Methysticin triggers the most profound inducing effect on CYP1A1. Methysticin is able to activate the AhR signaling pathway. Hepa1c1c7 cells are treated with various concentrations of kava extract (0-50 μg/mL) and six kavalactones (0-100 μM) for 24 h. The results indicate that kava extract at concentrations up to 50 μg/mL and kavalactones up to 100 μM do not induce cell death. For the following studies, kava extract at 0.78-6.25 μg/mL and kavalactones at 0.78-25 μM, concentrations that cause no damage to cells, are used [1].

Methysticin (6 mg/kg) is administered once a week for a period of 6 months to 6-month-old transgenic APP/Psen1 mice by oral gavage. Methysticin treatment activates the Nrf2 pathway in the hippocampus and cortex of mice. The Aβ deposition in brains of Methysticin-treated APP/Psen1 mice is not altered compared to untreated mice. However, Methysticin treatment significantly reduces microgliosis, astrogliosis, and secretion of the pro-inflammatory cytokines TNF-α and IL-17A. Methysticin treatment results in significant activation of the Nrf2/ARE pathway in the hippocampus and the cortex but not in the midbrain and cerebellum of ARE-luciferase reporter gene mice. Methysticin treatment significantly increases the expression of both genes compared to untreated animals [2].