Moringa oleifera Lam. leaf extract safely inhibits periodontitis by regulating the expression of p38α/MAPK14-OPG/RANKL.

Periodontitis is a chronic disease clinically defined by loss of alveolar bone and connective tissue degeneration. Although Moringa oleifera Lam. (MO), a tree belonging to the Moringacea family, is widely used as an anti-inflammatory agent, its effect on periodontitis is still unclear. In this work, the phenol compounds in MO leaf extract (MOL) were identified by UPLC-ESI-MS/MS, and the anti-periodontitis effects and mechanism of MOL were predicted using network pharmacology and molecular docking. Moreover, the cytotoxic, antioxidant, and anti-periodontitis properties of MOL were confirmed in vivo and in vitro. In total, 88 phenolic compounds and 234 potential MOL periodontitis targets were screened, involving 2916 biological processes (BP). The p38α MAPK (MAPK14) pathway and OPG/RANKL complex were predicted to be involved in the process of molecular docking. Furthermore, experimental validation suggested that MOL significantly ameliorated inflammation and reduced alveolar bone resorption. The OPG/RANKL ratio was regulated through the inhibition of MAPK14, and the anti-periodontitis effect was realized by the antioxidant properties of MOL. Hematoxylin and eosin (H&E) staining of rat vital organs and the survival rate of RAW 264.7 cells confirmed the safety of MOL. The present study provides valuable insights into how MOL reduces inflammation and alveolar bone resorption associated with periodontitis. In conclusion, MOL safely inhibits chronic periodontitis highly likely by regulating the expression of p38α/MAPK14-OPG/RANKL. Network pharmacology coupled with experimental validation is an effective way to find new drugs in the future. DATA AVAILABILITY STATEMENT: The original data presented in the study are included in the article. Further inquiries can be directed to the corresponding authors.