Aqueous extract of lily bulb ameliorates menopause-like behavior in ovariectomized mice with novel brain-uterus mechanisms distinct from estrogen therapy

Abstract Background Lily bulb is often used as a dietary supplement for menopause. This study was aimed to investigate the ameliorative effects of aqueous extract of lily bulb (AELB) on the menopause-associated psychiatric disorders and the underlying mechanisms in comparison with estrogen therapy. Methods Ovariectomized (OVX) mice were treated with 1.8 g/kg AELB or 0.3 mg/kg estradiol for 5 weeks. Animals were tested in multiple behavioral paradigms. Serum, uterus, and brain tissues were collected for the measurement of neurotransmitters and their related biomarkers, neurotrophins, and estrogen receptor α (ERα) and β (ERβ). Results AELB and estradiol had similar anxiolytic, antidepressant, and cognition-improving effects. While estradiol limited OVX-induced weight gains and prevented uterine shrinkage and the drop of serum estrogen level, AELB had minor and even no effects on these indices. AELB, but not estradiol, reversed OVX-induced decreases in the expression levels of hippocampal nerve growth factor (NGF) and prefrontal glial cell-derived neurotrophic factor (GDNF). In addition to hypothalamic and prefrontal ERα, AELB enhanced uterine and brain regional ERβ expression levels without affecting uterine ERα, NGF, and GDNF. Conversely, estradiol completely restored the expression levels of estrogen receptors and neurotrophins in uterus. Conclusions While AELB is comparable to estradiol in alleviating menopause-like behavior, it has distinct brain-uterus mechanisms in association with the predominant protection of catecholamine synthesis, neurotrophins, and ERβ receptors in brain, but with minor effects on uterus. AELB and its constituents may be novel treatments for menopause.