Abstract

Hinokitiol displays potent antimicrobial activity. It has been used in toothpaste and oral-care gel to improve the oral lichen planus and reduce halitosis. The aim of this study was to evaluate the antimicrobial activity of 3 different dental root canal sealers with hinokitiol (sealers+H) and their physical and biological effects. AH Plus (epoxy amine resin-based, AH), Apexit Plus (calcium-hydroxide-based, AP), and Canals (zinc-oxide-eugenol-based, CA), were used in this study. The original AH and CA exhibited strong anti-methicillin-resistant Staphylococcus aureus (anti-MRSA) activity, but AP did not. The setting time, working time, flowability, film thickness, and solubility of each sealer+0.2%H complied with ISO 6876:2001. CA+0.2%H exhibited high cytotoxicity, but the others sealers+0.2%H did not. Because hinokitiol combined with Zn2+ in CA creates a synergistic effect. The physical tests of AP+0.5%–1%H complied with ISO 6876:2001, improved antimicrobial activity, inhibited inflammation genes cyclooxygenase-2 (COX-2) and hypoxia-inducible factor-1α (HIF-1α) mRNA in MG-63 cells and human gingival fibroblasts (HGF), and down-regulated lysyl oxidase (LOX) mRNA of HGF. In summary, AH and CA demonstrated strong antimicrobial activity, but AP did not. Application of hinokitiol increases AH anti-MRSA activity should less than 0.2% for keep well flowability. AP+0.5%–1% hinokitiol exhibited strong physical, antibacterial, and anti-inflammation potentials, and inhibited S. aureus abscess formation. Applying an appreciable proportion of hinokitiol to epoxy-amine-resin-based and calcium-hydroxide-based root canal sealers is warranted, but the enhanced cytotoxicity and synergistic effect must be considered.

Highlights

  • Most endodontic therapy failures occur because of microleakage of irritants from diseased root canals [1]

  • Hypoxia-inducible factor-1a (HIF-1a), prostaglandins, and tumor necrosis factor-a (TNF-a) mediated inflammatory response have been inhibited by hinokitiol [14,15,16]

  • Hinokitiol inhibits oral bacteria growth The result of the kinetic analysis showed that A. actinomycetemcomitans and S. mutans growth were completely inhibited, but MRSA was partially inhibited when treated with 20 mg/mL of hinokitiol (Fig. 1)

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Summary

Introduction

Most endodontic therapy failures occur because of microleakage of irritants from diseased root canals [1]. The use of root canal filling materials with antibacterial activity is considered beneficial to reduce the number of remaining microorganisms and to eradicate infection. Studies have been conducted to assess the antimicrobial activity of various endodontic sealers [2,3], but few studies exist on the antimicrobial properties of sealers mixed with natural antibacterial compounds. Hinokitiol exhibits antibacterial, antifungal, antiviral, and insecticidal activities [4,5,6] and no developmental toxicity or carcinogenic effects have been observed [7,8]. Hinokitiol inhibits oral bacteria but exhibits low cytotoxicity to normal oral cells [9,10], and has been used in toothpaste and oral-care gel to improve the oral lichen planus and reduce halitosis [11,12,13]. Hypoxia-inducible factor-1a (HIF-1a), prostaglandins, and tumor necrosis factor-a (TNF-a) mediated inflammatory response have been inhibited by hinokitiol [14,15,16]

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