Anti-inflammatory effects of hinokitiol on human corneal epithelial cells: an in vitro study

Ye, Jianping; Yf, Xu; Lx, Lou; Jin, Ketao; Miao, Qi; X, Ye; Xi, Yue

doi:10.1038/eye.2015.62

Cited by 32 publications

(17 citation statements)

References 46 publications

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“…Moreover, poly (I:C) could be directly bound by the extracellular domain of CD14, thereby facilitating poly (I:C) uptake and enhancing TLR3 activation [10]. Poly (I:C) triggered TLR3 activation, followed by downstream inflammatory cascades have been reported in many corneal pathologies [11–13]. Recently, emerging evidences showed that TLR3 could also trigger the generation of reactive oxygen species (ROS), an essential secondary messenger that was required for NF-κB activation, leading to innate immune response [14].…”

Section: Introductionmentioning

confidence: 99%

Nerve growth factor inhibits TLR3-induced inflammatory cascades in human corneal epithelial cells

et al. 2019

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BackgroundIn herpes simplex epithelial keratitis, excessive TLR3-induced cellular responses after virus infection evoke inflammatory cascades that might be destructive to the host cornea. Nerve growth factor (NGF), a pluripotent neurotrophic factor with immune regulatory effect, was proved to be effective in Herpes simplex keratitis (HSK) treatment, although the detailed mechanisms remain unclear. This study aims to investigate the effects of NGF on modulating inflammatory responses triggered by TLR3 activation in human corneal epithelial cells (HCECs) in vitro.MethodsHCECs were stimulated with TLR3 agonist, poly(I:C), in the absence or presence of NGF. Cell viability and cytotoxicity were measured by a CCK-8 assay and LDH release assay, respectively. The activation of NF-κB signaling pathway was examined using immunofluorescence staining and western blotting. Levels of proinflammatory cytokines were determined by ELISA or RT-qPCR. ROS generation and 8-OHdG positive cells were examined by a fluorometric analysis.ResultsIt was shown that NGF significantly inhibited the generation of proinflammatory cytokines in HCECs triggered by TLR3 activation (P < 0.05), probably via suppressing NF-κB activation. NGF also impeded the upstream signal to initiate NF-κB activation by scavenging ROS by approximately 50% (P < 0.05). In addition, 8-OHdG positive cells were substantially attenuated by NGF treatment (P < 0.01).ConclusionsTaken together, this study indicates that NGF could inhibit TLR3-induced inflammatory cascades in HCECs, suggesting NGF as a potential therapeutic agent for HSK.

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Section: Introductionmentioning

confidence: 99%

Nerve growth factor inhibits TLR3-induced inflammatory cascades in human corneal epithelial cells

et al. 2019

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“…Although antibacterial treatment is an important approach against pneumonia, regulating excessive inflammation is equally essential [ 52 , 53 ]. Hinokitiol was previously shown to reduce the transcription of inflammatory cytokines from epithelial cells in vitro [ 6 , 54 ]. In this study, intratracheal administration of hinokitiol decreased the concentrations of cytokines and chemokines in BALF and serum.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2020

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Streptococcus pneumoniae is often isolated from patients with community-acquired pneumonia. Antibiotics are the primary line of treatment for pneumococcal pneumonia; however, rising antimicrobial resistance is becoming more prevalent. Hinokitiol, which is isolated from trees in the cypress family, has been demonstrated to exert antibacterial activity against S . pneumoniae in vitro regardless of antimicrobial resistance. In this study, the efficacy of hinokitiol was investigated in a mouse pneumonia model. Male 8-week-old BALB/c mice were intratracheally infected with S . pneumoniae strains D39 (antimicrobial susceptible) and NU4471 (macrolide resistant). After 1 h, hinokitiol was injected via the tracheal route. Hinokitiol significantly decreased the number of S . pneumoniae in the bronchoalveolar lavage fluid (BALF) and the concentration of pneumococcal DNA in the serum, regardless of whether bacteria were resistant or susceptible to macrolides. In addition, hinokitiol decreased the infiltration of neutrophils in the lungs, as well as the concentration of inflammatory cytokines in the BALF and serum. Repeated hinokitiol injection at 18 h intervals showed downward trend in the number of S . pneumoniae in the BALF and the concentration of S . pneumoniae DNA in the serum with the number of hinokitiol administrations. These findings suggest that hinokitiol reduced bacterial load and suppressed excessive host immune response in the pneumonia mouse model. Accordingly, hinokitiol warrants further exploration as a potential candidate for the treatment of pneumococcal pneumonia.

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“…Hinokitiol (β-thujaplicin) is a naturally occurring monoterpenoid found in the wooden part of trees in the Cupressaceae family. It is a tropolone derivative and is widely used in oral care and therapeutic products for its potent, broad-spectrum antiviral, antimicrobial [4] , antifungal, anti-inflammatory [5] , [6] , and anticancer properties [7] . Additionally, it has been approved as a food additive and does not accumulate in the body.…”

Section: Background To Hypothesismentioning

confidence: 99%

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

Hoang

Han

2020

Medical Hypotheses

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Zinc and the combination with zinc ionophore have been reported in basic research and several clinical investigations as a potentially viable and economical preventive and therapeutic options for COVID-19 treatment. Zinc is a vital microelement that actively supports respiratory epithelium barrier integrity, innate and adaptive immune functions, and inflammatory regulations. Moreover, zinc may also prevent viral entry, suppress viral replication, and mitigate the damages due to oxidative stress and hyperinflammatory reaction in patients with respiratory infections. Hinokitiol (β-thujaplicin) is a natural monoterpenoid and is considered as a safe zinc ionophore to help zinc transport into cells. It has been widely used in skin and oral care, and therapeutic products for its potent antiviral, antimicrobial, antifungal, anti-inflammatory, and anticancer applications. The ongoing COVID-19 pandemic and the significant morbidity and mortality exist in the high-risk group of patients associated with other respiratory infections such as influenza, respiratory syncytial virus, and dengue fever. There is an urgent need for the development of inexpensive, safe, and effective therapeutics to prevent and treat these viral infections. Considering that hydroxychloroquine (HCQ), the most studied zinc ionophore drug for COVID-19, is linked to potentially serious side effects, we propose the implementation of hinokitiol as a zinc ionophore and anti-infective agent for the prevention and treatment of COVID-19 and other viral infections.

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Anti-inflammatory effects of hinokitiol on human corneal epithelial cells: an in vitro study

Abstract: Purpose This study assessed the antiinflammatory effect and mechanism of action of hinokitiol in human corneal epithelial (HCE) cells.

Cited by 32 publications

References 46 publications

Nerve growth factor inhibits TLR3-induced inflammatory cascades in human corneal epithelial cells

Nerve growth factor inhibits TLR3-induced inflammatory cascades in human corneal epithelial cells

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

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

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