Search Results (99)

Background/Objectives: Estrogen deficiency contributes to dyslipidemia and visceral adiposity, increasing cardiovascular risk in postmenopausal women. Sargassum fulvellum (Sf), a brown seaweed rich in bioactive compounds, possesses lipid-regulating properties that may be enhanced by lactic acid bacteria fermentation. This study aimed to evaluate the effects of fermented S. fulvellum (SfLlLm), prepared using Lactococcus lactis and Leuconostoc mesenteroides, on lipid metabolism and adipose tissue remodeling in an ovariectomized (OVX) mouse model of estrogen deficiency. Methods: Female C57BL/6 mice underwent ovariectomy and were fed an AIN-76A diet supplemented with either unfermented Sf or SfLlLm for eight weeks. Sham-operated and 17β-estradiol-treated OVX groups served as controls. Serum lipid levels—total cholesterol, triglycerides, LDL-C, and HDL-C—were assessed, and histological analysis of visceral adipose tissue was conducted to evaluate adipocyte morphology. Results: OVX-induced estrogen deficiency led to increased total cholesterol, triglycerides, and LDL-C, along with hypertrophic changes in visceral adipocytes. Supplementation with fermented Sargassum fulvellum (SfLlLm) markedly improved these parameters, reducing total cholesterol by 6.7%, triglycerides by 9.3%, and LDL-C by 52.9%, while increasing HDL-C by 17.5% compared to the OVX controls. SfLlLm also normalized visceral adipocyte size and distribution. These effects were comparable to or exceeded those of 17β-estradiol treatment. Conclusions: Fermented SfLlLm ameliorated dyslipidemia and visceral adiposity under estrogen-deficient conditions. These findings support its potential as a functional dietary intervention for managing postmenopausal lipid disorders and associated metabolic complications. Full article

Background/Objectives: Ovariectomized rodents experience metabolic dysfunction in whole-body and skeletal muscle. A disrupted balance between oxidative stress and antioxidants might exacerbate metabolic dysfunction in ovariectomized rodents. Dietary antioxidants, such as vitamin E intake, before or during exercise would be beneficial by mitigating the exercise-induced increase in oxidative stress in ovariectomized rodents. The purpose of the current study was to investigate the potential effect of vitamin E intake combined with voluntary exercise on whole-body and skeletal muscle metabolism in ovariectomized mice. Methods: This study used C57BL/6J wild-type female mice (n = 40, 8 weeks old), which were randomly assigned into sham (SHM), ovariectomy (OVX), ovariectomy with exercise (OVXVE), ovariectomy with vitamin E (OVXV), ovariectomy with exercise and vitamin E (OVXVE) groups. Body composition, resting metabolic rate, glucose tolerance, skeletal muscle mitochondrial function, and protein contents were assessed using dual-energy x-ray absorptiometry, indirect calorimetry, glucose tolerance test, O₂K OROBOROS, and Western blot, respectively. Results: The combined treatment of vitamin E and voluntary wheel running did not show a beneficial effect on whole-body metabolism such as fat mass, energy expenditure, and glucose tolerance. However, independent of exercise intervention, vitamin E intake enhanced mitochondrial function, Peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC1-a), and adenosine monophosphate-activated protein kinase (AMPK) levels and also reduced oxidative stress in the skeletal muscles of ovariectomized mice. Specifically, in the soleus muscle, vitamin E intake enhanced mitochondrial function and PGC1-a content (p < 0.05). In the gastrocnemius muscle, vitamin E intake enhanced PGC1-a and AMPK levels and reduced a marker of oxidative stress (p < 0.05). Conclusions: Vitamin E, as a potent antioxidant, may play a crucial role in maintaining skeletal muscle health in ovariectomized mice. More studies are necessary to investigate whether this finding is applicable to women. Full article

