• The Journal of Korean Obstetrics and Gynecology
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• v.31 no.4
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• pp.16-38
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• 2018

Objectives: The objective of this in vivo study is to observe the anti-osteoporotic activities of Gojineumja aqueous extracts (GJEJ) on the ovariectomized (OVX) mice as compared to those of risedronate sodium (RES). Methods: Thirty five days after bilateral OVX, GJEJ was orally administered, for 35 days once a day and then the changes on the body weight and gain during experimental periods, femur weights, bone mineral density (BMD), bone strength (failure load), mineral contents - calcium (Ca) and inorganic phosphorus (IP), histological profiles and histomorphometrical analyses at sacrifice were conducted with serum biochemistry - osteocalcin contents and bone specific alkaline phosphatase (BALP) activities. And the results of GJEJ were compared with RES orally administered OVX mice. Results: As a result of OVX, noticeable increase of body weight and gains and serum osteocalcin levels, decrease of serum BALP activities, femur weights, femur Ca and IP contents, BMD and strength were observed as compared to those of sham control mice, respectively. Also, the decrease of all histomorphometrical indices indicating the bone mass and structure, and the increase of indices about resorption were also detected in the femur of OVX control. However, these estrogen-deficient osteoporotic signs were significantly and dose-dependently inhibited by 35 days of continuous oral treatment of GJEJ, at dose levels of 500, 250 and 125 mg/kg, respectively. Especially, GJEJ 500 mg/kg showed favorable inhibitory activities against estrogen-deficient osteoporosis symptoms induced by OVX as comparable to those of RES 2.5 mg/kg. Conclusions: The results in this study suggest that oral administrations of GJEJ have clear dose-dependent favorable anti-osteoporotic activities in OVX mice.

• Journal of Physiology & Pathology in Korean Medicine
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• v.26 no.2
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• pp.160-165
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• 2012

Osteoporotic fracture became a serious social problem, which related with mortality and morbidity in old age population. Osteoclast which is responsible for bone resorption is originated from hematopoietic cell line and plays a key role osteoporotic bone loss. Cynanchum wilfordii (Asclepiadaceae) roots have been used in Korean folk medicine for the treatment of diabetes mellitus and aging progression. Also, recent studies have shown that the extract and fractions of Cynanchi Wilfordii Radix have various pharmacological actions including scavenging free radicals, enhancing immunity, reducing high serum cholesterol, and anti-tumor activity. However, the effect of extract of Cynanchi Wilfordii Radix in osteoclast differentiation had not been reported. Thus, we evaluated the effect of Cynanchi Wilfordii Radix on receptor activator of nuclear factor-${\kappa}B$ ligand (RANKL)-induced osteoclast differentiation. Through our study, we found that Cynanchi Wilfordii Radix significantly inhibited osteoclast differentiation induced by RANKL. Cynanchi Wilfordii Radix suppressed the activation of p38 pathway and $NF{\kappa}B$ in bone marrow macrophages (BMMs) treated with RANKL. Also, Cynanchi Wilfordii Radix significantly inhibited the mRNA expression of c-Fos, tartrate-resistant acid phosphatase (TRAP), osteoclast-associated receptor (OSCAR), nuclear factor of activated T cells (NFAT)c1 and cathepsin K in BMMs treated with RANKL. Particularly, Cynanchi Wilfordii Radix inhibited the protein expression of c-fos and NFATc1. Taken together, our results demonstrated that Cynanchi Wilfordii Radix may be useful treatment option of bone-related disease such as osteoporosis leads to fracture of bone and rheumatoid arthritis.

• Journal of Korean Dental Science
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• v.8 no.2
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• pp.65-73
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• 2015

