• Korean Journal of Plant Resources
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• v.27 no.6
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• pp.593-600
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• 2014

Osteoporosis is a progressive bone disease characterized by low bone mass which is caused by disturbance in the balance between the activities of osteoblasts and osteoclasts. Postmenopausal osteoporosis is one of the most common disorders in women after menopause, which is linked to an estrogen deficiency and characterized by an excessive loss of trabecular bone. Rubus coreanus has been used for their various pharmacological properties in Asia as a traditional medicine. To investigate the effect of unripe fruits of R. coreanus 30% ethanol extract (RCE) on osteoblast-like cells (MG63) differentiation, we examined the effects of RCE on in vitro osteoblastic differentiation markers, alkaline phosphatase (ALP) activity and receptor activator of nuclear factor ${\kappa}$-B ligand (RANKL) and osteoprotegerin (OPG) expression. The high concentration (50 and $100{\mu}g/mL$) of RCE markedly increased ALP activity, whereas decreased the RANKL/OPG. We also investigated the effect of RCE on M-CSF plus RANKL-induced differentiation of pre-osteoclast cells (RAW 264.7). RCE treatment remarkably inhibited M-CSF/RANKL-induced formation of osteoclast-like multinuclear cells from RAW 264.7 cells. Moreover, the inhibitory effect of RCE was reduced by selective estrogen receptor-${\alpha}$ antagonist. Our research suggests that suggested that unripe fruits of R. coreanus may act beneficial effects on bone mass by regulating both osteoblast and osteoclast.

• Journal of Life Science
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• v.25 no.1
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• pp.113-120
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• 2015

Osteoporosis is a major bone disorder defined as having bone mineral density (BMD) of 2.5 standard deviations or more below the peak bone mass. Osteoporosis will increasingly be a major disorder that faces the aging mankind. It is the result of an imbalance in the bone remodeling system, where bone constantly undergoes a cycle of resorption by osteoclasts and formation by osteoblasts. Estrogen deficiency in women following menopause is identified as the predominant reason that causes disparity in this system. Current medical treatments for osteoporosis include hormone replacement therapy (HRT), biphosphonates, and teriparatide, but have various side effects that raise questions concerning their medical safety and practicality. Alternative treatments involving natural product sources are under study to find a safer therapy. Many natural sources including lactoferrin and isoflavones and numerous traditional herbal medicines exhibit anti-resorptive or anabolic effects on bone and thus show promises to provide therapeutic agents in treating osteoporosis. Unfortunately, the majority of natural product treatments are still in its preliminary stages to prove their efficacy even though the development pace of treatment for osteoporosis is astounding in the past few decades. Further progress in pre-clinical studies and the subsequent clinical studies will someday lead to a breakthrough that takes us another step forward in science.

• The Korea Journal of Herbology
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• v.37 no.5
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• pp.1-8
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• 2022

Objectives : This study aimed to investigate the synergistic effect of combining Cynanchi Wilfordii Radix extract with Humuli Lupuli Flos extract on estrogenic and anti-osteoclastogenic activity. Methods : Estrogenic effect of a mixture of Cynanchi Wilfordii Radix extract and Humuli Lupuli Flos extract (CWHL), Cynanchi Wilfordii Radix extract, Humuli Lupuli Flos extract, caudatin (an active ingredient of Cynanchi wilfordii Radix extract) and 8-prenylnaringenin (an active ingredient of Humuli Lupuli Flos extract) were examined by proliferation E-screen assay and expression of estrogen inducible gene, pS2 via Real Time-PCR (RT-PCR) in MCF-7 estrogen responsive cells. And their estrogenic activities were investigated how to modulate Estrogen receptor 𝛽 by binding affinity assay. Inhibitory effect of CWHL, Cynanchi Wilfordii Radix extract, Humuli Lupuli Flos extract, caudatin and 8-prenylnaringenin on RANKL-induced osteoclast differentiation were tested by TRAP (Tartrate-resistant acid phosphatase) staining in osteoclastogenic RAW 264.7 cells. Results : CWHL, Humuli Lupuli Flos extract and 8-prenylnaringenin accelerated the proliferation of MCF-7 and the expression of pS2 in MCF-7. CWHL, Cynanchi Wilfordii Radix extract, Humuli Lupuli Flos extract, caudatin and 8-prenylnaringenin bind to estrogen receptor 𝛽. CWHL, Cynanchi Wilfordii Radix extract, Humuli Lupuli Flos extract, caudatin and 8-prenylnaringenin inhibited RANKL-induced osteoclastogenesis in osteoclastogenic RAW 264.7. CWHL is more effective for all markers than Cynanchi Wilfordii Radix extract or Humuli Lupuli Flos extract alone. Conclusions : CWHL may a potential therapeutic agent for menopause and osteoporosis as a natural food resource. CWHL as a natural food source has therapeutic potential in cases of menopause and osteoporosis.

