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Sveneric Jordt - One of the best experts on this subject based on the ideXlab platform.
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transient receptor potential cation channel subfamily m member 8 channels mediate the anti inflammatory effects of Eucalyptol
British Journal of Pharmacology, 2017Co-Authors: Ana Isabel Caceres, Boyi Liu, Sairam V Jabba, Satyanarayana Achanta, John B Morris, Sveneric JordtAbstract:Background and Purpose Eucalyptol (1,8-cineol), the major ingredient in the essential oil of eucalyptus leaves and other medicinal plants, has long been known for its anti-inflammatory properties. Eucalyptol interacts with the TRP cation channels among other targets, but it is unclear which of these mediates its anti-inflammatory effects. Experimental Approach Effects of Eucalyptol were compared in wild-type and TRPM8 channel-deficient mice in two different models: footpad inflammation elicited by complete Freund's adjuvant (CFA) and pulmonary inflammation following administration of LPS. Oedema formation, behavioural inflammatory pain responses, leukocyte infiltration, enzyme activities and cytokine and chemokine levels were measured. Key Results In the CFA model, Eucalyptol strongly attenuated oedema and mechanical allodynia and reduced levels of inflammatory cytokines (IL-1β, TNF-α and IL-6), effects comparable with those of ibuprofen. In the LPS model of pulmonary inflammation, Eucalyptol treatment diminished leukocyte infiltration, myeloperoxidase activity and production of TNF-α, IL-1β, IFN-γ and IL-6. Genetic deletion of TRPM8 channels abolished the anti-inflammatory effects of Eucalyptol in both models. Eucalyptol was at least sixfold more potent on human, than on mouse TRPM8 channels. A metabolite of Eucalyptol, 2-hydroxy-1,8-cineol, also activated human TRPM8 channels. Conclusion and Implications 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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transient receptor potential cation channel subfamily m member 8 channels mediate the anti inflammatory effects of Eucalyptol
British Journal of Pharmacology, 2017Co-Authors: Ana Isabel Caceres, Boyi Liu, Sairam V Jabba, Satyanarayana Achanta, John B Morris, Sveneric JordtAbstract:SummaryBackground and Purpose Eucalyptol (1,8-cineol), the major ingredient in the essential oil of the eucalyptus leaves and other medicinal plants, has long been known for its anti-inflammatory properties. Eucalyptol interacts with Transient Receptor Potential (TRP) ion channels among other targets, but it is unclear which of these mediates its anti-inflammatory effects. Experimental Approach The effects of Eucalyptol were compared in wild-type and TRPM8-deficient mice in two different models: Footpad inflammation elicited by Complete Freund's Adjuvant (CFA) and pulmonary inflammation following administration of lipopolysaccharide (LPS). Edema formation, behavioral inflammatory pain responses, leukocyte infiltration, enzyme activities and cytokine/chemokine levels were compared. Key Results In the CFA model, Eucalyptol strongly attenuated edema and mechanical allodynia and reduced levels of inflammatory cytokines (IL-1β, TNF-α, IL-6), effects comparable to those of ibuprofen. In the LPS model of pulmonary inflammation, Eucalyptol treatment diminished leukocyte infiltration, myeloperoxidase activity and production of TNF-α, IL-1β, IFN-γ and IL-6. Genetic deletion of TRPM8 completely abolished the anti-inflammatory effects of Eucalyptol in both models. Eucalyptol is at least 6-fold more potent on human TRPM8 than on mouse TRPM8. A metabolite of Eucalyptol, 2-hydroxy-1,8-cineol, also activated human TRPM8. Conclusion and Implications Among the pharmacological targets of Eucalyptol TRPM8 is essential for its anti-inflammatory effects in mice. The much higher sensitivity of human TRPM8 to Eucalyptol compared to the rodent orthologues explains the higher potency of Eucalyptol in humans. Metabolites of Eucalyptol likely contribute to the anti-inflammatory effects. The development of more potent and selective TRPM8 agonists may yield novel anti-inflammatory therapeutics.
