The therapeutic potential of terpenes in periodontal disease: a systematic review of pre-clinical animal studies.

Periodontal disease is a chronic inflammatory condition affecting the supporting structures of the teeth, and has two main stages: gingivitis and periodontitis. Effective treatment for periodontal disease hinges on resolving inflammation, which can be challenging, patient-dependent. Recently, terpenes and their derivatives have emerged as promising alternatives for managing periodontal disease and its associated tissue complications. This review aims to collect preclinical studies and their recent advances in the biological effects and molecular mechanisms of terpenes in the context of periodontal disease. We performed a systematic and comprehensive search in PubMed, Scopus, Embase. A total of 13 non-clinical studies were included in this review. Information on the types of terpenes, the animals used, the dose and route of administration, the periodontal disease induction model, the samples collected and the observed outcomes. The prevalence of this compound was primarily observed in the regulation of inflammation, achieved through the attenuation of NF-κB, MAPK, and COX-related pathways. Additionally, its role in oxidative control was evidenced by the presence of the hydroxyl (-OH) group in the aromatic ring. Furthermore, the RANKL/RANK/OPG system was modulated by terpenes, which also induced sublethal damage to the cells of periodontopathogenic bacteria. Given their potential, terpenes are emerging as valuable compounds for treating periodontal disease and developing natural product-based medications. Nonetheless, improving the methodological quality of preclinical studies, especially in areas such as blinding and sample size determination, is essential to consolidate new findings.