CBD Promotes Oral Ulcer Healing via Inhibiting CMPK2-Mediated Inflammasome

• Published in: Journal of dental research Vol. 101; no. 2; pp. 206 - 215
• Main Authors: Qi, X., Lin, W., Wu, Y., Li, Q., Zhou, X., Li, H., Xiao, Q., Wang, Y., Shao, B., Yuan, Q.
• Format: Journal Article
• Language: English
• Published: Los Angeles, CA SAGE Publications 01.02.2022; SAGE PUBLICATIONS, INC
• Subjects: Animals; Cannabidiol; Cannabinoid CB1 receptors; Cannabinoids; Inflammasomes; Mice; Mice, Inbred NOD; Mitochondrial DNA; NLR Family, Pyrin Domain-Containing 3 Protein; Oral Ulcer - drug therapy; Pain; Peroxisome proliferator-activated receptors; Pyrin protein; Pyroptosis; Trauma; Ulcers; Uridine; cannabidiol; NLRP3 inflammasomes; CB1; oral ulcers; mitochondria; PPARγ
• ISSN: 0022-0345; 1544-0591
• DOI: 10.1177/00220345211024528

Oral ulcer is a common oral inflammatory lesion accompanied by severe pain but with few effective treatments. Cannabidiol (CBD) is recently emerging for its therapeutic potential in a range of diseases, including inflammatory conditions and cancers. Here we show that CBD oral spray on acid- or trauma-induced oral ulcers on mice tongue inhibits inflammation, relieves pain, and accelerates lesion closure. Notably, the enrichment of genes associated with the NOD, LRR, and NLRP3 pyrin domain–containing protein 3 (NLRP3) inflammasome pathway is downregulated after CBD treatment. The expression of cleaved-gasdermin D (GSDMD) and the percentage of pyroptotic cells are reduced as well. In addition, CBD decreases the expression of cytidine/uridine monophosphate kinase 2 (CMPK2), which subsequently inhibits the generation of oxidized mitochondria DNA and suppresses inflammasome activation. These immunomodulating effects of CBD are mostly blocked by peroxisome proliferator activated receptor γ (PPARγ) antagonist and partially antagonized by CB1 receptor antagonist. Our results demonstrate that CBD accelerates oral ulcer healing by inhibiting CMPK2-mediated NLRP3 inflammasome activation and pyroptosis, which are mediated mostly by PPARγ in the nucleus and partially by CB1 in the plasma membrane.