Background: Estrogen depletion alters bone mineralization and oxidative stress. Antioxidants like humic acids (HA) may help mitigate bone demineralization and redox imbalances. Thus, this study evaluated the effects of HA on bone mineral composition and oxidative stress markers in an experimental menopause model. Methods: Twenty-four female C57BL/6 mice were divided into four groups (n = 6/group): Sham; Sham + HA; Ovariectomized (OVX); and OVX + HA. The menopause model was induced by bilateral ovariectomy at the beginning of the experiment. HA derived from biomass vermicompost was administered daily by gavage for 28 days. After euthanasia, femurs and fragments of the gastrocnemius muscle, liver, and kidney were collected. Bone elemental composition was analyzed using scanning electron microscopy (SEM) coupled with energy dispersive spectroscopy (EDS). Superoxide dismutase (SOD), catalase (CAT), and hydrogen peroxide (H₂O₂) activities were assessed in muscle, renal, and hepatic tissues. Data were analyzed using two-way ANOVA and Bonferroni’s post hoc test. Results: Untreated OVX mice exhibited a significant reduction in femoral calcium content (p < 0.05). However, HA treatment increased calcium levels and improved the Ca/P ratio (p < 0.05). H₂O₂ activity was reduced in the liver and kidney of OVX + HA mice compared to untreated animals (p < 0.05). CAT activity in muscle increased in the OVX + HA group compared to the OVX (p < 0.05). Conclusions: HA treatment improved femoral elemental composition and modulated oxidative stress markers in an experimental menopause model. Full article

Background/Objectives: Menopause induces substantial metabolic changes, including a reduction in metabolic rate and an elevated risk of developing metabolic diseases. Fish oil (FO) supplementation has been shown to ameliorate menopause-associated metabolic risks. Hyperthermia treatment (HT) has recently gained attention for its potential to improve metabolic and immune health. However, it remains to be determined whether HT can confer metabolic benefits comparable to those of FO supplementation or enhance the metabolic benefits of FO supplementation. This study aims to delineate the distinctive and collaborative effects of HT and FO supplementation in mitigating menopause-associated metabolic dysfunction. Methods: Female C57BL/6 ovariectomized (OVX) mice were randomly assigned to four groups (n = 12/group) to evaluate the individual and combined effects of FO supplementation (5% w/w) and HT treatment. For HT, whole-body heat exposure was conducted at 40–41 °C for 30 min, 5 days per week. After 12 weeks, animals were used to evaluate the changes in glucose and lipid metabolism, obesity outcome, and inflammatory markers. The gut microbiome analysis was conducted from cecal content by 16S rRNA sequencing. Acute inflammation was induced by lipopolysaccharide (LPS) injection to evaluate inflammatory responses. Results: HT alone distinctively reduced weight gain, lowered core body temperature, and attenuated insulin resistance comparable to FO supplement in OVX mice. The collaborative effect of FO and HT was not evident in metabolic parameters but more prominent in attenuating proinflammatory responses and microbiota modulation. Conclusions: Our findings suggest that the combined treatment of FO supplementation and HT may serve as an effective strategy to mitigate menopause-associated immune susceptibility and metabolic dysfunction. These benefits are likely mediated, at least in part, through the reduction in inflammation and modulation of the gut microbiota. Full article

