Effect of Pueraria mirifica and miroestrol on estrogen deficiency in ovariectomized mice

Abstract

Abstract

Introduction: Estrogens are important hormonal signals and playing a critical role in reproductive system as well as non-reproductive system including central nervous system (CNS). Decreasing of estrogen in menopause women may associate with depression and cognitive impairment. Ovariectomized (OVX) mice, the estrogen deficiency model exhibited the depressive and cognitive impairment behaviors. Estrogen plays an important role in neurogenesis and synaptic plasticity of the neuron. Brain-derived neurotrophic factor (BDNF) is also promotes neurogenesis. cAMP response-element-binding protein (CREB) is an important regulator of the transcription of the BDNF gene and reduction of CREB resulting in decrease level of BDNF. Objective: This study is interested in effects of hormone replacement therapy (HRT), 17β-estradiol (E₂) and phytoestrogen, Pueraria mirifica crude extract and miroestrol on gene expression including BDNF, CREB in OVX mice correlated with depression and cognitive impairment. Materials and methods: Three  week  old  female ICR  mice  were divided into sham and OVX groups. For OVX groups, the animals were divided into 6 groups (n = 3-6). Group 1 received only corn oil. Group 2 was administered with E₂ (10 µg/kg, i.p.). Group 3-4 were administered with Pueraria mirifica crude extract (10 and 25 mg/kg, p.o , respectively) and group 5-6 were administered with miroestrol (0.1 and 1 mg/kg, i.p. , respectively). Level of estrogen serum was determined by using   Electrochemiluminescence immunoassay. Gene expression of BDNF and CREB were determined by using Reverse transcription polymerase chain reaction (RT-PCR). Results: OVX mice showed significantly decreasing in level of estrogen serum and the expression of CREB and BDNF in hippocampus and frontal cortex.  After mice received Pueraria mirifica crude extract (10 and 25 mg/kg, p.o) and miroestrol (0.1 and 1 mg/kg, i.p.) for ten weeks, the level of estrogen serum was increased as similar as E₂. The expression of CREB and BDNF in the brain of OVX mice was increased after received Pueraria mirifica crude extract and miroestrol.  Conclusion: The finding support that  Pueraria mirifica crude extract and miroestrol are good phytoestrogen   to increase level of estrogen and gene related to neurogenesis which might be improve depression and cognitive impairment.