• Journal of Microbiology and Biotechnology
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• v.16 no.1
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• pp.37-45
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• 2006

Treatment with exopolymers of Aureobasidium pullulans SM-2001 containing $\beta-1,3/1,6-glucan$ inhibited osteoclastogenesis of bone marrow stem cells in a co-culture system with calvariae osteoblastic cells. In addition, the treatment increased mineral deposition in osteoblastic cells. These two observations prompted us to evaluate whether the exopolymers could be used as an anti-osteoporotic agent, and efficacy of the exopolymers to prevent bone loss was compared with alendronate, a bisphosphonate, in ovariectomized mice prone to osteoporosis. Administration of the exopolymers to the ovariectomized mice resulted in improved effects on femur weight and histomorphometric changes of femur such as trabecular bone volume (TBV), trabecular bone thickness (TBT), and cortical bone thickness (CBT). In conclusion, the exopolymers treatment inhibited bone loss from osteoporosis induced by ovariectomy, and the effect was comparable to alendronate administration.

• Biomedical Science Letters
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• v.20 no.3
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• pp.156-161
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• 2014

It has been reported that safflower seeds have preventive effects against osteoporosis. Recently, safflower buds (SB) were found to have more useful functional ingredients than safflower seeds. In the current study, we evaluated the anti-osteoporosis effects of SB diet in ovariectomized (OVX) rats. The rats were divided into five groups; sham operated group, OVX alone group, OVX plus $17{\beta}$-estradiol ($E^2$ $10{\mu}g/kg$, i.p.) and OVX plus SB diet feeding group (0.3% or 1%). Feeding of SB diet (0.3% or 1%) to OVX rats markedly increased bone mineral density (BMD) of femurs, compared to the OVX group. The OVX rats exhibited a marked increase in trabecular separation (Tb.Sp) and this change was inhibited by the feeding of SB diet, similar to that seen with OVX+E2 group. Moreover, feeding of SB diet to OVX rats decreased the markers of bone turnover, including osteocalcin and alkaline phosphatase (ALP). These results suggest that SB extract has a bone sparing effect in OVX-induced trabecular bone loss and prevents deterioration of bone microarchitecture by suppressing the rate of bone turnover. Therefore, SB may be useful for preserving bone mass and structure in estrogen deficient women with a potential role in reducing postmenopausal osteoporosis.

• Journal of Physiology & Pathology in Korean Medicine
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• v.25 no.1
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• pp.109-114
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• 2011