Progestogens’ anti-anxiety and anti-depressive effects and mechanisms are not well-understood. Progestogens are hypothesized to have anti-anxiety and anti-depressive effects on behavior, independent of actions at nuclear progestin receptors (NPRs) and dependent on allopregnanolone (5α-pregnan-3α-ol-20-one; 3α,5α-THP), a 5α-reduced, neuroactive metabolite of progesterone (P₄). Adult c57 mice in behavioral estrus (proestrus; pro) showed more anti-anxiety-like and anti-depressant-like behavior and higher levels of estradiol (E₂), P₄, and allopregnanolone in the hippocampus/amygdala complex. Proestrus c57 > 5α-reductase knockout (5αRKO) mice made more central entries in an open field than diestrus c57 and 5αRKO mice that were not different. Ovariectomized (OVX) c57 mice administered 1, 2, or 4 mg/kg P₄ SC showed dosage-dependent increases in central entries in an open field (more anti-anxiety-like behavior); 5αRKO mice had maximal increases at 1–2 mg/kg P₄. OVX c57 and 5αRKO mice showed maximum increases in central entries with SC 3α,5α-THP (4 mg/kg), and c57s showed a similar maximal response to P₄ (4 mg/kg), but 5αRKOs response was half at that dosage. P₄ (4 mg/kg SC to OVX c57 or progestin receptor knockout (PRKO) mice decreased immobility (depression-like behavior) in the forced swim task. Effects of E₂ and veh were similar in both groups. Levels of 3α,5α-THP in the hippocampus/amygdala were consistent with effects on central entries in the open field. Levels of brain-derived neurotrophic factor (BDNF) in the hippocampus/amygdala were greater among E₂-primed (0.09 mg/kg, SC) vs vehicle-administered mice. In sum, adult female mice can be responsive to P₄ for anti-anxiety/anti-depressant-like behavior; such effects may be independent of NPRs but require 5α-reduction and E₂’s priming actions at BDNF in the hippocampus/amygdala complex. Full article

Postmenopausal women face increased risks of osteoporosis and cardiovascular diseases due to estrogen decline. This study investigated the effects of moderate-intensity continuous training (MICT) and high-intensity interval training (HIIT) on bone microstructure and cardiovascular risk factors in ovariectomized (OVX) mice. Results showed that both exercise regimens improved blood lipid profiles and vascular structure, reducing systolic blood pressure (−11.81% and −10.89%) and undercarboxylated osteocalcin (ucOCN) levels (−52.14% and −52.05%). However, moderate-intensity exercise was more effective in enhancing bone mineral density (+82.38% and +45.02%) and microstructure recovery. No significant correlation was found between ucOCN and cardiovascular disease risk factors, such as lipid parameters, systolic blood pressure, and vascular wall thickness. This study suggests that both exercise intensities can mitigate cardiovascular risks in OVX mice, which is independent of OCN. MICT is superior for promoting osteoporosis recovery. Full article

Background: Osteoporosis is characterized by the microstructural depletion of bone tissue and decreased bone density, leading to an increased risk of fractures. Cotoneaster wilsonii Nakai, an endemic species of the Korean Peninsula, grows wild in Ulleungdo. In this study, we aimed to investigate the effects of C. wilsonii and its components on osteoporosis. Methods and Results: The alkaline phosphatase (ALP) activity of C. wilsonii extracts and fractions was evaluated in MC3T3-E1 pre-osteoblasts, and the n-hexane fraction (CWH) showed the best properties for ALP activity. The effects of the CWH on bone formation were assessed in MC3T3-E1 cells and ovariectomized mice. Biochemical assays and histological analyses focused on the signaling activation of osteoblast differentiation and osteogenic markers, such as ALP, collagen, and osterix. The CWH significantly activated TGF-β and Wnt signaling, enhancing osteoblast differentiation and bone matrix formation. Notably, CWH treatment improved micro-CT indices, such as femoral bone density, and restored serum osteocalcin levels compared to OVX controls. Conclusions: These results highlight the potential of the C. wilsonii Nakai n-hexane fraction as a promising therapeutic agent for managing osteoporosis. Full article

Vitamin K (VitK) is a vital nutrient that is newly recognized to support bone and cardiovascular health. As a nutraceutical, VitK is produced via plant extraction and bacterial fermentation. This study examined the potential anti-inflammatory and osteogenic benefits of VitK, i.e., VitK1 (phylloquinone; PK) and VitK2 (menaquinone; MKs), derived from Sargassum fulvellum fermented by Lactococcus lactis and Leuconostoc mesenteroides (SfLlLm) using lipopolysaccharide (LPS)-induced Raw264.7, MC3T3-E1 cells, and ovariectomized (OVX) mice. MK4, MK7, and MK9, as well as PK, were effectively acquired from SfLlLm and analyzed. SfLlLm_VitK reduced levels of proinflammatory cytokine in LPS-induced Raw264.7 cells and induced an osteogenesis regulating factor in MC3T3-E1 cells. In OVX mice, SfLlLm feeding reduced plasma levels of alkaline phosphatase, phosphate, and the pro-collagen type I alpha 2 gene (pro-Col1a2) while elevating cancellous bone volume and trabecular numbers. Accordingly, SfLlLm, comprising MKs, may be a candidate for preventing and treating immune and bone diseases. Full article

