Eucalyptol suppresses matrix metalloproteinase-9 expression through an extracellular signal-regulated kinase-dependent nuclear factor-kappa B pathway to exert anti-inflammatory effects in an acute lung inflammation model

Kim, Ka Young; Lee, Hui Su; Seol, Geun Hee

doi:10.1111/jphp.12407

Cited by 53 publications

(35 citation statements)

References 21 publications

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“…In our experiment, eucalyptol may have modulated IFN-c-dependent proinflammatory mechanisms. According to some authors, the anti-inflammatory effects of eucalyptol include the reduction of the expression of classic proinflammatory cytokines such as TNF-a and IL-1b in several models of inflammation (Santos et al 2001;Juergens et al 2004;Zhao et al 2014;Kim et al 2015). In a study by Santos et al (2001), eucalyptol improved D-galactosamine/lipopolysaccharide-induced liver injury by reducing TNF-c levels.…”

Section: Resultsmentioning

confidence: 99%

“…Its therapeutic role in inflammatory respiratory diseases, such as asthma and chronic obstructive pulmonary disease (COPD), is well established. The effect is associated with the anti-inflammatory (Kim et al 2015) and antioxidant (Rocha Caldas et al 2015) properties of eucalyptol, as shown by a number of preclinical studies. Another recent clinical study demonstrated the long-term benefits of treatment with eucalyptol in COPD prevention and asthma control (Juergens 2014).…”

Section: Introductionmentioning

confidence: 95%

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Acute and neuropathic orofacial antinociceptive effect of eucalyptol

et al. 2017

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Terpenes have a wide range of pharmacological properties, including antinociceptive action. The anti-inflammatory and antinociceptive effects of eucalyptol are well established. The purpose of this study was to evaluate the antinociceptive effect of eucalyptol on acute and neuropathic orofacial pain in rodent models. Acute orofacial and corneal nociception was induced with formalin, capsaicin, glutamate and hypertonic saline in mice. In another series, animals were pretreated with capsazepine or ruthenium red to evaluate the involvement of TRPV1 receptors in the effect of eucalyptol. In a separate experiment, perinasal tissue levels of IL-1β, TNF-α and IFN-γ were measured. Rats were pretreated with eucalyptol before induction of temporomandibular joint pain with formalin or mustard oil. In another experiment, rats were submitted to infraorbital nerve transection (IONX) to induce chronic pain, followed by induction of mechanical hypersensitivity using Von Frey hairs. Locomotor performance was evaluated with the open-field test, and molecular docking was conducted on the TRPV1 channel. Pretreatment with eucalyptol significantly reduced formalin-induced nociceptive behaviors in all mouse strains, but response was more homogenous in the Swiss strain. Eucalyptol produced antinociceptive effects in all tests. The effect was sensitive to capsazepine but not to ruthenium red. Moreover, eucalyptol significantly reduced IFN-γ levels. Matching the results of the experiment in vivo, the docking study indicated an interaction between eucalyptol and TRPV1. No locomotor activity changes were observed. Our study shows that eucalyptol may be a clinically relevant aid in the treatment of orofacial pain, possibly by acting as a TRPV1 channel antagonist.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 95%

Acute and neuropathic orofacial antinociceptive effect of eucalyptol

et al. 2017

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“…Eucalyptol is widely used as a treatment option for symptoms of the common cold, respiratory infections, pancreatitis, and colitis and for pain relief (Juergens, ; Seol & Kim, ). Studies have demonstrated that eucalyptol possess antioxidant activity, can suppress LPS‐induced IL‐1β and NO production, and reduce LPS‐induced NF‐κB activation (Kennedy‐Feitosa et al, ; Kim, Lee, & Seol, ; Li et al, ; Seol & Kim, ). Eucalyptol also inhibits TRPA1 channels and diminishes pain elicited by application of TRPA1 channel agonists to human skin (Takaishi et al, ).…”

Section: Introductionmentioning

confidence: 99%

Eucalyptol alleviates inflammation and pain responses in a mouse model of gout arthritis

