Pterostilbene complexed with cyclodextrin exerts antimicrobial and anti-inflammatory effects

Yi Rong Ivan Lim,Philip M Preshaw,Kai Soo Tan,Hai-Shu Lin,Marianne Meng Ann Ong,Lum Peng Lim

doi:10.1038/s41598-020-66031-8

Yi Rong Ivan Lim, Philip M Preshaw + Show 4 more

Open Access

https://doi.org/10.1038/s41598-020-66031-8

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Abstract

Resveratrol (RES) is a natural polyphenol with potential as an adjunctive therapeutic modality for periodontitis. However, its inferior pharmacokinetics and toxicity concerns about its commonly used solvent dimethyl sulfoxide (DMSO) hinder translation to clinical applicability. Our study aimed to investigate the comparative antimicrobial properties of RES and its analogues (pterostilbene [PTS], oxyresveratrol [OXY] and piceatannol [PIC]), utilizing 2-hydroxypropyl-β-cyclodextrin (HPβCD) as a solubiliser, which has a well-documented safety profile and FDA approval. These properties were investigated against Fusobacterium nucleatum, a key periodontal pathogen. PTS demonstrated the most potent antibacterial effects in HPβCD, with MIC > 60-fold lower than that of RES, OXY and PIC. In addition, PTS inhibited F. nucleatum biofilm formation. PTS exerted antimicrobial effects by eliciting leakage of cellular contents, leading to loss of bacterial cell viability. PTS also conferred immunomodulatory effects on F. nucleatum-challenged macrophages via upregulation of antioxidant pathways and inhibition of NF-κB activation. Given the superior antimicrobial potency of PTS against F. nucleatum compared to RES and other analogues, and coupled with its immunomodulatory properties, PTS complexed with HPβCD holds promise as a candidate nutraceutical for the adjunctive treatment of periodontitis.

Highlights

Resveratrol (RES) is a natural polyphenol with potential as an adjunctive therapeutic modality for periodontitis
When dissolved in HPβCD, PTS exhibited the highest antimicrobial potency against F. nucleatum, with minimum inhibitory concentration (MIC) and Minimum bactericidal concentration (MBC) values of 0.02 mg/ml and 0.04 mg/ml, respectively. This effect was attributed to PTS because HPβCD concentrations corresponding to the MIC and MBC of PTS did not affect the growth of F. nucleatum (Supplementary Fig. S1)
The pathogenesis of periodontitis involves a complex interplay between the dysbiotic microbial community and the resultant disproportionate host immune response, resulting in a loss of homeostasis[7]

Summary

Introduction

Resveratrol (RES) is a natural polyphenol with potential as an adjunctive therapeutic modality for periodontitis. Our study aimed to investigate the comparative antimicrobial properties of RES and its analogues (pterostilbene [PTS], oxyresveratrol [OXY] and piceatannol [PIC]), utilizing 2-hydroxypropyl-β-cyclodextrin (HPβCD) as a solubiliser, which has a well-documented safety profile and FDA approval. These properties were investigated against Fusobacterium nucleatum, a key periodontal pathogen. Researchers have investigated the use of adjunctive treatments including antibiotics and host-modulatory therapies[10,11] in the management of periodontitis, but concerns regarding risks of antibiotic resistance[12] preclude their widespread use In light of these considerations, RES may hold promise as a natural adjunctive therapeutic in the treatment of periodontitis. The need for a low concentration of DMSO limits the ability to dissolve critical amounts of RES required for meaningful biological activity

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