Atractylodis Rhizoma Alba is commonly used herbal medicine and it has been known that has immuno-regualtory effects and anti-cancer effects. The inhibition of osteoclastogenesis is essential for the prevention and treatment of osteoporosis. The aim of this study was to evaluate the effects of Atractylodis Rhizoma Alba on osteoclast differentiation in vitro and on resorbing activity of osteoclast. Osteoclast formation was evaluated in bone marrow cells (BMC) in the presence or absence of Atractylodis Rhizoma Alba. The expression of c-fos, tartrate-resistant acid phosphatase (TRAP), OSCAR, DC-STAMP, cathepsin K, MafB and NFATc1 mRNA in osteoclast precursor were assessed by RT-PCR. The levels of TNF receptor-associated factor-6 (TRAF-6), c-fos and NFATc1 protein were assessed by Western blot analysis. Also the correlation with MAPKs and NF-${\kappa}B$ pathways were measured by using Western blot analysis. With bone resorption study, I tried to evaluate the inhibitory effects of Atractylodis Rhizoma Alba on mature osteoclast function. Atractylodis Rhizoma Alba inhibited the RANKL induced osteoclastic differentiation from bone marrow macrophage in a dose dependant manner without cellular toxicity. Gene expression of c-fos and NFATc1 was significantly down regulated with Atractylodis Rhizoma Alba treatment. Atractylodis Rhizoma Alba markedly inhibited the RANKL-induced osteoclastogenesis through suppression of nuclear factor kappa b (NF-${\kappa}B$) pathway, down stream pathway of p38, ERK and JNK pathway. Taken together, I concluded that Atractylodis Rhizoma Alba have beneficial effect on osteoporosis by inhibition of osteoclast differentiation and by inhibition of functioning osteoclast. Thus I expect that Atractylodis Rhizoma Alba could be a treatment option for osteoporosis.

• The Korean Journal of Physiology and Pharmacology
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• v.23 no.1
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• pp.47-54
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• 2019

Estrogen withdrawal in post-menopausal women leads to overactivation of osteoclasts, which contributes to the development of osteoporosis. Inflammatory cytokines are known as one of mechanisms of osteoclast activation after estrogen deficiency. SPA0355 is a thiourea derivative that has been investigated for its antioxidant and anti-inflammatory activities. However, its efficacy in bone resorption has not been previously investigated. The aim of this study was to investigate the impact of SPA0355 on the development of osteoporosis and to explore its mode of action. In vitro experiments showed that SPA0355 inhibited receptor activator of $NF-{\kappa}B$ ligand (RANKL)-induced osteoclastogenesis in primary bone marrow-derived macrophages. This effect appears to be independent of estrogen receptor activation as ICI 180,782 failed to abrogate its effects on osteoclasts. Further signaling studies revealed that SPA0355 suppressed activation of the MAPKs, Akt, and $NF-{\kappa}B$ pathways. SPA0355 also increased osteoblastic differentiation, as evidenced by its effects on alkaline phosphatase activity and mineralization nodule formation. Intraperitoneal administration of SPA0355 to ovariectomized mice prevented bone loss, as verified by three-dimensional images and bone morphometric parameters derived from ${\mu}CT$ analysis. Noticeably, SPA0355 did not show hepatotoxicity and nephrotoxicity and also had little effect on hematological parameters. Taken together, the results indicate that SPA0355 may protect against bone loss in ovariectomized mice by stimulation of osteoblast differentiation and by inhibition of osteoclast resorption. Therefore, SPA0355 is a safe and potential candidate for management of postmenopausal osteoporosis.

• Journal of the Korean Chemical Society
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• v.67 no.2
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• pp.120-128
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• 2023

Osteoporosis is a disease that causes the weakening of bone by increasing porosity, which often results in fractures. Osteoporosis treatment measures include the use of Bisphosphonates and estrogen. However, these treatments cannot be used in the long term as these treatments have adverse side effects. Therefore, there is a need to identify better and safer treatment options. For this, 63 plant extracts were screened and among them, six extracts showed high anti-osteoclastic activity with low cytotoxicity. Of these six extracts, three extracts, Cudrania tricuspidata (P371), Ulmus davidiana var. japonica (P401), and Torilis japonica (P411), showed more than 50 percent osteoclast inhibition. While the remaining, Stewartia pseudocamellia extracts I and II (P370, P397) and Cuscuta chinensis (P418), showed moderate or between 40-50 percent osteoclast inhibition. Among all the extracts, Torilis japonica (P411) showed the highest inhibitory action against osteoclast development. Torilis japonica (P411) primary components include Kaempferol, Quercetin, and Luteolin, all proven to inhibit osteoclastogenesis. Stewartia pseudocamellia extracts I and II (P370 and P397) showed moderate or 44% osteoclast inhibition. Stewartia pseudocamellia extract II (P397) enhanced the growth of RAW 264.7 cells by 19%. Torilis japonica (P411) and Stewartia pseudocamellia extract II (P397) suppressed the expression of osteoclast-specific genes in RANKL-induced osteoclastogenesis in RAW 246.7 cells. Torilis japonica (P411) extracts even increased osteoblast-specific RUNX2 gene expression. This results provide that six extracts could be used as a potential treatment option for osteoporosis disease with the extracts of Torilis japonica (P411) and Stewartia pseudocamellia (P397) as an ideal candidates. However, the combination of the extract with higher osteoclastic inhibition and less toxic effects with further analysis should be recommended.

