Lignan from thyme possesses inhibitory effect on ASIC3 channel current

Area of Science:

• Natural Product Chemistry
• Neuropharmacology
• Molecular Biology

Background:

• Acid-sensing ion channels (ASICs) play crucial roles in pain and inflammation.
• Thymus armeniacus (Armenian thyme) is traditionally used for its analgesic and anti-inflammatory properties.

Purpose of the Study:

• To identify and characterize novel compounds from Thymus armeniacus with potential therapeutic applications.
• To investigate the inhibitory effects of a novel compound on ASIC channels, particularly ASIC3.
• To elucidate the chemical structure and evaluate the in vivo efficacy of the identified compound.

Main Methods:

• Acidic extraction of Thymus armeniacus and isolation of a novel compound, sevanol.
• Electrophysiological recordings of human ASIC3 and ASIC1a channels expressed in Xenopus laevis oocytes.
• Nuclear Magnetic Resonance (NMR) spectroscopy and Liquid Chromatography-Mass Spectrometry (LC-ESI(+)-MS) for structural elucidation.
• In vivo studies including thermal hyperalgesia and writhing tests in animal models.

Main Results:

• Sevanol, a novel lignan, was isolated and its structure elucidated.
• Sevanol demonstrated reversible inhibition of both transient and sustained currents of human ASIC3 channels (IC50 values of 353 ± 23 μM and 234 ± 53 μM, respectively).
• Sevanol showed significantly lower affinity for ASIC1a channels and did not affect other ASIC subtypes.
• In vivo, sevanol reversed thermal hyperalgesia and reduced acid-induced writhing responses.

Conclusions:

• Sevanol is the first identified low molecular weight natural compound with reversible inhibitory effects on human ASIC3 channels.
• The findings suggest sevanol's potential role in the analgesic and anti-inflammatory properties attributed to thyme.
• Sevanol represents a promising lead compound for developing new pain and inflammation therapeutics.