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the anti inflammatory effects of Eucalyptol in a mouse model of lps induced pulmonary inflammation are mediated by trpm8
European Respiratory Journal, 2016Co-Authors: Anabel De Caceres Bustos, Boyi Liu, Sairam V Jabba, John B Morris, Sveneric JordtAbstract:Eucalyptol (1,8-cineol) has long been known for its anti-inflammatory properties. It interacts with Transient Receptor Potential (TRP) ion channels among other targets, but it is unclear which of these mediates its anti-inflammatory effects. In this work, the effects of Eucalyptol were compared in WT and TRPM8-deficient mice in a model of pulmonary inflammation following intranasal administration of lipopolysaccharide (LPS). LPS, a component of Gram-negative bacterial cell walls, plays a major role in acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). 24 hours after LPS intranasal instillation, lungs and bronchoalvelolar lavage (BAL) from Eucalyptol treated and untreated TRPM8 KO and WT mice were collected and analyzed. This study shows that Eucalyptol treatment diminishes leukocyte infiltration, myeloperoxidase activity and cytokine production in the lung. Genetic deletion of TRPM8 abolishes the anti-inflammatory effects of Eucalyptol in the LPS model. Eucalyptol is at least 30-fold more potent on human TRPM8 than on mouse TRPM8, and a metabolite of Eucalyptol, 2-hydroxy-1,8-cineol, also activates human TRPM8. Our data show that among the pharmacological targets of Eucalyptol, TRPM8 is essential for its anti-inflammatory effects.The development of more potent and selective TRPM8 agonists may yield novel anti-inflammatory pharmacological treatments with lower toxicity and adverse effects than the current available options.
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trpm8 mediates the anti inflammatory effects of Eucalyptol in a mouse model of lps induced pulmonary inflammation
The FASEB Journal, 2016Co-Authors: Ana Isabel Caceres, Boyi Liu, Sairam V Jabba, John B Morris, Sveneric JordtAbstract:Eucalyptol (1,8-cineol), the major ingredient in the essential oil of the eucalyptus leaves and other medicinal plants, has long been known for its anti-inflammatory properties. Eucalyptol interact...
Boyi Liu - One of the best experts on this subject based on the ideXlab platform.
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Eucalyptol alleviates inflammation and pain responses in a mouse model of gout arthritis
British Journal of Pharmacology, 2020Co-Authors: Chengyu Yin, Boyu Liu, Ping Wang, Xiaoli Zheng, Yan Tai, Chuan Wang, Boyi LiuAbstract: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 MSU-induced 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.
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transient receptor potential cation channel subfamily m member 8 channels mediate the anti inflammatory effects of Eucalyptol
British Journal of Pharmacology, 2017Co-Authors: Ana Isabel Caceres, Boyi Liu, Sairam V Jabba, Satyanarayana Achanta, John B Morris, Sveneric JordtAbstract:Background and Purpose Eucalyptol (1,8-cineol), the major ingredient in the essential oil of eucalyptus leaves and other medicinal plants, has long been known for its anti-inflammatory properties. Eucalyptol interacts with the TRP cation channels among other targets, but it is unclear which of these mediates its anti-inflammatory effects. Experimental Approach Effects of Eucalyptol were compared in wild-type and TRPM8 channel-deficient mice in two different models: footpad inflammation elicited by complete Freund's adjuvant (CFA) and pulmonary inflammation following administration of LPS. Oedema formation, behavioural inflammatory pain responses, leukocyte infiltration, enzyme activities and cytokine and chemokine levels were measured. Key Results In the CFA model, Eucalyptol strongly attenuated oedema and mechanical allodynia and reduced levels of inflammatory cytokines (IL-1β, TNF-α and IL-6), effects comparable with those of ibuprofen. In the LPS model of pulmonary inflammation, Eucalyptol treatment diminished leukocyte infiltration, myeloperoxidase activity and production of TNF-α, IL-1β, IFN-γ and IL-6. Genetic deletion of TRPM8 channels abolished the anti-inflammatory effects of Eucalyptol in both models. Eucalyptol was at least sixfold more potent on human, than on mouse TRPM8 channels. A metabolite of Eucalyptol, 2-hydroxy-1,8-cineol, also activated human TRPM8 channels. Conclusion and Implications 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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transient receptor potential cation channel subfamily m member 8 channels mediate the anti inflammatory effects of Eucalyptol