Pulsatilla koreana Nakai (P. koreana) is a perennial herb traditionally used to treat malaria and fever. Although the pharmacological properties of P. koreana have been explored in various contexts, its effects on bone diseases, such as osteoporosis, remain poorly studied. In this study, we investigated the effects of water extracts of P. koreana (WEPK) on osteoclasts, which play a crucial role in bone remodeling, and an ovariectomized (OVX) mouse model, which mimics osteoporosis. Phytochemical profiling of WEPK revealed several compounds that regulate bone or fat metabolism. WEPK suppressed osteoclast differentiation by downregulating the expression of receptor activator of nuclear factor-κB ligand (RANKL), a cytokine that induces osteoclastogenesis. Additionally, WEPK directly inhibited RANKL-induced differentiation of osteoclast precursors by downregulating nuclear factor of activated T cells 1 (NFATc1), the master transcription factor for osteoclastogenesis, by modulating its upstream regulators. In vivo, oral administration of WEPK suppressed bone loss, reduced weight gain, and mitigated fat accumulation in the liver and gonadal tissues of OVX mice. Given its positive impact on bone and fat accumulation under estrogen deficiency, WEPK may serve as a promising alternative therapy for postmenopausal osteoporosis, especially when accompanied by other metabolic disorders, such as obesity and fatty liver. Full article

Background: Osteoporosis, a prevalent bone metabolic disease, often requires long-term drug treatments that may lead to serious side effects. Trehalose, a natural disaccharide found in various organisms, has been shown to have a promoting effect on autophagy. However, whether trehalose can improve bone mass recovery in ovariectomized rats and its underlying mechanisms remains unclear. In this study, trehalose was administered to ovariectomized rats to evaluate its therapeutic potential for osteoporosis following ovariectomy. Methods: Micro-computed tomography (Micro-CT), hematoxylin and eosin (HE) and immunohistochemical staining techniques were utilized to evaluate the impact of trehalose on osteoporosis induced by ovariectomy (OVX) in mice, both in imaging and histological dimensions. Furthermore, the influence of trehalose on osteoblastogenesis and functional activity was quantified through Alizarin Red S (ARS) staining and immunoblotting assays. Results: Trehalose effectively mitigated bone loss, elevated autophagy and suppressed pyroptosis in ovariectomized rats. Furthermore, 3-methyladenine diminished the protective effects of trehalose, particularly in promoting autophagy and inhibiting pyroptosis. Conclusions: Trehalose demonstrates significant potential in treating osteoporosis by suppressing NLRP3 inflammasome-driven pyroptosis, primarily through autophagy promotion. This suggests that trehalose could be a promising, safer alternative treatment for osteoporosis. Full article

