The Anti-Inflammatory Effects of Phyto Cannabinoids on IL-1β-induced PGE2 Production in Gingival Fibroblasts

Objectives: Periodontal disease (PD), which is commonly associated with inflammatory pain, can eventually lead to tooth and bone loss.Nonsteroid anti-inflammatory drugs (NSAIDs) are commonly prescribed to manage acute inflammatory pain by inhibiting prostaglandin production.The endocannabinoid system (ECS), such as anandamide (AEA), 2-arachidonoyl glycerol (2-AG) and phytocannabinoides (pCBs) also plays a role in the modulation of prostaglandins and inflammation.This study aims to build on a previous publication by identifying the dosedependent response of non-psychotropic phytocannabinoids (pCBs) on prostaglandin E2 (PGE2) levels in primary human gingival fibroblasts (HGFs) stimulated with interleukin-1β (IL-1β).The study hypothesizes that the pharmacological properties of phytocannabinoids (pCBs) are dose-dependent and may produce different outcomes on prostaglandin activity.Methods: HGFs were cultured and the conditioned media was treated with IL-1β (1ng/ml) and varying doses of cannabidivarin (CBVN or CBDV, dose), cannabigerol (CBG), and cannabidiol (CBD) or a nonselective cox inhibitor, Indomethacin (10µM) on HGFs.At the end of the treatment PEG2 was determined using The CisBio HTRF PGE2 assay kit Results: CBVN, CBG, and CBD all showed significant suppression of IL-1β stimulated PGE2 in HGFs at a lower concentration.CBG significantly suppressed PGE2 levels at 0.3-1.0µg/ml.CBD exhibited suppression of PGE2 at 0.1-0.75µg/ml, while significantly increasing PGE2 levels at 1.0-5.0µg/ml.CBVN exhibited the most profound suppression of PGE2 at 0.1-1.0µg/ml, but significantly elevated PGE2 at 2.0-5.0 µg/ml.The treatment with indomethacin (10µM) resulted in suppression of PGE2 significantly back to control levels. Conclusion:The crosstalk between prostaglandins and the ECS in the modulation of inflammation provides a potential therapeutic option for the management of inflammatory pain.However, it is important to understand the limitations of each pCBs, as at lower doses pCBs reduce PGE2 levels, while showing increased PGE2 at higher doses promoting inflammatory effects.The pCBs alone or in combination may benefit the development of new therapeutic strategies for pain management during periodontal therapy aiding in improving public oral health.