British Journal of Pharmacology, 2017Co-Authors: Ana Isabel Caceres, Boyi Liu, Sairam V Jabba, Satyanarayana Achanta, John B Morris, Sveneric JordtAbstract:SummaryBackground and Purpose Eucalyptol (1,8-cineol), the major ingredient in the essential oil of the eucalyptus leaves and other medicinal plants, has long been known for its anti-inflammatory properties. Eucalyptol interacts with Transient Receptor Potential (TRP) ion channels among other targets, but it is unclear which of these mediates its anti-inflammatory effects. Experimental Approach The effects of Eucalyptol were compared in wild-type and TRPM8-deficient mice in two different models: Footpad inflammation elicited by Complete Freund's Adjuvant (CFA) and pulmonary inflammation following administration of lipopolysaccharide (LPS). Edema formation, behavioral inflammatory pain responses, leukocyte infiltration, enzyme activities and cytokine/chemokine levels were compared. Key Results In the CFA model, Eucalyptol strongly attenuated edema and mechanical allodynia and reduced levels of inflammatory cytokines (IL-1β, TNF-α, IL-6), effects comparable to those of ibuprofen. In the LPS model of pulmonary inflammation, Eucalyptol treatment diminished leukocyte infiltration, myeloperoxidase activity and production of TNF-α, IL-1β, IFN-γ and IL-6. Genetic deletion of TRPM8 completely abolished the anti-inflammatory effects of Eucalyptol in both models. Eucalyptol is at least 6-fold more potent on human TRPM8 than on mouse TRPM8. A metabolite of Eucalyptol, 2-hydroxy-1,8-cineol, also activated human TRPM8. Conclusion and Implications Among the pharmacological targets of Eucalyptol TRPM8 is essential for its anti-inflammatory effects in mice. The much higher sensitivity of human TRPM8 to Eucalyptol compared to the rodent orthologues explains the higher potency of Eucalyptol in humans. Metabolites of Eucalyptol likely contribute to the anti-inflammatory effects. The development of more potent and selective TRPM8 agonists may yield novel anti-inflammatory therapeutics.
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the anti inflammatory effects of Eucalyptol in a mouse model of lps induced pulmonary inflammation are mediated by trpm8
European Respiratory Journal, 2016Co-Authors: Anabel De Caceres Bustos, Boyi Liu, Sairam V Jabba, John B Morris, Sveneric JordtAbstract:Eucalyptol (1,8-cineol) has long been known for its anti-inflammatory properties. It interacts with Transient Receptor Potential (TRP) ion channels among other targets, but it is unclear which of these mediates its anti-inflammatory effects. In this work, the effects of Eucalyptol were compared in WT and TRPM8-deficient mice in a model of pulmonary inflammation following intranasal administration of lipopolysaccharide (LPS). LPS, a component of Gram-negative bacterial cell walls, plays a major role in acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). 24 hours after LPS intranasal instillation, lungs and bronchoalvelolar lavage (BAL) from Eucalyptol treated and untreated TRPM8 KO and WT mice were collected and analyzed. This study shows that Eucalyptol treatment diminishes leukocyte infiltration, myeloperoxidase activity and cytokine production in the lung. Genetic deletion of TRPM8 abolishes the anti-inflammatory effects of Eucalyptol in the LPS model. Eucalyptol is at least 30-fold more potent on human TRPM8 than on mouse TRPM8, and a metabolite of Eucalyptol, 2-hydroxy-1,8-cineol, also activates human TRPM8. Our data show that among the pharmacological targets of Eucalyptol, TRPM8 is essential for its anti-inflammatory effects.The development of more potent and selective TRPM8 agonists may yield novel anti-inflammatory pharmacological treatments with lower toxicity and adverse effects than the current available options.
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trpm8 mediates the anti inflammatory effects of Eucalyptol in a mouse model of lps induced pulmonary inflammation
The FASEB Journal, 2016Co-Authors: Ana Isabel Caceres, Boyi Liu, Sairam V Jabba, John B Morris, Sveneric JordtAbstract:Eucalyptol (1,8-cineol), the major ingredient in the essential oil of the eucalyptus leaves and other medicinal plants, has long been known for its anti-inflammatory properties. Eucalyptol interact...
