Journal of Physiology & Pathology in Korean Medicine
/
v.26
no.3
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pp.320-324
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2012
Osteoporosis is an important public health issue in postmenopausal women. It is a major public health concern and is widely believed that osteoporosis results from imbalance between bone resorption and bone formation. Recently natural products from plants have been extensively studied as therapeutic drugs to treat and prevent various diseases. Hoelen (scientific name, Poria cocos) is a mushroom that is used in traditional Chinese medicine. Hoelen exhibits anti-inflammatory activity and has a protective effect on tumor progression. However, the effect of hoelen in osteoclast differentiation remains unknown. Thus, we examined the effect of hoelen in receptor activator of nuclear factor-${\kappa}B$ ligand (RANKL)-induced osteoclast differentiation. Hoelen significantly inhibited RANKL-induced osteoclast differentiation in bone marrow-derived macrophages (BMMs) in dose dependent manner without toxicity. Also, we showed that hoelen significantly inhibited the mRNA expression of tartrate-resistant acid phophatase (TRAP) and nuclear factor of activated T cells 1 (NFATc1) in BMMs treated with RANKL. In Particular, hoelen greatly inhibited the protein expression of NFATc1. Ectopic expression of NFATc1 partially reverses hoelen-mediated inhibition of osteoclast differentiation. Taken together, our results demonstrated that hoelen may be useful treatment option of bone-related disease such as osteoporosis, reumatoid arthritis, and periodontitis.
Journal of the Korean Society of Food Science and Nutrition
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v.43
no.1
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pp.24-29
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2014
The effects of Lycii fructus and Lycii folium on osteoporosis and serum cholesterol levels were tested in ovariectomized (OVX) rats. Twenty-four female Sprague-Dawley rats were divided into four groups: Sham group (sham-operated), Control group (OVX, ovariectomized model), LCF group (Ovx+Lycii fructus extract), and LCL group (OVX+Lycium folium extract). After 8 weeks, the OVX ($330{\pm}5.39$ g), LCF ($315{\pm}2.99$ g), and LCL ($318{\pm}2.06$ g) groups showed increased body weight compared with sham group ($281{\pm}1.71$ g). The levels of serum osteocalcin (OC) also increased in the LCF ($444.6{\pm}26.9$ ng/mL) and LCL ($407{\pm}18.9$ ng/mL) groups compared with the OVX group ($107{\pm}3.52$ ng/mL). The activities of serum alkaline phosphatase (ALP) increased in the LCF ($108{\pm}2.7$ U/L) and LCL ($407{\pm}18.9$ ng/mL) groups compared with the OVX group ($95{\pm}2.9$ U/L). Stereomicroscopy found that the low bone density that developed in the OVX group was significantly reversed in the LCF and LCL groups after 8 weeks. We also obtained molecular-based in vivo evidence that supports a mechanism of action involving novel estrogen receptor ($ER{\alpha}$) modulator in the uterus. We found that expression of ER${\alpha}$ mRNA in the OVX rat uterus was elevated by Lycium chinense. These results suggest that Lycii fructus and Lycii folium administered to rats during 8 weeks after oophorectomy may partially recover postmenopausal osteoporosis or delay the progression of osteoporotic changes.
