†These authors contributed equally.
Depression is closely linked to hypothalamus-pituitary-adrenal
axis hyperactivity. Honokiol, a biphenolic lignan compound obtained from the
traditional Chinese medicine Magnolia officinalis, can reduce the activity of the
hypothalamus-pituitary-adrenal axis and improve depression-like behavior caused
by hypothalamus-pituitary-adrenal axis hyperactivity. The current study
investigated the specific mechanism of action of this effect. A depression model
was established by repeated injections of corticosterone to study the
antidepressant-like effect of honokiol and its potential mechanism. Honokiol
prevented the elevated activity of the hypothalamus-pituitary-adrenal axis and
the depression-like behavior induced by corticosterone. Treatment with honokiol
resulted in greater glucocorticoid receptor mRNA expression, greater
glucocorticoid receptor-positive expression, and a greater ratio of
glucocorticoid receptor to the mineralocorticoid receptor in the hippocampus.
Moreover, honokiol treatment led to lower levels of interleukin-1