Ana Isabel Caceres - One of the best experts on this subject based on the ideXlab platform.
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transient receptor potential cation channel subfamily m member 8 channels mediate the anti inflammatory effects of Eucalyptol
British Journal of Pharmacology, 2017Co-Authors: Ana Isabel Caceres, Boyi Liu, Sairam V Jabba, Satyanarayana Achanta, John B Morris, Sveneric JordtAbstract:Background and Purpose Eucalyptol (1,8-cineol), the major ingredient in the essential oil of eucalyptus leaves and other medicinal plants, has long been known for its anti-inflammatory properties. Eucalyptol interacts with the TRP cation channels among other targets, but it is unclear which of these mediates its anti-inflammatory effects. Experimental Approach Effects of Eucalyptol were compared in wild-type and TRPM8 channel-deficient mice in two different models: footpad inflammation elicited by complete Freund's adjuvant (CFA) and pulmonary inflammation following administration of LPS. Oedema formation, behavioural inflammatory pain responses, leukocyte infiltration, enzyme activities and cytokine and chemokine levels were measured. Key Results In the CFA model, Eucalyptol strongly attenuated oedema and mechanical allodynia and reduced levels of inflammatory cytokines (IL-1β, TNF-α and IL-6), effects comparable with those of ibuprofen. In the LPS model of pulmonary inflammation, Eucalyptol treatment diminished leukocyte infiltration, myeloperoxidase activity and production of TNF-α, IL-1β, IFN-γ and IL-6. Genetic deletion of TRPM8 channels abolished the anti-inflammatory effects of Eucalyptol in both models. Eucalyptol was at least sixfold more potent on human, than on mouse TRPM8 channels. A metabolite of Eucalyptol, 2-hydroxy-1,8-cineol, also activated human TRPM8 channels. Conclusion and Implications 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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transient receptor potential cation channel subfamily m member 8 channels mediate the anti inflammatory effects of Eucalyptol
British Journal of Pharmacology, 2017Co-Authors: Ana Isabel Caceres, Boyi Liu, Sairam V Jabba, Satyanarayana Achanta, John B Morris, Sveneric JordtAbstract:SummaryBackground and Purpose Eucalyptol (1,8-cineol), the major ingredient in the essential oil of the eucalyptus leaves and other medicinal plants, has long been known for its anti-inflammatory properties. Eucalyptol interacts with Transient Receptor Potential (TRP) ion channels among other targets, but it is unclear which of these mediates its anti-inflammatory effects. Experimental Approach The effects of Eucalyptol were compared in wild-type and TRPM8-deficient mice in two different models: Footpad inflammation elicited by Complete Freund's Adjuvant (CFA) and pulmonary inflammation following administration of lipopolysaccharide (LPS). Edema formation, behavioral inflammatory pain responses, leukocyte infiltration, enzyme activities and cytokine/chemokine levels were compared. Key Results In the CFA model, Eucalyptol strongly attenuated edema and mechanical allodynia and reduced levels of inflammatory cytokines (IL-1β, TNF-α, IL-6), effects comparable to those of ibuprofen. In the LPS model of pulmonary inflammation, Eucalyptol treatment diminished leukocyte infiltration, myeloperoxidase activity and production of TNF-α, IL-1β, IFN-γ and IL-6. Genetic deletion of TRPM8 completely abolished the anti-inflammatory effects of Eucalyptol in both models. Eucalyptol is at least 6-fold more potent on human TRPM8 than on mouse TRPM8. A metabolite of Eucalyptol, 2-hydroxy-1,8-cineol, also activated human TRPM8. Conclusion and Implications Among the pharmacological targets of Eucalyptol TRPM8 is essential for its anti-inflammatory effects in mice. The much higher sensitivity of human TRPM8 to Eucalyptol compared to the rodent orthologues explains the higher potency of Eucalyptol in humans. Metabolites of Eucalyptol likely contribute to the anti-inflammatory effects. The development of more potent and selective TRPM8 agonists may yield novel anti-inflammatory therapeutics.
