Rutin protects against cyclophosphamide induced immunological stress by inhibiting TLR4-NF-κB-mediated inflammation and activating the Nrf2- mediated antioxidant responses

Abstract

Rutin exists in many plants and has many pharmacological effects, including antioxidant, anti-inflammatory, antibacterial and immune regulation. In this study, the immunomodulatory and antioxidant effects of rutin were revealed by cyclophosphamide (CTX) induced mice model. The expression level of the related genes and proteins was investigated by quantification real-time PCR and Western blotting methods, respectively. The results shown that rutin could significantly improve the damage of spleen and thymus caused by CTX, and very significantly (P<0.01) reduce the increasing content of TNF-α and IL-6. It also could significantly (P<0.01) decrease the relative expression level of TLR4, MyD88, TRAF6, and p65 genes and proteins, and significantly increase (P<0.01) the expression of IκB gene, phosphorylated p65 and IκB proteins. Moreover, rutin could significantly (P<0.01) reduce the MDA content and enhance the SOD activity, and increase the expression levels of Nrf2, HO-1 genes and proteins in the livers. In conclusion, rutin can regulate the secretion of cytokines and protect immune organs by regulation the expression level of the related genes and proteins in the TLR4-MyD88-NF-κB signaling pathway; and it can also play an antioxidative stress role by activation of the Nrf2/HO-1 signaling pathway. This research will lay a certain foundation for the screening of immunomodulators and antioxidants.