Sui, Bing-Dong;Chen, Ji;Zhang, Xin-Yi;He, Tao;Zhao, Pan;Zheng, Chen-Xi;Li, Meng;Hu, Cheng-Hu;Jin, Yan
Experimental and Molecular Medicine
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v.50
no.12
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pp.12.1-12.14
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2018
Osteoporosis develops with high prevalence in both postmenopausal women and hypogonadal men. Osteoporosis results in significant morbidity, but no cure has been established. Mesenchymal stem cells (MSCs) critically contribute to bone homeostasis and possess potent immunomodulatory/anti-inflammatory capability. Here, we investigated the therapeutic efficacy of using an infusion of MSCs to treat sex hormone-deficient bone loss and its underlying mechanisms. In particular, we compared the impacts of MSC cytotherapy in the two genders with the aim of examining potential gender differences. Using the gonadectomy (GNX) model, we confirmed that the osteoporotic phenotypes were substantially consistent between female and male mice. Importantly, systemic MSC transplantation (MSCT) not only rescued trabecular bone loss in GNX mice but also restored cortical bone mass and bone quality. Unexpectedly, no differences were detected between the genders. Furthermore, MSCT demonstrated an equal efficiency in rectifying the bone remodeling balance in both genders of GNX animals, as proven by the comparable recovery of bone formation and parallel normalization of bone resorption. Mechanistically, using green fluorescent protein (GFP)-based cell-tracing, we demonstrated rapid engraftment but poor inhabitation of donor MSCs in the GNX recipient bone marrow of each gender. Alternatively, MSCT uniformly reduced the $CD3^+T$-cell population and suppressed the serum levels of inflammatory cytokines in reversing female and male GNX osteoporosis, which was attributed to the ability of the MSC to induce T-cell apoptosis. Immunosuppression in the microenvironment eventually led to functional recovery of endogenous MSCs, which resulted in restored osteogenesis and normalized behavior to modulate osteoclastogenesis. Collectively, these data revealed recipient sexually monomorphic responses to MSC therapy in gonadal steroid deficiency-induced osteoporosis via immunosuppression/anti-inflammation and resident stem cell recovery.
Ma Jin Yrul;Lee Joung Woon;Kim Dong-Hyun;Lee Young Chul;Na Hye Sook;Zee Ok Pyo
YAKHAK HOEJI
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v.49
no.6
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pp.495-504
/
2005
In our study, osteoporosis was induced by ovariectomized in female Sprague-Daweley rats, and the prevention and treatment efficacy of the climacteric disease the postmenopausal Type I pattern was examined by using the experimental substance soybeans and arrowroot. After ovariectomy; the amount of estrogen was found to be reduced by 21.37$\%$ and it showed the tendency to be increased by 4.49$\%$ in T1 (extraction of soybeans group) and 7.62$\%$ in T2 (extraction of ferment soybeans group). The change of bone density, 14 weeks after ovariectomy in the femur, was decreased by 9.33$\%$ in N.C. group, and 5.46$\%$ in T3 (extraction of ferment arrowroot group). As pathological findings, the trabeculae of femur were detected to be abundant as normal and the frequency of the appearance of osteoclasts was very minimal. In the T3, the frequency of the appearance of the trabeculae of femur was increased to the level that could be distinguished. In regard to the accumulation of lipid in the bone marrow, the accumulation of lipid in the bone marrow was low as normal. However, in T3, the decrease to the level that could be distinguished was detected. In addition, in regard to the pathological findings of the uterus, normal uterine tissue findings were detected. In the T3, the minimal atrophy findings were detected. In conclusion, when the T3 was orally administered continuously for 14 weeks, it was thought that a certain proportion of the hormonal balance was maintained that functioned as a substance interfering the accumulation of fat, and it was considered to be of help in the treatment of not only osteoporosis Type I, but also for the prevention and treatment of various endocrinal diseases.
In this study we investigated the effects of supplementation with fucoidan from brown alga on the function of natural-killer (NK) cells to evaluate the possibility as an immunomodulator in ovariectomized (OVX) rats. A total of 18 female Wistar rats (six weeks) were used this study and 12 rats were OVX, and the rest of rats were sham-operated. The sham and one OVX group were fed standard diet, and the remaining OVX group received fucoidan (0.05% supplemented diet). After 12 weeks of supplementation, rats were sacrificed to assess the tumoricidal activity of the NK cells and the NO-iNOS regulation from splenocytes. The mass of body and the immune organs such as spleen and thymus were also studied. In OVX rats, body and thymus weights increased, however fucoidan supplementation did not change the body mass and organs weight compared to OVX group. Fucoidan supplementation increased NK cell activity and reduced NO-iNOS production in OVX rats. Ex vivo treatment of fucoidan increased NK cell activity in splenocytes from shame and OVX rats. Ex vivo, we confirmed that fucoidan partially reduced the NK cell activity in the presence of iNOS inhibitors in OVX-splenocytes. These results indicate fucoidan supplementation has a NK cell tumoricidal activity, which are regulated by the iNOS production in OVX rats. This suggests that fucoidan is useful for potential therapeutic strategies as a nutrient in regulating the NK cells in postmenopausal osteoporosis patients.