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trpm8 mediates the anti inflammatory effects of Eucalyptol in a mouse model of lps induced pulmonary inflammation
The FASEB Journal, 2016Co-Authors: Ana Isabel Caceres, Boyi Liu, Sairam V Jabba, John B Morris, Sveneric JordtAbstract:Eucalyptol (1,8-cineol), the major ingredient in the essential oil of the eucalyptus leaves and other medicinal plants, has long been known for its anti-inflammatory properties. Eucalyptol interact...
Sairam V Jabba - One of the best experts on this subject based on the ideXlab platform.
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transient receptor potential cation channel subfamily m member 8 channels mediate the anti inflammatory effects of Eucalyptol
British Journal of Pharmacology, 2017Co-Authors: Ana Isabel Caceres, Boyi Liu, Sairam V Jabba, Satyanarayana Achanta, John B Morris, Sveneric JordtAbstract:Background and Purpose Eucalyptol (1,8-cineol), the major ingredient in the essential oil of eucalyptus leaves and other medicinal plants, has long been known for its anti-inflammatory properties. Eucalyptol interacts with the TRP cation channels among other targets, but it is unclear which of these mediates its anti-inflammatory effects. Experimental Approach Effects of Eucalyptol were compared in wild-type and TRPM8 channel-deficient mice in two different models: footpad inflammation elicited by complete Freund's adjuvant (CFA) and pulmonary inflammation following administration of LPS. Oedema formation, behavioural inflammatory pain responses, leukocyte infiltration, enzyme activities and cytokine and chemokine levels were measured. Key Results In the CFA model, Eucalyptol strongly attenuated oedema and mechanical allodynia and reduced levels of inflammatory cytokines (IL-1β, TNF-α and IL-6), effects comparable with those of ibuprofen. In the LPS model of pulmonary inflammation, Eucalyptol treatment diminished leukocyte infiltration, myeloperoxidase activity and production of TNF-α, IL-1β, IFN-γ and IL-6. Genetic deletion of TRPM8 channels abolished the anti-inflammatory effects of Eucalyptol in both models. Eucalyptol was at least sixfold more potent on human, than on mouse TRPM8 channels. A metabolite of Eucalyptol, 2-hydroxy-1,8-cineol, also activated human TRPM8 channels. Conclusion and Implications 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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transient receptor potential cation channel subfamily m member 8 channels mediate the anti inflammatory effects of Eucalyptol
British Journal of Pharmacology, 2017Co-Authors: Ana Isabel Caceres, Boyi Liu, Sairam V Jabba, Satyanarayana Achanta, John B Morris, Sveneric JordtAbstract:SummaryBackground and Purpose Eucalyptol (1,8-cineol), the major ingredient in the essential oil of the eucalyptus leaves and other medicinal plants, has long been known for its anti-inflammatory properties. Eucalyptol interacts with Transient Receptor Potential (TRP) ion channels among other targets, but it is unclear which of these mediates its anti-inflammatory effects. Experimental Approach The effects of Eucalyptol were compared in wild-type and TRPM8-deficient mice in two different models: Footpad inflammation elicited by Complete Freund's Adjuvant (CFA) and pulmonary inflammation following administration of lipopolysaccharide (LPS). Edema formation, behavioral inflammatory pain responses, leukocyte infiltration, enzyme activities and cytokine/chemokine levels were compared. Key Results In the CFA model, Eucalyptol strongly attenuated edema and mechanical allodynia and reduced levels of inflammatory cytokines (IL-1β, TNF-α, IL-6), effects comparable to those of ibuprofen. In the LPS model of pulmonary inflammation, Eucalyptol treatment diminished leukocyte infiltration, myeloperoxidase activity and production of TNF-α, IL-1β, IFN-γ and IL-6. Genetic deletion of TRPM8 completely abolished the anti-inflammatory effects of Eucalyptol in both models. Eucalyptol is at least 6-fold more potent on human TRPM8 than on mouse TRPM8. A metabolite of Eucalyptol, 2-hydroxy-1,8-cineol, also activated human TRPM8. Conclusion and Implications Among the pharmacological targets of Eucalyptol TRPM8 is essential for its anti-inflammatory effects in mice. The much higher sensitivity of human TRPM8 to Eucalyptol compared to the rodent orthologues explains the higher potency of Eucalyptol in humans. Metabolites of Eucalyptol likely contribute to the anti-inflammatory effects. The development of more potent and selective TRPM8 agonists may yield novel anti-inflammatory therapeutics.
