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6-Gingerol (6G) is the main phenolic active component of ginger, which has a certain protective effect against liver injury induced by drugs, and chemical pollutants. However, the mechanism of protection of 6G against arsenic trioxide (ATO)-induced liver injury remains unclear. The network pharmacology and animal experiment results respectively indicated that oxidative stress and inflammatory responses were closely related to ATO-induced liver injury. 6G can alleviate ATO-induced liver injury and oxidative stress. Furthermore, 6G can attenuate the release of pro-inflammatory factors induced by ATO and reduce the expressions of NLRP3, ASC, Caspase-1 and gasdermin-D. The results showed that the activation of NLRP3 inflammatory and its induced pyroptosis play critical roles in liver injury caused by ATO. Furthermore, 6G can suppress the ROS-NLRP3 inflammasome signaling pathway, which may be an effective strategy for the treatment of ATO-induced liver injury.

Cardiotoxicity is a serious side effect of arsenic trioxide (ATO) which hinders its clinical use in cancer chemotherapy. Danshensu (DSS) has potential applications in the food and healthcare industry to promote cardiovascular health. The experiment aims to investigate the effects of DSS against ATO-induced cardiotoxicity and its possible mechanism. Our results demonstrated that DSS improved cardiac dysfunction, alleviated histopathological damage, enhanced antioxidant activity, attenuated cardiomyocyte apoptosis and suppressed inflammation. Further studies showed that DSS prevented ATO-caused activation of NF-κB by inhibiting the phosphorylation of AKT and IKK, degradation of IκBα, and nuclear translocation of NF-κB. In H9c2 cardiomyocytes, DSS significantly increased cell survival rate and inhibited ATO-mediated expression of p-AKT, p-IKKα/β, p-IκBα, and NF-κB. Notably, the efficacy of DSS was synergistically increased by AKT inhibitor GSK690693. To sum up, DSS effectively ameliorated ATO-induced cardiac toxicity in vivo and in vitro, which may be achieved through inhibition of the AKT/IKK/NF-κB pathway.