3,5-Dihydroxy-4-methoxybenzyl alcohol, a novel antioxidant isolated from oyster meat, inhibits the hypothalamus–pituitary–adrenal axis to regulate the stress response

Abstract

Background

Antioxidants that can scavenge reactive oxygen in the brain and inhibit hyperactivity of the HPA axis are desirable.

Aims

We investigated the cerebral translocation of the antioxidant 3,5-dihydroxy-4-methoxybenzyl alcohol (DHMBA) and the effects of DHMBA administration on the hypothalamus–pituitary–adrenal (HPA) axis in stress-loaded rats.

Methods

Experiment 1: Plasma and brain DHMBA concentrations were measured over time after oral DHMBA administration to male B6 mice. Experiment 2: Female Wistar Imamichi rats were used. The normal group was not subjected to stress. The stress, DHMBA, and vitamin E groups were subjected to individual and overcrowding stress. Brain and hippocampal 8-hydroxy-2′-deoxyguanosine levels, hippocampal glucocorticoid receptor-α levels, plasma corticosterone levels and RNA levels of glutathione peroxidase 4, catalase, and glutathione reductase in the hippocampus were measured.

Results

In Experiment 1, DHMBA was not detected in the plasma or brain before DHMBA administration but was detected in both after administration. In Experiment 2, brain and hippocampal 8-hydroxy-2′-deoxyguanosine levels and plasma corticosterone levels were significantly lower in the DHMBA than in the stress group. Glucocorticoid receptor-α levels were higher in the DHMBA than in the stress group. DHMBA increased RNA levels of antioxidant enzymes in the hippocampus. Conclusion: DHMBA was translocated to the brain after administration. DHMBA administration decreased 8-hydroxy-2′-deoxyguanosine levels in the brain and hippocampus, increased hippocampal glucocorticoid receptor-α levels, and decreased the plasma corticosterone concentration, suggesting that DHMBA inhibits hyperactivity of the HPA axis. Nrf2 pathway activity induced by DHMBA resulted in increased antioxidant enzyme levels in the hippocampus.