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the anti inflammatory effects of Eucalyptol in a mouse model of lps induced pulmonary inflammation are mediated by trpm8
European Respiratory Journal, 2016Co-Authors: Anabel De Caceres Bustos, Boyi Liu, Sairam V Jabba, John B Morris, Sveneric JordtAbstract:Eucalyptol (1,8-cineol) has long been known for its anti-inflammatory properties. It interacts with Transient Receptor Potential (TRP) ion channels among other targets, but it is unclear which of these mediates its anti-inflammatory effects. In this work, the effects of Eucalyptol were compared in WT and TRPM8-deficient mice in a model of pulmonary inflammation following intranasal administration of lipopolysaccharide (LPS). LPS, a component of Gram-negative bacterial cell walls, plays a major role in acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). 24 hours after LPS intranasal instillation, lungs and bronchoalvelolar lavage (BAL) from Eucalyptol treated and untreated TRPM8 KO and WT mice were collected and analyzed. This study shows that Eucalyptol treatment diminishes leukocyte infiltration, myeloperoxidase activity and cytokine production in the lung. Genetic deletion of TRPM8 abolishes the anti-inflammatory effects of Eucalyptol in the LPS model. Eucalyptol is at least 30-fold more potent on human TRPM8 than on mouse TRPM8, and a metabolite of Eucalyptol, 2-hydroxy-1,8-cineol, also activates human TRPM8. Our data show that among the pharmacological targets of Eucalyptol, TRPM8 is essential for its anti-inflammatory effects.The development of more potent and selective TRPM8 agonists may yield novel anti-inflammatory pharmacological treatments with lower toxicity and adverse effects than the current available options.
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trpm8 mediates the anti inflammatory effects of Eucalyptol in a mouse model of lps induced pulmonary inflammation
The FASEB Journal, 2016Co-Authors: Ana Isabel Caceres, Boyi Liu, Sairam V Jabba, John B Morris, Sveneric JordtAbstract:Eucalyptol (1,8-cineol), the major ingredient in the essential oil of the eucalyptus leaves and other medicinal plants, has long been known for its anti-inflammatory properties. Eucalyptol interact...
John B Morris - One of the best experts on this subject based on the ideXlab platform.
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transient receptor potential cation channel subfamily m member 8 channels mediate the anti inflammatory effects of Eucalyptol
British Journal of Pharmacology, 2017Co-Authors: Ana Isabel Caceres, Boyi Liu, Sairam V Jabba, Satyanarayana Achanta, John B Morris, Sveneric JordtAbstract:Background and Purpose Eucalyptol (1,8-cineol), the major ingredient in the essential oil of eucalyptus leaves and other medicinal plants, has long been known for its anti-inflammatory properties. Eucalyptol interacts with the TRP cation channels among other targets, but it is unclear which of these mediates its anti-inflammatory effects. Experimental Approach Effects of Eucalyptol were compared in wild-type and TRPM8 channel-deficient mice in two different models: footpad inflammation elicited by complete Freund's adjuvant (CFA) and pulmonary inflammation following administration of LPS. Oedema formation, behavioural inflammatory pain responses, leukocyte infiltration, enzyme activities and cytokine and chemokine levels were measured. Key Results In the CFA model, Eucalyptol strongly attenuated oedema and mechanical allodynia and reduced levels of inflammatory cytokines (IL-1β, TNF-α and IL-6), effects comparable with those of ibuprofen. In the LPS model of pulmonary inflammation, Eucalyptol treatment diminished leukocyte infiltration, myeloperoxidase activity and production of TNF-α, IL-1β, IFN-γ and IL-6. Genetic deletion of TRPM8 channels abolished the anti-inflammatory effects of Eucalyptol in both models. Eucalyptol was at least sixfold more potent on human, than on mouse TRPM8 channels. A metabolite of Eucalyptol, 2-hydroxy-1,8-cineol, also activated human TRPM8 channels. Conclusion and Implications 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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transient receptor potential cation channel subfamily m member 8 channels mediate the anti inflammatory effects of Eucalyptol
