## 1 Introduction  
During menopause, low estrogen levels can lead to various health problems such as hot flashes, sleep issues, joint pain, circulation disorder, bone loss, and depression [1, 2]. Estrogen is considered to benefit various organs such as the heart, brain, blood, and uterus, as well as bone resorption via reduction in osteocl activity or production of osteoblastic activity [1, 2]. Estrogen also plays an important role in the serotonergic system, where it balances mood through regulation [3]. Estrogen regulates bone formation, maturity, and metabolism in both women and men [4, 5, 6]. In menopause, a low estrogen level leads to increased modification rates due to an imbalance between bone resorption by osteoclasts and osteogenesis by osteoblasts [6]. This condition is linked with decreased BMD, which leads to an increased risk of fracture. Aromatase deficiency (owing to mutations in the cytochrome P450 subfamily 19 (CYP19) gene) leads to lessened BMD, delayed epiphysis, and decreased patient height. Bone loss was also experimentally noted in aromatase knockout mice [7]. Estrogen affects dopaminergic neurotransmission through mechanisms including synthesis, release, rotation, and degradation [8]. Estrogen has potent serotonin regulatory properties at the neurotransmitter synthesis level through tryptophan hydroxylase regulation [9; 10]. Estrogen's effect on serotonin expression is also considered to modify the treatment duration in receptor subtypes, brain regions, and estrogen therapy cases [9; 10]. Estrogen administration has been linked with increased tryptophan hydroxylase transcripts such as TPH1 and TPH2 [11; 12; 13].  
_Ecklonia cava_ Kjellman (EC) is a marine-brown-colored alga found in the seaside and oceans off of Korea. It is used as a therapeutic herbal agent in the form of seanol, an extract. Its components include phloroglucinol, eckol, dieckol, 6,6\({}^{\prime}\)-biekcol, and 8,8\({}^{\prime}\)-bieckol, and other common components such as sterol derivatives [14; 15; 16]. The health benefits and chemistry of EC have been previously investigated, revealing its role in dietary supplements and treatments. Per previous studies, EC has antioxidant, anti-inflammatory, anti-diabetic, and anti-cancer properties [14; 15; 16; 17]. EC has long been one of the ingredients used in many foods in Korea. EC has other benefits such as promoting hair growth through topical application and prevention of hair loss due to androgen [15].  
In our previous study, EC and its ingredients of eckol, dieckol, 6,6\({}^{\prime}\)-dieckol, 8,8\({}^{\prime}\)-dieckol, and phloroglucinol were quantified using UHPLC-Triple-Q-MS/MS. Furthermore, EC was found to regulate hormonal disturbance among women with ovarian disease that induces estrogen deficiency through aromatase inhibition in the rodent model. EC effectively prevented the creation of dyndroepiandrosetore and its monitoring led to reduction in the blood androgen level, resulting in the alleviation of ovarian failure symptoms. However, as a consequence of confirming the expression in the pS2 gene used as an estrogen-active transcript marker, no estrogen-like effect was noted [18].  
Recently, the efficacy of EC therapy on various menopause symptoms was studied in ovariectomized and restraint-stressed mice. Ovariectomy is a commonly used model to investigate menopausal symptoms due to the lack of ovarian hormones such as estrogen and progesterone. In the present study, a mouse model of ovariectomy and restraint stress was used to determine whether EC improves the serum lipid profile, bone loss, and depression in the menopausal mouse model. To add insight into the interaction of EC with bone metabolism and/or the serotonergic system through ALP, CTX, osteogeniccin, PINP, TPHs, and 5-HT activities, reuptake was studied in in vitro and in vivo models. This mouse model was also used to study whether EC balances serum serotonin level and immobility time in a restraint-stressed mouse model.