Purpose: Parathyroid hormone (PTH) therapy has drawn attention, as an alternative to anti-resorptive drugs since PTH accelerates bone density by anabolic action. The purpose of this study was to identify the effect of intermittent PTH administration on jaw bones of rat undergone bilateral ovariectomy. Materials and Methods: Nine female Sprague-Dawley rats were divided into three groups. PTH group was ovariectomized (OVX) to induce osteoporosis and PTH $30{\mu}g/kg$ was administered 1 week after the surgery. In OVX group, ovariectomy was performed and only vehicle was administered by subcutaneous injection 3 times per week. Control group was subjected to sham surgery. The animals were sacrificed 8 weeks after the surgery and specimens were obtained from ilium and upper and lower jaw bones. Histological investigation was carried out by using an optical microscope and micro-computed tomography was taken to examine structural property changes in each bone sample. Result: In the ilium, the bone volume ratio (bone volume/total volume, BV/TV) of PTH, OVX and control groups was $53.75%{\pm}7.57%$, $50.61%{\pm}12.89%$, $76.20%{\pm}5.92%$ (P=0.061) and bone mineral density (BMD) was $1.12{\pm}0.09$, $0.88{\pm}0.48$, $1.38{\pm}0.07g/cm^3$ (P=0.061). In the mandible, BV/TV of PTH, OVX and control groups was $64.60%{\pm}12.17%$, $58.26%{\pm}9.63%$, $67.54%{\pm}14.74%$(P=0.670) and BMD was $1.21{\pm}0.17$, $1.19{\pm}0.13$, $1.27{\pm}0.18g/cm^3$ (P=0.587). In the maxilla, BV/TV of PTH, OVX and control groups was $61.19%{\pm}8.92%$, $52.50%{\pm}11.22%$, $64.60%{\pm}12.17%$ (P=0.430) and BMD was $1.20{\pm}0.11$, $1.11{\pm}0.16$, $1.21{\pm}0.17g/cm^3$ (P=0.561). No statistically significant difference was found in any variables in all groups. Histological observation revealed that the ilium in OVX group demonstrated sparsely formed trabecular bones compared with other groups. However, upper and lower trabecular bones did not present significant differences. Conclusion: Intermittent administration of PTH appears to affect the microstructure of rat jaw bones, but statistical significance was not found. However, the measurements in this study partly implicated the possible anabolic effect of PTH in vivo.

• Journal of Acupuncture Research
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• v.34 no.2
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• pp.1-18
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• 2017

Objectives : The purpose of this study was to evaluate the effects of water extracts of Eucommiae cortex (EC), Psoraleae semen (PS), and their combination on receptor activator of nuclear factor-kappa-B ligand (RANKL)-induced osteoclast differentiation. Methods : We assayed the protein expression levels of nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1), c-Fos, mitogen-activated protein kinases (MAPKs), and ${\beta}-actin$ in cell lysates using western blotting. Similarly, mRNA expression levels of NFATc1, c-Fos, tartrateresistant acid phosphate (TRAP), and glyceraldehyde-3-phosphate dehydrogenase, spermatogeni (GAPDHS) from bone marrow macrophages (BMMs) were analyzed using reverse transcription-polymerase chain reaction (RT-PCR). Furthermore, we determined the anti-osteoporotic effects of the water extracts of EC, PS, and their combination in a lipopolysaccharide (LPS)-induced bone-loss mouse model. Results : The in vitro data revealed showed that the combination of EC and PS extract showed a more remarkable inhibition of osteoclast differentiation than each herb did alone. The combination downregulated the induction of c-Fos, NFATc1, and TRAP by suppressing the phosphorylation of p38 and c-Jun N-terminal kinases (JNKs) and inhibiting nuclear factor kappa-light-chain-enhancer of activated B cells ($NF-{\kappa}B$). Lastly, the in vivo data showed that PS reduced the LPS-induced bone erosion. Conclusion : The result of this study suggests that EC and PS could be potential therapeutic agents for bone loss diseases such as osteoporosis.

• Journal of Physiology & Pathology in Korean Medicine
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• v.28 no.1
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• pp.29-34
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• 2014

Bone homeostasis is maintained by balance between bone resorbing-osteoclasts and bone forming-osteoblasts. Excessive osteoclastic bone resorption plays a critical role in bone destruction in pathological bone diseases such as osteoporosis, rheumatoid arthritis, and periodontal disease. Many compounds derived from natural products have pharmacological applications and have therapeutic value for treating or preventing several bone diseases characterized by excessive bone resorption. To discover new compounds that can act as anti-resorptive agents, we screened for natural compounds that regulate osteclast differentiation, and found that water extract of Ziziphus Jujuba Mill (WEZJ) has inhibitory effects on osteoclast differentiation. In this study, WEZJ clearly inhibits the osteoclast differentiation in the presence of receptor activator of nuclear factor kB (RANKL), macrophage colony-stimulating factor (M-CSF) without cytoxicity by blocking activation of nuclear factor of activated T cells (NFAT)c1, and c-Fos. In signaling pathway, the phosphorylation of Akt, p38, c-Jun N-terminal kinases (JNK), extracellular signal-regulated kinases (ERK) and the expression of osteoclast-associated receptor (OSCAR), tartrate-resistant acid phosphates (TRAP), Integrin av, Integrin b3, Cathepsin K are suppressed, too. These result suggest that WEZJ may have therapeutic value for treating or preventing several bone diseases characterized by excessive bone destruction.