British Journal of Pharmacology, 2017Co-Authors: Ana Isabel Caceres, Boyi Liu, Sairam V Jabba, Satyanarayana Achanta, John B Morris, Sveneric JordtAbstract:SummaryBackground and Purpose Eucalyptol (1,8-cineol), the major ingredient in the essential oil of the eucalyptus leaves and other medicinal plants, has long been known for its anti-inflammatory properties. Eucalyptol interacts with Transient Receptor Potential (TRP) ion channels among other targets, but it is unclear which of these mediates its anti-inflammatory effects. Experimental Approach The effects of Eucalyptol were compared in wild-type and TRPM8-deficient mice in two different models: Footpad inflammation elicited by Complete Freund's Adjuvant (CFA) and pulmonary inflammation following administration of lipopolysaccharide (LPS). Edema formation, behavioral inflammatory pain responses, leukocyte infiltration, enzyme activities and cytokine/chemokine levels were compared. Key Results In the CFA model, Eucalyptol strongly attenuated edema and mechanical allodynia and reduced levels of inflammatory cytokines (IL-1β, TNF-α, IL-6), effects comparable to those of ibuprofen. In the LPS model of pulmonary inflammation, Eucalyptol treatment diminished leukocyte infiltration, myeloperoxidase activity and production of TNF-α, IL-1β, IFN-γ and IL-6. Genetic deletion of TRPM8 completely abolished the anti-inflammatory effects of Eucalyptol in both models. Eucalyptol is at least 6-fold more potent on human TRPM8 than on mouse TRPM8. A metabolite of Eucalyptol, 2-hydroxy-1,8-cineol, also activated human TRPM8. Conclusion and Implications Among the pharmacological targets of Eucalyptol TRPM8 is essential for its anti-inflammatory effects in mice. The much higher sensitivity of human TRPM8 to Eucalyptol compared to the rodent orthologues explains the higher potency of Eucalyptol in humans. Metabolites of Eucalyptol likely contribute to the anti-inflammatory effects. The development of more potent and selective TRPM8 agonists may yield novel anti-inflammatory therapeutics.
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the anti inflammatory effects of Eucalyptol in a mouse model of lps induced pulmonary inflammation are mediated by trpm8
European Respiratory Journal, 2016Co-Authors: Anabel De Caceres Bustos, Boyi Liu, Sairam V Jabba, John B Morris, Sveneric JordtAbstract:Eucalyptol (1,8-cineol) has long been known for its anti-inflammatory properties. It interacts with Transient Receptor Potential (TRP) ion channels among other targets, but it is unclear which of these mediates its anti-inflammatory effects. In this work, the effects of Eucalyptol were compared in WT and TRPM8-deficient mice in a model of pulmonary inflammation following intranasal administration of lipopolysaccharide (LPS). LPS, a component of Gram-negative bacterial cell walls, plays a major role in acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). 24 hours after LPS intranasal instillation, lungs and bronchoalvelolar lavage (BAL) from Eucalyptol treated and untreated TRPM8 KO and WT mice were collected and analyzed. This study shows that Eucalyptol treatment diminishes leukocyte infiltration, myeloperoxidase activity and cytokine production in the lung. Genetic deletion of TRPM8 abolishes the anti-inflammatory effects of Eucalyptol in the LPS model. Eucalyptol is at least 30-fold more potent on human TRPM8 than on mouse TRPM8, and a metabolite of Eucalyptol, 2-hydroxy-1,8-cineol, also activates human TRPM8. Our data show that among the pharmacological targets of Eucalyptol, TRPM8 is essential for its anti-inflammatory effects.The development of more potent and selective TRPM8 agonists may yield novel anti-inflammatory pharmacological treatments with lower toxicity and adverse effects than the current available options.
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trpm8 mediates the anti inflammatory effects of Eucalyptol in a mouse model of lps induced pulmonary inflammation
The FASEB Journal, 2016Co-Authors: Ana Isabel Caceres, Boyi Liu, Sairam V Jabba, John B Morris, Sveneric JordtAbstract:Eucalyptol (1,8-cineol), the major ingredient in the essential oil of the eucalyptus leaves and other medicinal plants, has long been known for its anti-inflammatory properties. Eucalyptol interact...