Hinokitiol inhibits compound action potentials in the frog sciatic nerve

Hinokitiol (β-thujaplicin) is a natural tropolone derivative contained in Chamaecyparis taiwanensis that has various actions including anti-inflammatory activities. Various plant-derived compounds inhibit compound action potentials (CAPs) in a manner dependent on the chemical structure of the compounds; however, the effects of hinokitiol on nerve conduction have not been examined. To determine whether hinokitiol inhibits CAPs and, if so, the chemical structure of hinokitiol that is important in this inhibition, we examined the effects of hinokitiol and its related compounds on fast-conducting CAPs using the frog sciatic nerve and the air-gap method. Hinokitiol concentration-dependently reduced the peak amplitude of CAPs with a half-maximal inhibitory concentration (IC50) value of 0.54 mM. A stereoisomer of hinokitiol, γ-thujaplicin, also inhibited CAPs. Although hinokitiol has hydroxyl, carbonyl and isopropyl groups, all of which are bound to its seven-membered ring, tropolone, which lacks the isopropyl group, had no effects on CAPs. Moreover, CAPs were unaffected by kojic acid, which lacks an isopropyl group, and also by guaiazulene, which has an isopropyl group but not carbonyl or hydroxyl groups. Biosol and 4-isopropylphenol, which have isopropyl and hydroxyl groups bound to their six-membered ring, reduced CAP peak amplitudes. This 4-isopropylphenol's activity was more effective than 4-isopropylcyclohexanol and phenol, and less effective than 4-tert-butylphenol and 4-tert-amylphenol; isopropylbenzene had no effects on CAPs. These results indicate that hinokitiol inhibits frog CAPs, possibly through interaction involving its isopropyl, carbonyl and hydroxyl groups. Hinokitiol, therefore, has an ability to inhibit nerve conduction, which contributes partly to the pharmacological actions of hinokitiol.