Antibacterial activity of hinokitiol against both antibiotic‐resistant and ‐susceptible pathogenic bacteria that predominate in the oral cavity and upper airways

Abstract

Hinokitiol, a component of the essential oil isolated from Cupressaceae, possesses antibacterial and antifungal activities and has been used in oral care products. In this study, the antibacterial activities of hinokitiol toward various oral, nasal and nasopharyngeal pathogenic bacteria, including Streptococcus mutans, Streptococcus sobrinus, Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Prevotella intermedia, Fusobacterium nucleatum, methicillin‐resistant and ‐susceptible Staphylococcus aureus, antibiotic‐resistant and ‐susceptible Streptococcus pneumoniae, and Streptococcus pyogenes were examined. Growth of all these bacterial strains was significantly inhibited by hinokitiol, minimal inhibitory concentrations of hinokitiol against S. mutans, S. sobrinus, P. gingivalis, P. intermedia, A. actinomycetemcomitans, F. nucleatum, methicillin‐resistant S. aureus, methicillin‐susceptible S. aureus, antibiotic‐resistant S. pneumoniae isolates, antibiotic‐susceptible S. pneumoniae, and S. pyogenes being 0.3, 1.0, 1.0, 30, 0.5, 50, 50, 30, 0.3–1.0, 0.5, and 0.3 μg/mL, respectively. Additionally, with the exception of P. gingivalis, hinokitiol exerted bactericidal effects against all bacterial strains 1 hr after exposure. Hinokitiol did not display any significant cytotoxicity toward the human gingival epithelial cell line Ca9‐22, pharyngeal epithelial cell line Detroit 562, human umbilical vein endothelial cells, or human gingival fibroblasts, with the exception of treatment with 500 μg/mL hinokitiol, which decreased numbers of viable Ca9‐22 cells and gingival fibroblasts by 13% and 12%, respectively. These results suggest that hinokitiol exhibits antibacterial activity against a broad spectrum of pathogenic bacteria and has low cytotoxicity towards human epithelial cells.

Treatment of severe pneumonia by hinokitiol in a murine antimicrobial-resistant pneumococcal pneumonia model

“…Our previous in vitro study showed that 0.3 μg/mL hinokitiol exerted antibacterial effect against S . pneumoniae regardless of antimicrobial resistance [ 10 ]. Here, compared with PBS injection, intratracheal administration of 500 μg/mL hinokitiol in a pneumococcal pneumonia mouse model decreased inflammatory cell migration and prevented destruction of alveolar tissue ( Fig 2 ).…”

“…An important aspect when selecting a drug is to evaluate and compare its therapeutic index [ 34 ]. Although hinokitiol exhibits antibacterial effect against various pathogenic organisms [ 10 ], dosages above 12.7 and 14.8 mg/kg/day in male and female rats, respectively, have been shown to produce systemic side effects such as chronic toxicity [ 35 ]. Based on our observations and these values, intraperitoneal injection of 10 mg/kg hinokitiol would be the maximum concentration for systemic administration in mice.…”

“…Hinokitiol has been shown to inhibit the growth of antimicrobial-resistant organisms in vitro , such as methicillin-resistant Staphylococcus aureus and multidrug-resistant S . pneumoniae [ 10 , 27 , 47 ]. In this study, intratracheal administration of hinokitiol suppressed bacterial pneumonia induced by macrolide-resistant pneumococci.…”

A possible application of hinokitiol as a natural zinc ionophore and anti-infective agent for the prevention and treatment of COVID-19 and viral infections

“…Hinokitiol has potent antimicrobial activity against many bacteria and fungi, including antibiotic-resistant pathogens [31] , [32] . It inhibited the growth of common human pathogens such as Escherichia coli, Streptococcus pneumonia, Streptococcus mutans, and Staphylococcus Aureus when inoculated these bacteria in optimal growth conditions [33] . The effective amount (50µg/ml) was only one 20th against the dose to show the bactericidal activity, which was the same dose recommended for fragrance usage [34] .…”

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“…Considering this role of infections can be considered, control and elimination of the microorganisms present in the pulp cavity 44 . A study was made of the antimicrobial capacity of dental cement in bacterial cultures of S. mutans, S. pyogenes, S.aureus, E. faecalis, and E. coli showed that Zinc phosphate cement (CPZn) produced inhibition halos on S. pyogenes, S. mutans, and S. aureus microorganisms 45 . The present study showed that the cement inhibited S.a, P.g, F.n, A.a with larger halos and antimicrobial activity than those of Zinc phosphate cement (CPZn).…”