• Journal of Embryo Transfer
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• v.30 no.3
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• pp.201-206
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• 2015

Selenium (Se) is an essential trace element for humans and animals, and several findings suggest that dietary Se intake may be necessary for bone health. Accumulating evidence indicates that Se compounds possess anticancer properties. Se is specifically incorporated into proteins in the form of selenocysteine and non-specifically incorporated as selenomethionine in place of methionine. This study evaluated protection by Se in the bone repair process in ovariectomized rats after irradiation. For such purpose, 80 ovariectomized female Sprague-Dawley rats were randomly divided into 4 experimental groups: ovariectomized (Ov), Ov/Se, Ov/irradiated (Irr) and Ov/ Se/Irr. A bone defect was created on the tibia of all animals 40 days after ovariectomy. Two days after surgery, only the Ov/Se and Ov/Se/Irr rats received 0.8 mg Se/kg. Three days after surgery, only the Ov/Irr and Ov/Se/Irr rats received 10 Gy of X-rays on the lower limb region. The animals were euthanized at 7, 15, 22 and 29 days after surgery to assess the repair process, which was evaluated by analysis of trabecular bone number (Masson Trichrome) and birefringence analysis (Picrosirius). It was possible to observe a delay in the bone repair process in the ovariectomized/irradiated group and similarity between the ovariectomized, Ov/ Se and Ov/Se/Irr groups. Our findings suggest that sodium selenite may influence a radioprotective effect in the bone repair of tibia of ovariectomized rats without toxicity.

• Journal of Oriental Neuropsychiatry
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• v.20 no.3
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• pp.205-216
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• 2009

Objectives : To establish the fundaments for EBM of Traditional Korean Medicine, the papers on Guibi-tang(Guipitang) which were frequently used in medical institutions of Traditional Korean Medicine were analyzed through researching domestic and international literatures. Methods : The papers were classified by the year of publishment, by experimental methods, by laboratory animals used in biological experiment and by the kinds of studies on biological efficacy. Results : Of total 39 papers were registered in domestic journals. Since 1980, publishments of papers have continuously increased. The papers on biological studies were 34 volumes, clinical studies were 5 volumes. Biological studies mainly showed the effects of anti-stress, anti-oxidant, hemostasis, anti-osteoporosis, gastroprotection, reproductive ability, brain cell activity, radioprotection. And clinical studies showed improvements of fearful throbbing, memory and orientation, insomnia, vericose vein, schizophrenia. Conclusions : Guibi-tang(Guipitang) could be used to fortify the spleen, nourish the heart and then control the blood. However biological studies need to be conducted in accordance with clinical study and further clinical studies on randomized controlled trials should be proceeded.

• Journal of Ginseng Research
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• v.45 no.4
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• pp.482-489
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• 2021

Background: Asthma is an incurable hyper-responsive disease of the pulmonary system that is caused by various allergens, including indoor and outdoor stimulators. According to the Global Asthma Network, 339 million people suffered from asthma in 2018, with particularly severe forms in children. Numerous treatments for asthma are available; however, they are frequently associated with adverse effects such as growth retardation, neurological disorders (e.g., catatonia, poor concentration, and insomnia), and physiological disorders (e.g., immunosuppression, hypertension, hyperglycemia, and osteoporosis). Methods: Korean Red Ginseng has long been used to treat numerous diseases in many countries, and we investigated the anti-asthmatic effects and mechanisms of action of Korean Red Ginseng. Eighty-four BALB/c mice were assigned to 6 treatment groups: control, ovalbumin-induced asthma group, dexamethasone treatment group, and 3 groups treated with Korean Red Ginseng water extract (KRGWE) at 5, 25, or 50 mg/kg/day for 5 days. Anti-asthmatic effects of KRGWE were assessed based on biological changes, such as white blood cell counts and differential counts in the bronchoalveolar lavage fluid, serum IgE levels, and histopathological changes in the lungs, and by examining anti-asthmatic mechanisms, such as the cytokines associated with Th1, Th2, and Treg cells and inflammation pathways. Results: KRGWE affected ovalbumin-induced changes, such as increased white blood cell counts, increased IgE levels, and morphological changes (mucous hypersecretion, epithelial cell hyperplasia, inflammatory cell infiltration) by downregulating cytokines such as IL-12, IL-4, and IL-6 via GATA-3 inactivation and suppression of inflammation via NF-κB/COX-2 and PGE₂ pathways. Conclusion: KRGWE is a promising drug for asthma treatment.

