Total Polysaccharides of Lily Bulb Ameliorate Menopause-Like Behavior in Ovariectomized Mice: Multiple Mechanisms Distinct from Estrogen Therapy.

Xi-Dan Zhou,Rakesh Sharma,Yu Zheng,Zhang-Jin Zhang

doi:10.1155/2019/6869350

Xi-Dan Zhou, Rakesh Sharma + Show 2 more

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https://doi.org/10.1155/2019/6869350

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Abstract

Our previous study has demonstrated the effects of aqueous extract of lily bulb in alleviating menopause-related psychiatric symptoms in ovariectomized (OVX) mice. This study sought to further investigate the psychotropic effects of total polysaccharides of lily bulb (TPLB) against anxiety, depression, and cognitive deterioration and the underlying mechanisms in OVX mice using behavioral, neurochemical, molecular, and proteomic approaches in comparison with estrogen therapy. While TPLB and estradiol showed similar effects in reducing OVX-induced anxiety, depression, and cognitive impairment, the psychotropic effects of TPLB were more closely associated with the predominant activation of estrogen receptors (ERs) and regulation of brain regional neurotransmitters and neurotrophins with minor effects on the uterus. Estradiol had similar potencies in binding affinity at ERα and ERβ, which caused widespread genetic and epigenetic effects. In contrast, TPLB displayed a higher affinity at ERβ than ERα, triggering the specific Ras/Akt/ERK/CREB signaling pathway without affecting any epigenetic activity. TPLB additionally modulated multiple proteins associated with mitochondrial oxidative stress, but estradiol did not. These results indicate that TPLB has comparable efficacy in reducing menopause-associated neuropsychological symptoms with a better safety profile compared to estrogen therapy. We suggest that TPLB could serve as a novel agent for menopause syndrome.

Highlights

Menopause, a natural physiological process for women, refers to a series of dysfunctions in the autonomic nervous system due to hormone fluctuation induced by ovarian failure, accompanied with neuropsychological symptoms, such as anxiety, depression, and cognitive deterioration [1, 2]
This study showed that the exposure of OVX mice to chronic stress caused various aberrant behaviors indicative of anxiety, depression, and cognitive deterioration in multiple behavioral test paradigms
Consistent with our previous study [8], this study revealed that total polysaccharides of lily bulb (TPLB) and estradiol almost completely reversed these aberrant behaviors, indicating the comparable efficacy of both agents in improving menopause-related psychiatric symptoms

Summary

Introduction

A natural physiological process for women, refers to a series of dysfunctions in the autonomic nervous system due to hormone fluctuation induced by ovarian failure, accompanied with neuropsychological symptoms, such as anxiety, depression, and cognitive deterioration [1, 2] These psychological disorders have a negative impact on the quality of life of menopausal women in varying degrees especially taking the increased life expectancy into consideration [3]. We hypothesized that total polysaccharides of lily bulb (TPLB) may exert the ameliorative effects on menopause-associated psychiatric symptoms To test this hypothesis, we investigated the effects of TPLB behavioral, neurochemical, molecular, and proteomic approaches and explored the underlying mechanisms associated with neurotransmitters, neurotrophins, and estrogen receptors (ERs)

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