Liquiritin,a novel inhibitor of TRPV1 and TRPA1, protects against LPS-induced acute lung injury |
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| Institution: | 1. Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China;2. School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China;3. Department of Integrative Biology and Pharmacology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA;4. The Brain Science Center, Beijing Institute of Basic Medical Sciences, Beijing 100850, China;1. Institute of Physiology and Pathophysiology, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany;2. Center of Physiology and Pharmacology Medical University of Vienna, Vienna, Austria;1. School of Life Sciences and Technology, Xinxiang Medical University, Xinxiang 453003, Henan, China;2. School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang 453003, Henan, China;3. Disciplinary Group of Psychology and Neuroscience, Xinxiang Medical University, Xinxiang 453003, Henan, China;4. Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine in Henan Province, Xinxiang Medical University, Xinxiang 453003, Henan, China;1. Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University Graduate School of Medical Sciences, Aichi, Japan;2. Department of Anatomy and Neuroscience, Nagoya City University Graduate School of Medical Sciences, Aichi, Japan;1. School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China;2. Auckland Bioengineering Institute, University of Auckland, New Zealand;3. School of Health Sciences, Caritas Institute of Higher Education, Tseung Kwan O, Hong Kong SAR, China;1. Department of Cardiology, Huaihe Hospital, Henan University, Kaifeng 475000, China;2. Department of Cardiology, The Fifth people’s Hospital of Shenzhen City, Shenzhen 518001, China;1. Vital Beautie Research Institute, Amorepacific Corporation R&D Center, Yongin, Republic of Korea;2. Medical Beauty QA Team, Aestura Corporation, Anseong, Republic of Korea |
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| Abstract: | TRPV1 and TRPA1 are cation channels that play key roles in inflammatory signaling pathways. They are co-expressed on airway C-fibers, where they exert synergistic effects on causing inflammation and cough. Licorice, the root of Glycyrrhiza uralensis, has been widely used in China as an anti-inflammatory and anti-coughing herb. To learn if TRPV1 and TRPA1 might be key targets of the anti-inflammatory and antitussive effects of licorice, we examined liquiritin, the main flavonoid compound and active ingredient of licorice, on agonist-evoked TRPV1 and TRPA1 activation. Liquiritin inhibited capsaicin- and allyl isothiocyanate-evoked TRPV1 and TRPA1 whole-cell currents, respectively, with a similar potency and maximal inhibition. In a mouse acute lung injury (ALI) model induced by the bacterial endotoxin lipopolysaccharide, which involves both TRPV1 and TRPA1, an oral gavage of liquiritin prevented tissue damage and suppressed inflammation and the activation of NF-κB signaling pathway in the lung tissue. Liquiritin also suppressed LPS-induced increase in TRPV1 and TRPA1 protein expression in the lung tissue, as well as TRPV1 and TRPA1 mRNA levels in cells contained in mouse bronchoalveolar lavage fluid. In cultured THP-1 monocytes, liguiritin, or TRPV1 and TRPA1 antagonists capsazepine and HC030031, respectively, diminished not only cytokine-induced upregulation of NF-κB function but also TRPV1 and TRPA1 expression at both protein and mRNA levels. We conclude that the anti-inflammatory and antitussive effects of liquiritin are mediated by the dual inhibition of TRPV1 and TRPA1 channels, which are upregulated in nonneuronal cells through the NF-κB pathway during airway inflammation via a positive feedback mechanism. |
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| Keywords: | Liquiritin TRPV1 TRPA1 ALI LPS Inflammation |
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