Panaxadiol saponins-loaded gel for periodontitis therapy: anti-inflammatory and microbiota-modulating effects.

Abstract

OBJECTIVE: To evaluate the anti-inflammatory activity and mechanism of Panaxadiol saponins (PDS), develop a PDS-based gel for periodontitis treatment, and evaluate its therapeutic efficacy using a rat model of periodontitis. METHODS: The anti-inflammatory effects of PDS were assessed using LPS-induced RAW264.7 cells. ELISA and RT-qPCR were performed to detect inflammatory factors; Western blotting analyzed MAPK/NF-κB pathway-related proteins. A single-factor experiment was used to examine the effects of the dosages of carbomer 940, propylene glycol, and triethanolamine on the properties of the PDS gel and to evaluate itsrelease versuspermeation and retention on oral mucosa. A rat periodontitis model was established by ligation plus high-sugar feeding, and the efficacy of PDS gel in ameliorating periodontitis in rats was evaluated using gingival index scoring, micro-CT, HE staining, ELISA, and RT-qPCR to assess the state of periodontal tissues and inflammatory responses, and salivary microbiota analysis using 16S rRNA sequencing. RESULTS: PDS significantly reduced NO, IL-6, IL-1β, and TNF-α release, inhibited their mRNA expression, and suppressed MAPK/NF-κB pathway-related proteins in LPS-induced RAW264.7 cells. The PDS gel exhibited good physicochemical properties, release performance, and mucosal permeability. PDS gel decreased gingival index, attenuated alveolar bone loss, reduced inflammatory cell infiltration, and lowered IL-6, IL-1β, TNF-α, and RANKL mRNA levels in serum and periodontal tissue. It also regulated and restored the balance of salivary flora. CONCLUSION: PDS gel can inhibit the MAPK/NF-κB pathway-mediated inflammatory response, reduce bone destruction, and regulate bacterial dysbiosis, demonstrating good therapeutic prospects for periodontitis.