Background: Sarcopenia, characterized by muscle mass decline due to aging or other causes, is exacerbated by decreased estrogen levels after menopause in women. Isoflavones, a class of flavonoids acting on estrogen receptors, may have beneficial effects on metabolic disorders. We examined these effects in ovariectomized mice fed a high-fat, high-sucrose diet (HFHSD). Methods: At 7 weeks old, female C57BL6/J mice (18–20 g, n = 12) underwent bilateral ovariectomy (OVX), and were then fed a high-fat, high-sucrose diet starting at 8 weeks of age. Half of the mice received isoflavone water (0.1%). Metabolic analyses, including glucose and insulin tolerance tests, were conducted. Muscle analysis involved grip strength assays, next-generation sequencing, quantitative RT–PCR, and western blotting of skeletal muscle after euthanizing the mice at 14 weeks old. Additionally, 16S rRNA gene sequence analysis of the gut microbiota was performed. Results: The results demonstrated that isoflavone administration did not affect body weight, glucose tolerance, or lipid metabolism. In contrast, isoflavone-treated mice had higher grip strength. Gene expression analysis of the soleus muscle revealed decreased Trim63 expression, and western blotting showed inactivation of muscle-specific RING finger protein 1 in isoflavone-treated mice. Gut microbiota analysis indicated higher Bacteroidetes and lower Firmicutes abundance in the isoflavone group, along with increased microbiota diversity. Gene sets related to TNF-α signaling via NF-κB and unfolded protein response were negatively associated with isoflavones. Conclusions: Isoflavone intake alters gut microbiota and increases muscle strength, suggesting a potential role in improving sarcopenia in menopausal women. Full article

Postmenopausal women have a higher probability of experiencing cognitive alterations compared to men, suggesting that the decline in female hormones may contribute to cognitive deterioration. Thailand traditionally uses Tri-Kaysorn-Mas (TKM), a blend of three medicinal herbs, as a tonic to stimulate appetite and relieve dyspepsia. Due to its antioxidant and anti-acetylcholinesterase activities, we investigated the effects of TKM (50 and 100 mg/kg/day, p.o., for 8 weeks) on cognitive deficits and their underlying causes in an ovariectomized (OVX) mouse model of menopause. OVX mice showed cognitive impairment in the Y-maze, novel object recognition task (NORT), and Morris water maze (MWM) behavioral tests, along with atrophic changes to the uterus, altered levels of serum 17β-estradiol, and down-regulated expression of estrogen receptors (ERα and ERβ). These behavioral effects were reversed by TKM. TKM decreased malondialdehyde (MDA) levels and mitigated oxidative stress in the brain by enhancing the activity of superoxide dismutase (SOD) and catalase (CAT) and by up-regulating the antioxidant-related gene Nrf2 while down-regulating Keap1. TKM also counteracted OVX-induced neurodegeneration by enhancing the expression of the neurogenesis-related genes BDNF and CREB. The results indicate that TKM extract alleviates oxidative brain damage and neurodegeneration while enhancing cognitive behavior in OVX mice, significantly improving cognitive deficiencies related to menopause/ovariectomy through multiple targets. Full article

Rice bran, which is abundant in dietary fiber and phytochemicals, provides multiple health benefits. Nonetheless, its effects on neuroinflammation and gut microbiota in postmenopausal conditions are still not well understood. This study investigated the effects of rice bran and/or tea seed oil supplementation in d-galactose-injected ovariectomized (OVX) old mice fed a fructose drink. The combination of d-galactose injection, ovariectomy, and fructose drink administration creates a comprehensive model that simulates aging in females under multiple metabolic stressors, including oxidative stress, estrogen deficiency, and high-sugar diets, and allows the study of their combined impact on metabolic disorders and related diseases. Eight-week-old and 6–8-month-old female C57BL/6 mice were used. The mice were divided into six groups: a sham + young mice, a sham + old mice, an OVX + soybean oil, an OVX + soybean oil with rice bran, an OVX + tea seed oil (TO), and an OVX + TO with rice bran diet group. The OVX groups were subcutaneously injected with d-galactose (100 mg/kg/day) and received a 15% (v/v) fructose drink. The rice bran and tea seed oil supplementation formed 10% of the diet (w/w). The results showed that the rice bran with TO diet increased the number of short-chain fatty acid (SCFA)-producing Clostridia and reduced the number of endotoxin-producing Tannerellaceae, which mitigated imbalances in the gut–liver–brain axis. Rice bran supplementation reduced the relative weight of the liver, levels of hepatic triglycerides and total cholesterol; aspartate transaminase and alanine aminotransferase activity; brain levels of proinflammatory cytokines, including interleukin-1β and tumor necrosis factor-α; and plasma 8-hydroxy-2-deoxyguanosine. This study concludes that rice bran inhibits hepatic fat accumulation, which mitigates peripheral metaflammation and oxidative damage and reduces neuroinflammation in the brain. Full article