• Journal of Nutrition and Health
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• v.51 no.4
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• pp.316-322
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• 2018

Purpose: The Glycyrrhiza uralensis species (Leguminosae) as a medicinal biocompound, and one of its root components, isoliquritigenin (ISL), which is a flavonoid, has been reported to have anti-tumor activity in vitro and in vivo. However, its function in bone formation has not been studied yet. In this study, we tested the effect of Glycyrrhiza uralensis (ErLR) and baked Glycyrrhiza uralensis (EdLR) extracts on osteoblast proliferation, alkaline phosphatase (ALP) activity, and bone-related gene expression in osteoblastic MC3T3-E1 cells. Methods: MC3T3-E1 cells were cultured in various levels of ErLR (0, 5, 10, 15, $20{\mu}g/mL$), EdLR (0, 5, 10, 15, $20{\mu}g/mL$), or ISL (0, 5, 10, 15, $20{\mu}M$) in time sequences (1, 5, and 20 days). Also, isoliquritigenin (ISL) was tested for comparison to those two biocompound extracts. Results: MTT assay results showed that all three compounds (ErLR, EdLR, and ISL) increased osteoblastic-cell proliferation in a concentration-dependent manner for one day. In addition, both ErLR and EdLR compounds elevated the osteoblast proliferation for 5 or 20 days. Extracellular ALP activity was also increased as ErLR, EdLR, and ISL concentration increased at 20 days, which implies the positive effect of Glycyrrhiza species on osteoblast mineralization. The bone-related marker mRNAs were upregulated in the ErLR-treated osteoblastic MC3T3-E1 cells for 20 days. Bone-specific transcription factor Runx2 gene expression was also elevated in the ErLR- and EdLR-treated osteoblastic MC3T3-E1 cells for 20 days. Conclusion: These results demonstrated that Glycyrrhiza uralensis extracts may be useful for preventing osteoporosis by increasing cell proliferation, ALP activity, and bone-marker gene expression in osteoblastic cells.

• Journal of Nutrition and Health
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• v.36 no.5
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• pp.452-458
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• 2003

Soybean is a rich source of isoflavones such as genistein and daidzein. Soy isoflavones have both weak estrogenic and anti-estrogenic effects and are structurally similar to tamoxifen, an agent that has an effect similar to that of estrogen in terms of reducing postmenopausal bone loss. The purpose of this study was to determine the effects of differences in protein source (casein vs soy) and isoflavone levels (reduced vs higher levels) on selected bone markers and hormones in growing male rats. Thirty weanling Sprague-Dawley young rats were divided into 3 groups: The control group was fed a casein-based diet, the soy concentrate group was fed soy protein with totally reduced isoflavones content (isoflavones 0.07 mg/g protein), and the soy isolate group was fed soy protein with a higher than normal isoflavones content (isoflavones 3.4 mg/g protein). The degree of bone formation was estimated by measuring serum osteocalcin and alkaline phosphoatase (ALP). By determining collagen cross-linkage by immunoassay and correcting with creatinine values, the bone resorption rate was compared. Serum osteocalcin, growth hormone, estrogen and calcitonin were analyzed using radio immunoassay kits. The bone formation marker and ALP activity were differentiated by protein source, showing higher values than casein in feeding either soy isolate or soy concentrate. In this study using growing rats, the differences in isoflavone contents were not a significant factor in either bone formation or bone reaborption markers. Moreover, the soy isolate group had significantly higher levels of growth hormone than the casein group. The findings of this study suggest that growth hormone is partially responsible for its bone-formation effects in young growing rats. Soy protein and the isoflavones in soy protein are beneficial for bone-formation in growing male rats. Therefore, exposure to soy protein and isoflavones early in life may have long-term health benefits in preventing bone diseases such as osteoporosis. Further study to evaluate the mechanism of action of isoflavones on bones is warranted. (Korean J Nutrition 36(5): 452∼458, 2003)