A Modified Formulation of Sutaehwan Ameliorates Menopausal Anxiety, Depression and Heart Hypertrophy in the VCD-Induced Menopausal Mouse Model

Abstract

Sutaehwan (STH) has been used in Korean medicine for the treatment of abortus habitualis such as fetal restlessness in the uterus. Previously, we reported that a modified formulation of STH, Sutaehwan-Gami, has phytoestrogen-like properties in an ovariectomized menopausal rat model. However, the therapeutic effects of STH and the precise mechanisms by which STH affects various menopausal symptoms remain poorly understood. The current study was designed to explore the effects of a modified form of STH on menopausal anxiety, depression and heart hypertrophy and its mechanisms in 4-vinylcyclohexene diepoxide (VCD)induced menopausal mouse models. VCD-induced menopausal model mice were fed a modified form of STH, which contained water extract of 3 herbs (called STH_KP17001) at a dose of 100 or 300 mg/kg/d or as a positive control, estradiol at a dose of 0.2 mg/kg/d with standard mouse pellets for 13 weeks. The results show that STH_KP17001 significantly restored the VCD-induced weight reduction of uterine and ovary through the phosphorylation of extracellular signal-regulated kinase (ERK) and protein kinase B (AKT) in the uterus and ovary. Moreover, STH_KP17001 showed slight proliferative effects and estrogen receptor α phosphorylation in MCF-7 cells. Treatment with STH_KP17001 reversed VCD-induced anxiety and depression through AMP-activated protein kinase (AMPK) activation and brain-derived neurotrophic factor (BDNF) expression in the cerebral cortex, while improving heart hypertrophy through inactivation of inhibitor of kappaB α (IκBα) in the heart. The results indicate that STH_KP17001 improves menopause-induced anxiety, depression and heart hypertrophy, implying its protective role for the management of menopausal symptoms.

APOE4 genotype exacerbates the impact of menopause on cognition and synaptic plasticity in APOE‐TR mice

“…First, the brain neurotrophic factor BDNF, described to be multifaceted and considered a flexible hub for synaptic plasticity and cognitive functioning 78 was reduced as a result of APOE4 genotype and VCD treatment. Such observation is in agreement with previous studies focusing on APOE4 79 and VCD treatment separately 80 . Interestingly BDNF is known to influence both mTOR and ERK activation 81 .…”

“…Such observation is in agreement with previous studies focusing on APOE4 79 and VCD treatment separately. 80 Interestingly BDNF is known to influence both mTOR and ERK activation. 81 mTOR signaling was impaired by the APOE4*VCD combination.…”

Meta-analysis: Early Age at Natural Menopause and Risk for All-Cause and Cardiovascular Mortality

“…Estrogens also play a key role in the regulation of calcium homeostasis, and thus fine-tuning the normal process of cardiomyocyte contraction and relaxation [36]. Of course, it has also been suggested that this increased risk is associated with an increase in luteinizing hormone [37] or modulation of T cells [38].…”

Effects of Radix Polygalae on Cognitive Decline and Depression in Estradiol Depletion Mouse Model of Menopause

“…VCD-induced estradiol depletion, unlike OVX, undergoes progressive degeneration like the human menopausal process and residual tissues maintain their secretory function of other hormones [48]. Cognitive impairment, anxiety, and depression were observed in the VCD-induced estradiol depletion model [37,49]. Based on the literature, the optimal dose of VCD to accelerate estradiol depletion was 160 mg/kg for 20 days [47,48].…”

“…Radix Polygalae (RP) is the root of Polygala tenuifolia Willdenow and has traditionally been used as an expectorant, tranquilizer, and memory booster [34][35][36]. Recent studies have demonstrated that it may have effects on dementia prevention, neuroprotection, and antidepressant [37]. RP improved memory and increased ChAT activity in β-amyloid induced learning and memory-impaired animal models [38].…”