Lower urinary tract symptoms (LUTS) are common in postmenopausal women. These symptoms are often linked to decreased estrogen levels following menopause. This study investigated the relationship between estrogen levels, alterations in bladder tissue structure, bladder function, and the incidence of urinary frequency. An age-appropriate bilateral ovariectomized mouse model (OVX) was developed to simulate conditions of estrogen deficiency. Mice were divided into three groups: a sham-operated control group, OVX, and an estradiol-treated group. The assessments included estrogen level measurement, urination frequency, cystometry, histological analysis, immunofluorescence staining, and real-time quantitative PCR. Additionally, we quantified the expression of the mechanosensitive channel proteins Piezo1 and TRPV4 in mouse bladder tissues. Lower estrogen levels were linked to increased voiding episodes and structural changes in mouse bladder tissues, notably a significant increase in Collagen III fiber deposition. There was a detectable negative relationship between estrogen levels and the expression of Piezo1 and TRPV4, mechanosensitive proteins in mouse bladder tissues, which may influence voiding frequency and nocturia. Estrogen treatment could improve bladder function, decrease urination frequency, and reduce collagen deposition in the bladder tissues. This study explored the connection between estrogen levels and urinary frequency, potentially setting the stage for novel methods to address frequent urination symptoms in postmenopausal women. Full article

When postmenopausal women are under stress conditions, this exacerbates mood disorders and issues with neuroimmune systems. The porcine placenta is known to relieve menopausal depression in clinical trials, but its underlying mechanisms for depression and anti-inflammatory functions remain poorly defined. The present study was designed to examine the anti-inflammatory effects of enzymatic porcine placenta hydrolysate (EPPH) on LPS-induced levels of nitric oxide (NO), prostaglandin E2 (PGE2), corticosterone (CORT), and pro-inflammatory cytokine interleukin-1 beta (IL-1β) in RAW 264.7 macrophage cells. In addition, the neurite outgrowth of PC12 cells was evaluated to examine the effects of EPPH on neurite growth. To mimic the symptoms of women with menopause-related depression, a stressed ovariectomized (OVX) female mouse model was used to evaluate the antidepressant effects of EPPH. The female mice were randomly divided into five groups: (1) the sham-operated (Sham) group, (2) the OVX + repeated stress + saline-treated (OVX + ST) group, (3) the OVX + repeated stress + estradiol (0.2 mg/kg)-treated (positive control) group, (4) the OVX + repeated stress + EPPH (300 mg/kg)-treated (300) group, and (5) the OVX + repeated stress + EPPH (1500 mg/kg)-treated (1500) group. Female mice were OVX and repeatedly immobilization-stressed for 2 weeks (2 h/day). A tail suspension test was conducted on the 13th day, followed by the forced swimming test on the 14th day to assess the antidepressant effects of EPPH. After the behavioral tests, the levels of CORT, PGE2, and IL-1β were evaluated. In addition, c-Fos expression in the paraventricular nucleus (PVN) was evaluated using immunohistochemistry. The concentrations of NO, PGE2, and IL-1β stimulated by LPS were significantly reduced via the addition of EPPH to RAW 264.7 cells. EPPH significantly promoted neurite outgrowth in PC12 cells compared to that of the controls. In the tail suspension test, the duration of immobility was reduced in mice treated with EPPH 1500 compared to the OVX + ST group. The EPPH 1500 group had significantly decreased levels of c-Fos-positive neurons in the PVN and reduced levels of CORT and IL-1β in the serum of the Sham group. These results suggested that the high dose of EPPH administration induced the antidepressant-like effect in the ovariectomized mice with repeated stress via downregulating the levels of CORT, IL-1β, and PGE2 in the serum through reducing the expression of c-Fos in the PVN regions. Full article