Objectives: The object of this study was to observe the complex anti-climacterium potentials of Yuklinzu aqueous extracts (YLZ), using bilateral ovariectomy (OVX) female ddY mice similar to women postmenopausal symptoms, as including cardiovascular diseases, obesity, hyperlipidemia, osteoporosis and hepatic steatosis. Methods: In order to evaluate anti-climacterium effects of YLZ, six groups of mice were used; sham control, OVX control, 17β-estradiol, YLZ 500, 250 and 125 mg/kg treated groups. Since 28 days after bilateral OVX surgery, YLZ were administered orally for 84 days, once a day. And then we evaluated anti-climacterium effects divided into five categories; estrogenic effects, anti-obesity, hypolipidemic effects, hepatoprotective effects and anti-osteoporotic effects. The results of YLZ were compared with 17β-estradiol 0.03 ㎍/head/day subcutaneous treated OVX mice. Results: As a result of OVX, obvious changes related to the estrogen-deficient menopausal symptoms - obesity, hyperlipidemia, hepatic steatosis and osteoporosis were displayed in mice. However, these menopausal symptoms induced by OVX were significantly inhibited by 84 days of consecutive treatment of 17β-estradiol, YLZ 500, 250 and 125 mg/kg, respectively. Especially, YLZ showed obvious dose-dependent inhibitory activities on the OVX-induced climacterium changes in mice, and YLZ 500 mg/kg showed comparable inhibitory effects against menopausal symptoms in comparison with those of 17β-estradiol 0.03 ㎍/head/day subcutaneous treatment. Conclusions: The results suggest that oral administration of YLZ 500, 250 and 125 mg/kg has obvious dose-dependent favorable anti-climacterium effects in OVX mice. Especially, YLZ 500 mg/kg showed comparable inhibitory effects against menopausal symptoms in comparison with those of 17β-estradiol 0.03 ㎍/head/day subcutaneous treatment.
Menopausal women experience urogenitory and vasomotor symptoms with increased risk of osteoporosis and cardiovascular diseases, which can be reduced by hormone replacement therapy. However unopposed estrogen therapy has been associated with an increased risk of endometrial hypeiplasia or cancer. The objectives of this study were to compare effects of continuous vs. sequential hormone replacement therapy (HRT) on lipid profile, bone mineral density and menopausal symptoms of postmenopausal women and to assess how they perceive the menopause and HRT culturally. In this retrospective study, women in menopause longer than 6 months, normal in the mam-mogram and Papanicolaou smear, cholesterol level lower than 190 mg/dL or triglyceride level lower 4han 500 mg/dL were treated with Srogen (conjugated equine estrogen 0.625 mg tablet) and Provera (medroxyprogesterone acetate 2.5 mg tablet) for continuous treatment(CT) or Cycloprogynova (Estradiol valerate 2 mg and Norgestrel 0.5 mg complex tablet) for sequential treatment(ST). They were evaluated for lipid profile, bone mineral density, menopausal symptoms, side effects and their perception of menopause and HRT. As results, total sixty-seven patients out of ninety-four enrollees were included in final analysis (33 in continuous therapy, 34 in sequential therapy). There were significant decrease in total cholesterol ($15.04\pm3.17$, p=0.0001), LDL ($19.72\pm3.27$, p=0.0001), and increase in HDL ($5.89\pm1.63$, p=0.0001). Bone minora) density increased significantly with HRT ($0.02\pm0.11$, p=0.0001). But, there were no significant differences in change of lipid profile between continuous and sequential therapy: Total cholesterol, $13.12\pm4.7\;vs.\;16.91\pm4.3;\;LDL\;20.53\pm4.1\;vs.\;18.93\pm5.12:HDL\;7.15\pm2.3\;vs.\;4.67\pm2.2,\;p>0.05$. Incidences of flush reduced from $75\%\;(CT)\;to\;3.13\%\;and\;71.88\%\;(ST)\;to\;9.35\%$. The change of endometrium and breast were found 3 (CT) and 5 (ST) women, respectively. Most of women recognized that HRT is necessary $(70\%)$ for postmenopausal period but did not understand well the cardiovascular protective effect. In conclusion, hormone replacement therapy was effective in improving lipid profile, bone mineral density and menopausal symptoms in both continuous and sequential treatments with similar efficacy.
