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Area of Science:

  • Periodontal disease research
  • Natural product chemistry
  • Antimicrobial drug discovery

Background:

  • Resveratrol (RES) shows promise for periodontitis but has poor pharmacokinetics and relies on toxic solvents.
  • Dimethyl sulfoxide (DMSO) is a common solvent for RES but raises toxicity concerns for clinical use.

Purpose of the Study:

  • To compare the antimicrobial properties of RES analogues (pterostilbene [PTS], oxyresveratrol [OXY], piceatannol [PIC]) against Fusobacterium nucleatum.
  • To evaluate these compounds using 2-hydroxypropyl-β-cyclodextrin (HPβCD) as a safe and FDA-approved solubilizer.
  • To assess the immunomodulatory effects of PTS on macrophages challenged with F. nucleatum.

Main Methods:

  • Minimum inhibitory concentration (MIC) assays were performed for RES and its analogues against F. nucleatum.
  • Biofilm formation inhibition by PTS was assessed.
  • Macrophage responses (antioxidant pathways, NF-κB activation) were analyzed after F. nucleatum challenge and PTS treatment.

Main Results:

  • Pterostilbene (PTS) exhibited significantly greater antimicrobial potency against F. nucleatum (MIC >60-fold lower than RES, OXY, PIC) when solubilized with HPβCD.
  • PTS effectively inhibited F. nucleatum biofilm formation.
  • PTS demonstrated immunomodulatory effects by upregulating antioxidant pathways and inhibiting NF-κB activation in challenged macrophages.

Conclusions:

  • Pterostilbene (PTS) complexed with HPβCD is a potent antimicrobial agent against Fusobacterium nucleatum, surpassing resveratrol and other analogues.
  • PTS possesses beneficial immunomodulatory properties relevant to periodontitis treatment.
  • PTS-HPβCD holds promise as a safe and effective nutraceutical for adjunctive periodontitis therapy.