Protective Effects of Cannabidiol on Chemotherapy-Induced Oral Mucositis via the Nrf2/Keap1/ARE Signaling Pathways

Figure 9

Protective effects of CBD against chemotherapy-induced OM. 5-FU, used in mice and HOK, triggered injury to basal layer epithelial cells and then induced OM. The pathologies of OM initiate from increased ROS levels, followed by an overburdened inflammatory response and cell apoptosis, resulting in the development of OM. CBD intervention reduces intracellular ROS overproduction, decreases excess inflammatory cytokine secretion, inhibits cell apoptosis, and promotes cell migration. Moreover, CBD treatment increases Nrf2 expression and promotes the translocation of Nrf2 from the cytoplasm to the nucleus, subsequently activating the Nrf2/Keap1/ARE pathways and upregulating the expression levels of downstream antioxidant enzymes to defend epithelial cells from 5-FU damage. Eventually, CBD administration promotes cell regeneration and alleviates OM.