Honokiol Mitigates Ionizing Radiation-Induced Injury by Maintaining the Redox Balance of the TrxR/Trx System

Ionizing radiation like X-rays or heavy ions can induce cellular oxidative stress and damage due to the production of reactive oxygen species. The TrxR/Trx system has a considerable impact on maintaining body redox homeostasis and against cell oxidative damage. In this paper, we described the potential of one natural small molecule, Honokiol (HKL), to repair radiation damage in vivo and in vitro. Pretreatment with HKL significantly protected cell viability and decreased cellular damage, as confirmed by the results of MTT assay, colony formation assay, micronucleus test, and γ-H2AX immunofluorescence analysis. Western blot experiments showed that HKL could mediate the oxidative imbalance of the TrxR/Trx system induced by ionizing radiation. The protective effect of HKL might be associated with regulating the TrxR/Trx system, evidenced by silencing TrxR expression with shRNA. Additional co-culture assays provided evidence that the HKL-precondition might attenuate the ionizing radiation-induced bystander effect. In vivo, studies showed that HKL would improve action against the lung cell tissue of the irradiated mice and prolong mouse survival. The findings indicated that HKL is a potential radioprotective agent that preserves the redox homeostasis of the TrxR/Trx system. Overall, the findings presented here demonstrate that HKL has the potential to be a novel radioprotector capable of cellular protection against radiation-induced injuries. These discoveries hold critical significance for both cancer radiotherapeutics and space radiation protection protocols.