• Food Science of Animal Resources
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• v.43 no.4
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• pp.712-720
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• 2023

Osteoporosis is a growing global health concern primarily associated with decreased estrogen in postmenopausal women. Recently, some strains of probiotics were examined for potential anti-osteoporotic effects. This study intended to evaluate the impacts of Lactiplantibacillus plantarum MGE 3038 strain (MGE 3038) in ovariectomized rats. For this purpose, twelve weeks old female Wistar rats (n=21; 250-300 g) were divided into 3 groups; ovariectomy (OVX) group, OVX/MGE 3038 group and Sham group (control). In these groups; two went through respective OVX and one had daily MGE 3038 administration through oral gavage. Prior to 16 weeks after OVX, we collected blood samples and extracted the tibiae. We scanned the extracted tibiae by in-vivo micro-computed tomography (micro-CT) and evaluated pathology by hematoxylin and eosin (H&E) and Masson's trichrome staining. The serum levels of C-telopeptide of type I collagen (CTX), osteocalcin (OC), and the receptor activator of nuclear factor-κB ligand (RANKL) were examined. The OVX/MGE 3038 group showed increases in bone mineral density, trabecular bone volume, trabecular number, and trabecular thickness (Tb.Th), and a decrease in trabecular spacing than the OVX group. However, OVX/MGE 3038 group and control group were measurably comparable in Tb.Th. Micro-CT, H&E, and Masson's trichrome findings exhibited increased preservation and maintenance of trabecular bone structure in the OVX/MGE 3038 group in comparison to the OVX group. In serum, the levels of CTX, OC and RANKL were significantly different between the OVX and OVX/MGE 3038 groups. Taken together, L. plantarum MGE 3038 could be helpful for the treatment of osteoporosis.

• Journal of Microbiology and Biotechnology
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• v.33 no.9
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• pp.1197-1205
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• 2023

Osteoporosis, Greek for "porous bone," is a bone disease characterized by a decrease in bone strength, microarchitectural changes in the bone tissues, and an increased risk of fracture. An imbalance of bone resorption and bone formation may lead to chronic metabolic diseases such as osteoporosis. Wolfiporia extensa, known as "Bokryung" in Korea, is a fungus belonging to the family Polyporaceae and has been used as a therapeutic food against various diseases. Medicinal mushrooms, mycelium and fungi, possess approximately 130 medicinal functions, including antitumor, immunomodulating, antibacterial, hepatoprotective, and antidiabetic effects, and are therefore used to improve human health. In this study, we used osteoclast and osteoblast cell cultures treated with Wolfiporia extensa mycelium water extract (WEMWE) and investigated the effect of the fungus on bone homeostasis. Subsequently, we assessed its capacity to modulate both osteoblast and osteoclast differentiation by performing osteogenic and anti-osteoclastogenic activity assays. We observed that WEMWE increased BMP-2-stimulated osteogenesis by inducing Smad-Runx2 signal pathway axis. In addition, we found that WEMWE decreased RANKL-induced osteoclastogenesis by blocking c-Fos/NFATc1 via the inhibition of ERK and JNK phosphorylation. Our results show that WEMWE can prevent and treat bone metabolic diseases, including osteoporosis, by a biphasic activity that sustains bone homeostasis. Therefore, we suggest that WEMWE can be used as a preventive and therapeutic drug.