Osteoporosis is one of the major health problem affecting postmenopausal women. Estrogen deficiency results in an increase in bone turnover, lead to bone resorption and an increase risk of fracture. The aim of this study was to evaluate the effects of Capsosiphon fulvecense extract (SCF) on the collagen content of the connective tissues and alkaline phosphatase activity of serum in ovariectomized estrogen-deficient rats. Three groups were surgically ovariectomized (OVX). The fourth group was sham operated. Sprague-Dawley female rats were randomly assigned to the following groups : sham-operated rats (Sham), ovariectomized control rats (OVX-control), ovariectomized rats supplemented with CsF at 50mg/kg body wt (OVX-CSF50) and ovariectomized rats supplemented with CsF at 200mg/kg body wt (OVX-CSF200). The Capsosiphon fulvecense extracts were orally administrated at 1mL per day. The ovariectomy caused a decreasing in the levels of collagen content in bone, cartilage, skin and lung tissues. However CSF groups, supplementation with Capsosiphon fulvecense extract, were increased the level of collagen content in bone, cartilage, skin and lung tissues than OVX-control group. Alkaline phosphatase activity also were increased and calcium levels were decreased than OVX-control on serum. These results suggest that Capsosiphon fulvecense supplementation prevents postmenopausal bone loss, thus it may be used possibly to improve the quality of life in menopausal women.
This study was done to evaluate the effect of dietary calcium level (a diet which met 100% or twice the calcium level in AIN-76 diet) on preventing bone loss in ovariectomized rats. Forty Sprauge-Dawley female rats(body weight 200$\pm$5g)were divided into two groups. One group were ovariecotomized (Ovx) while the others received sham operation(Sham). Thereafter, each rat group was further divided into normal calcium diet(0.52%) and high calcium diet(1.04%) subgroups. All rats were fed on experimental diet and deionized water ad libitum for 8 weeks. The total body, spine and femur bone mineral densities and bone mineral contents were measured by Dual Energy X-ray Absorptiometry, Eight weeks following operation, ovariectomized rats fed a high calcium diet had a significantly higher total bone mineral content, total bone calcium content, spine bone mineral density, spine bone mineral content and femur bone mineral content than ovariectomized rats fed control calcium diet. The correlation between dietary calcium intake level and spine bone mineral density were positive, but there was no correlation between dietary calcium intake and femur bone mineral density. The findings from the present study demonstrated that bone loss due to ovarian hormonal deficiency can be partially prevented by a high calcium diet. Futhermore, these findings support the strategy of the use of a high calcium diet in the prevention of estrogen depleted bone loss(postmenopausal osteoporosis)
Estrogen receptors (ERs) are steroid receptors located in the cytoplasm and on the nuclear membrane. The sequence similarities of human $ER{\alpha}$, mouse $ER{\alpha}$, rat $ER{\alpha}$, dog $ER{\alpha}$, and cat $ER{\alpha}$ are above 90%, but structures of $ER{\alpha}$ may different among species. Estrogen can be agonist and antagonist depending on its target organs. This hormone play roles in several diseases including breast cancer. There are variety of the relative binding affinity (RBA) of ER and estrogen species in comparison to $17{\beta}-estradiol$ (E2), which is a natural ligand of both $ER{\alpha}$ and $ER{\beta}$. The RBA of the estrogen species are as following: diethyl stilbestrol (DES) > hexestrol > dienestrol > $17{\beta}-estradiol$ (E2) > 17- estradiol > moxestrol > estriol (E3) >4-OH estradiol > estrone-3-sulfate. Estrogen mimetic drugs, selective estrogen receptor modulators (SERMs), have been used as hormonal therapy for ER positive breast cancer and postmenopausal osteoporosis. In the postgenomic era, in silico models have become effective tools for modern drug discovery. These provide three dimensional structures of many transmembrane receptors and enzymes, which are important targets of de novo drug development. The estimated inhibition constants (Ki) from computational model have been used as a screening procedure before in vitro and in vivo studies.
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