Therapeutic potential of Astragalus membranaceus—Pueraria lobata decoction for the treatment of chemotherapy bowel injury

Abstract Intestinal mucositis (IM) is one of the most serious side effects of the chemotherapeutic agent irinotecan (CPT‐11). Astragalus membranaceus ‐ Pueraria lobata decoction is from the ancient medical book Zhengzhihuibu, has been reported to be used for the treatment of diabetes and hypertension. However, the beneficial effect and mechanism of AP on chemotherapy intestinal mucositis (CIM) remain largely unknown. This study aimed to investigate the efficacy and mechanism of Astragalus membranaceus ‐ Pueraria lobata decoction (AP) in treating CIM. The beneficial effect and mechanism of AP on chemotherapy intestinal mucositis (CIM) were detected using Drosophila model, and combination with RT qPCR, transcriptomics. AP supplementation could significantly alleviate the CPT‐11‐induced body injury in Drosophila , such as increasing the survival rate, recovering the impaired digestion, improving the movement, and repairing the reproduction and developmental processes. Administration of AP remarkably alleviated the IM caused by CPT‐11, including inhibiting the excretion, repairing the intestinal atrophy, improving the acid–base homeostasis imbalance, and inhibiting the disruption of intestinal structure. Mechanistic studies revealed that the protective role of AP against CPT‐11 induced intestinal injury was regulated mainly by inhibiting immune‐related Toll and Imd pathways, and enhancing the antioxidant capacity. Taken together, these results suggest that AP may be a novel agent to relieve CIM.