Icariin, a
flavonoid glycoside isolated from Epimedium brevicornum, exerts a variety of
biological activities. However, its effects on depression-induced
glucocorticoid resistance in
asthma and the underlying mechanisms have not been elucidated. In this study, a murine model of
asthma with depression was established by exposure to
ovalbumin combined with chronic unpredictable mild stress, and
icariin was given orally during
ovalbumin challenge and chronic unpredictable mild stress exposure. Depression-like behaviors were assessed by the open field test, forced swim test, and tail suspension test. The characteristic features of allergic
asthma, including airway hyperreactivity, histopathology, inflammatory
cytokine levels in bronchoalveolar lavage fluid, and
immunoglobulin E and
corticosterone levels in serum, were examined. Following splenocyte isolation in vitro, the inhibitory effects of
corticosterone on the proliferation and
cytokine secretion of splenocytes,
glucocorticoid receptor DNA-binding activity, and expression of p-
glucocorticoid receptor s226,
glucocorticoid receptor α, and p-p38
mitogen-activated protein kinase in splenocytes were determined. We found that
icariin had limited effects on depression-like behaviors, however, it markedly suppressed
airway hyperresponsiveness, inflammatory infiltration in lung tissues, levels of
interleukin-4,
interleukin-5, and
interleukin-6 in bronchoalveolar lavage fluid, and
immunoglobulin E in serum. Furthermore,
icariin improved the inhibitory effects of
corticosterone on
lipopolysaccharide-stimulated splenocytes, increased the
glucocorticoid receptor expression and
glucocorticoid receptor DNA-binding activity, and inhibited the phosphorylation of
glucocorticoid receptors S226 and
p38 mitogen-activated protein kinase. Taken together,
icariin improved
glucocorticoid resistance in a murine model of
asthma with depression associated with enhancement of
glucocorticoid receptor function and
glucocorticoid receptor expression, and its effects on the
glucocorticoid receptor function were related to decreased phosphorylation of
glucocorticoid receptors S226 and
p38 mitogen-activated protein kinase.