Yin

Liu

Wang

et al. 2020

British J Pharmacology

127

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Background and Purpose: Gout arthritis, which is provoked by monosodium urate (MSU) crystal accumulation in the joint and periarticular tissues, induces severe pain and affects quality of life of the patients. Eucalyptol (1,8-cineol), the principal component in the essential oils of eucalyptus leaves, is known to possess anti-inflammatory and analgesic properties. We aimed to examine the therapeutic effects of eucalyptol on gout arthritis and related mechanisms. Experimental Approach: A mouse model of gout arthritis was established via MSU injection into the ankle joint. Ankle oedema, mechanical allodynia, neutrophil infiltration, oxidative stress, NLRP3 inflammasome, and TRPV1 expression were examined. Key Results: Eucalyptol attenuated MSU-induced mechanical allodynia and ankle oedema in dose-dependently, with effectiveness similar to indomethacin. Eucalyptol reduced inflammatory cell infiltrations in ankle tissues. Eucalyptol inhibited NLRP3 inflammasome activation and pro-inflammatory cytokine production induced by MSU in ankle tissues in vivo. Eucalyptol reduced oxidative stress induced by MSU in RAW264.7 cells in vitro as well as in ankle tissues in vivo, indicated by an increase in activities of antioxidant enzymes and reduction of ROS. Eucalyptol attenuated MSUinduced up-regulation of TRPV1 expression in ankle tissues and dorsal root ganglion neurons innervating the ankle. The in vivo effects of eucalyptol on ankle oedema, mechanical allodynia, NLRP3 inflammasome, IL-1β, and TRPV1 expression were mimicked by treating MSU-injected mice with antioxidants. Conclusion and Implications: Eucalyptol alleviates MSU-induced pain and inflammation via mechanisms possibly involving anti-oxidative effect. Eucalyptol and other antioxidants may represent promising therapeutic options for gout arthritis. Abbreviations: GSH-Px

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“…Several studies have shown that eucalyptol may also engage targets in the immune system (Juergens, ). Eucalyptol interfered with arachidonic acid metabolism in blood monocytes of asthma patients, inhibited LPS‐induced IL‐1β production in human monocytes, suppressed LPS‐induced production of nitric oxide in a macrophage cell line and diminished LPS‐induced expression, translocation and transcriptional activities of early growth response factor 1 and NF‐κB in human cell lines (Juergens et al, ,b; Zhou et al, ; Kim et al, ). Finally, eucalyptol also has antioxidant and antimicrobial activity that may contribute to its anti‐inflammatory effects in some pathological conditions (Keinan et al, ; Hendry et al, ; Sadlon and Lamson, ; Greiner et al, ).…”

Section: Introductionmentioning

confidence: 99%

Transient Receptor Potential Cation Channel Subfamily M Member 8 channels mediate the anti‐inflammatory effects of eucalyptol

Caceres

Liu

Jabba

et al. 2017

British J Pharmacology

105

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Among the pharmacological targets of eucalyptol, TRPM8 channels were essential for its anti-inflammatory effects in mice. Human TRPM8 channels are more sensitive to eucalyptol than rodent TRPM8 channels explaining the higher potency of eucalyptol in humans. Metabolites of eucalyptol could contribute to its anti-inflammatory effects. The development of more potent and selective TRPM8 agonists may yield novel anti-inflammatory agents.

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Eucalyptol suppresses matrix metalloproteinase-9 expression through an extracellular signal-regulated kinase-dependent nuclear factor-kappa B pathway to exert anti-inflammatory effects in an acute lung inflammation model

Abstract: Thus, eucalyptol may be a potentially important agent in the treatment of pulmonary inflammation.

Cited by 53 publications

References 21 publications

Acute and neuropathic orofacial antinociceptive effect of eucalyptol

Acute and neuropathic orofacial antinociceptive effect of eucalyptol

Eucalyptol alleviates inflammation and pain responses in a mouse model of gout arthritis

Transient Receptor Potential Cation Channel Subfamily M Member 8 channels mediate the anti‐inflammatory effects of eucalyptol

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