The Immunomodulatory Effects of Porcupine Bezoar on Cyclophosphamide-Induced Immunosuppression in Rats.

Background/Objectives: Immunosuppression is a serious side effect of chemotherapeutic agents such as cyclophosphamide (CTX) and significantly increases the risk of infection in patients. Porcupine (Hystrix brachyura) bezoar (PB), a traditional medicine derived from the Hystrix brachyura species of porcupine, is renowned for its antioxidant and anti-inflammatory properties. However, its immunomodulatory potential has not been adequately investigated. This study aimed to systematically evaluate the protective effects of PB against CTX-induced immunosuppression and the underlying mechanisms in a rat model. Methods: An immunosuppression model was established in rats through the injection of CTX. The effects of PB on immune function were evaluated through the measurement of serum immunoglobulin (IgA and IgG) and pro-inflammatory cytokine (IL-6 and TNF-α) levels, as well as through a histopathological examination of immune organs. The mechanisms were further elucidated by analysing changes in serum metabolites and gut microbiota composition using integrated metabolomics and 16S rRNA sequencing. Results: Treatment with PB significantly alleviated CTX-induced immunosuppression, as demonstrated by elevated serum levels of IgA and IgG and reduced concentrations of IL-6 and TNF-α. PB also improved the architecture of spleen and thymus tissues. Metabolomic analysis revealed that PB regulated glycerophospholipid metabolism and steroid hormone biosynthesis, thereby reducing pro-inflammatory metabolites such as prostaglandin F2α. Furthermore, PB modulated the gut microbiota, increasing the abundance of beneficial bacteria (e.g., Bacteroidota and Lachnospiraceae) and decreasing that of harmful bacteria (e.g., Romboutsia and Clostridium sensu stricto). Conclusions: This study demonstrates that PB can effectively counteract CTX-induced immunosuppression in rats. This immunomodulatory effect is linked to changes in the gut microbiota and the regulation of specific metabolic pathways. These findings provide a scientific basis for the potential use of PB as an immunoadjuvant therapy, offering new insights into the mechanisms of traditional medicines.