spleen and splenocytes, and the underlying mechanism involves the reduction of oxidative stress and apoptosis by activating Nrf2 and PI3K/AKT pathways. The results showed that ASP can restore the spleen weight and function, improve leukocyte and lymphocyte numbers, and regulate cytokine levels, mitochondria swelling, and oxidant accumulation. ASP also downregulated Keap1 expression and promoted the translocation of Nrf2, while activating the PI3K/AKT signaling pathway. This study provides a new protective agent and approach for minimizing spleen injury and improving the prognosis of chemotherapy patients.