title: Borneol Is a TRPM8 Agonist that Increases Ocular Surface Wetness.
abstract: Borneol is a compound widely used in ophthalmic preparations in China. Little is known about its exact role in treating eye diseases. Here we report that transient receptor potential melastatin 8 (TRPM8) channel is a pharmacological target of borneol and mediates its therapeutic effect in the eyes. Ca2+ measurement and electrophysiological recordings revealed that borneol activated TRPM8 channel in a temperature- and dose-dependent manner, which was similar to but less effective than the action of menthol, an established TRPM8 agonist. Borneol significantly increased tear production in guinea pigs without evoking nociceptive responses at 25°C, but failed to induce tear secretion at 35°C. In contrast, menthol evoked tearing response at both 25 and 35°C. TRPM8 channel blockers N-(3-Aminopropyl)-2-[(3-methylphenyl)methoxy]-N-(2-thienylmethyl)benzamide hydrochloride (AMTB) and N-(4-tert-butylphenyl)-4-(3-chloropyridin-2-yl)piperazine-1-carboxamide (BCTC) abolished borneol- and menthol-induced tear secretion. Borneol at micromolar concentrations did not affect the viability of human corneal epithelial cells. We conclude that borneol can activate the cold-sensing TRPM8 channel and modestly increase ocular surface wetness, which suggests it is an active compound in ophthalmic preparations and particularly useful in treating dry eye syndrome.
authors.affiliation: Ministry of Education Key Laboratory of Bio-resources and Eco-environment, College of Life Sciences, Sichuan University, Chengdu, China.|Key Laboratory of Medical Electrophysiology, Ministry of Education, and Institute of Cardiovascular Research, Sichuan Medical University, Luzhou, China.
authors.forename: Gui-Lan
authors.initials: GL
authors.lastname: Chen
authors.affiliation: Key Laboratory of Medical Electrophysiology, Ministry of Education, and Institute of Cardiovascular Research, Sichuan Medical University, Luzhou, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Lei
authors.affiliation: Key Laboratory of Medical Electrophysiology, Ministry of Education, and Institute of Cardiovascular Research, Sichuan Medical University, Luzhou, China.
authors.forename: Lu-Ping
authors.initials: LP
authors.lastname: Zhou
authors.affiliation: Key Laboratory of Medical Electrophysiology, Ministry of Education, and Institute of Cardiovascular Research, Sichuan Medical University, Luzhou, China.
authors.forename: Bo
authors.identifier: http://orcid.org/0000-0002-3474-3158
authors.initials: B
authors.lastname: Zeng
authors.affiliation: Ministry of Education Key Laboratory of Bio-resources and Eco-environment, College of Life Sciences, Sichuan University, Chengdu, China.
authors.forename: Fangdong
authors.initials: F
authors.lastname: Zou
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D001892:Camphanes / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D015352:Dry Eye Syndromes / Q000188:drug therapy; D055724:Electrophysiological Phenomena / Q000187:drug effects; D005123:Eye / Q000187:drug effects*; D005260:Female; D006168:Guinea Pigs; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D008610:Menthol / Q000494:pharmacology; D059226:Nociceptive Pain; D013501:Surface-Active Agents / Q000494:pharmacology*; D050053:TRPM Cation Channels / Q000819:agonists*; D013666:Tears / Q000187:drug effects
chemical_list: D001892:Camphanes; D013501:Surface-Active Agents; D050053:TRPM Cation Channels; D008610:Menthol; C022871:isoborneol; D002118:Calcium