Abstract

Ecklonia cava (EC) is a natural material commonly used to decrease swelling, allergy, cancer, and sleep issues. Using EC has been reported to regulate hormones during ovarian failure in an aromatase inhibition rodent model. The aim of this study was to investigate EC’s benefits on ovariectomized female mice. Hormone replacement therapy is beneficial in menopause, but the risk of side effects increases. In the present study, alkaline phosphatase (ALP) activity and tryptophan hydroxylases (TPHs) expression were studied after the EC extracts were incorporated as elemental, phloroglucinol, eckol, dieckol, 6,6′-biekcol, and 8,8′-bieckol. In this in vivo study, the following seven groups of 10-week-old Balb/c female mice were evaluated over 8 weeks: normal mice (Sham), ovariectomized mice (OVX), ovariectomized and restraint stressed mice (OVX + R), ovariectomized and 17β-estradiol-treated mice (OVX + R + E2), ovariectomized and fluoxetine-treated mice (OVX + R + E2), and ovariectomized and EC-extract-treated mice (OVX + R + EC150 or OVX + R + EC300). The serum lipid profile, bone loss, and depressive symptoms were investigated in an ovariectomized and restraint-stressed mice model. In the in vitro models, ALP activity was dose-dependently upregulated by EC, including phloroglucinol, eckol, dieckol, 6,6′-biekcol, and 8,8′-bieckol, in RBL-2H3 cells. The transcripts of TPH1 and TPH2 were induced by EC and/or its elements (phloroglucinol, eckol, dieckol, 6,6′-biekcol, and 8,8′-bieckol) in RBL-2H3 cells. The re-uptake activity of serotonin (5-HT) was also decreased by EC and its ingredients such as phloroglucinol, eckol, dieckol, 6,6′-biekcol, and 8,8′-bieckol. In the models, the serum cholesterol and triglyceride levels were downregulated in OVX + R mice by EC treatment. The bone mineral density (BMD) was determined in EC-treated groups, and the bone metabolism markers, CTX and osteocalcin, were also reduced to normal levels. The depression experiments revealed that the immobility time was shortened in the forced-swimming test in OVX + R mice. Moreover, the serum serotonin level was promoted by EC treatment in OVX + R mice. These results showed that EC extract inhibits bone loss and depressive symptoms in a menopausal mouse model by modulating bone metabolism markers (CTX and osteocalcin) and serotonin level in OVX + R mice.

Highlights

  • These results showed that Ecklonia cava Kjellman (EC) extract inhibits bone loss and depressive symptoms in a menopausal mouse model by modulating bone metabolism markers (CTX and osteocalcin) and serotonin level in OVX + R mice

  • All experimental groups included in the ovariectomy animal model showed significant weight gain compared with vehicle groups, but high-concentration treatment groups showed significant weight loss compared with ovariectomy groups

  • Group (32.95 ± 7.14 mg) and a similar uterine weight as the vehicle group was recorded for the OR + E2 group (139.11 ± 31.18 mg)

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Summary

Introduction

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]. 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. Estrogen has potent serotonin regulatory properties at the neurotransmitter synthesis level through tryptophan hydroxylase regulation [9,10]. Estrogen’s effect on serotonin expression is considered to modify the treatment duration in receptor subtypes, brain regions, and estrogen therapy cases [9,10]

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