• Journal of Physiology & Pathology in Korean Medicine
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• v.27 no.4
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• pp.431-436
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• 2013

Bone homeostasis is maintained by co-ordination of bone-resorbing osteoclasts and bone-forming osteoblasts. Imbalance between osteoclasts and osteoblasts leads to many bone diseases such as osteoporosis, rheumatoid arthritis. Taxillus chinensis is a herb that has been widely used to improve bone health. However, the effect and mechanism of Taxillus chinensis extract on osteoclast differentiation and bone resportion has been unknown. Thus, We investigated the effect of Taxillus chinensis on expression of receptor activator of nuclear factor-${\kappa}B$ ligand (RANKL)-induced osteoclast differentiation and bone resorption. Also, the action of Taxillus chinensis on mechanisms relating to osteoclast differentiation was studied. In this results, we identified that Taxillus chinensis significantly inhibited RANKL-induced osteoclast differentiation and bone resportion. Moreover, Taxillus chinensis was suppressed the activation of NF-${\kappa}B$ in bone marrow macrophage treated RANKL and M-CSF. Taxillus chinensis was down-regulated the mRNA expression of c-Fos, nuclear factor of activated T-cells (NFAT)c1, osteoclast-associated receptor (OSCAR), tartrate-resistant acid phosphatase (TRAP). The cell adhesion-related molecules such as integrin ${\alpha}v$ and integrin ${\beta}3$, and the filamentous actin (F-actin) rings of mature osteoclasts-related molecules such as dendritic cell-specific transmembrane preotein (DC-STAMP) and cathepsin K are also suppressed. Taken together, these results indicated that Taxillus chinensis will be a good candidate to treat osteoclast-mediated bone diseases.

• Journal of muscle and joint health
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• v.5 no.1
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• pp.83-109
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• 1998

This study was carried out to identify the Important modifiable risk factors for reduced bone mass and to construct prediction model which can classify women with either low or high bone mass. Through the literature review, individual characteristics such as age, body weight, height, education level, family history, age of menarche, postmenopausal period, gravity, parity, menopausal status, and breast feeding period were identified and factors of life style such as past milk consumption, past physical activity, present daily activity, present calcium intake, alcohol intake, cigarette smoking, coffee consumption were identified as influencing factors of reduced bone mass in women. Four hundred and eighty women aged between 28 and 76 who had given measurement bone mineral density by dual energy x-ray absortiometry in lumbar vertebrae and femur from July to October, 1997 at 4 general hospitals in Seoul and Pusan were selected for this study. Women were excluded if they had a history of any chronic illness such as rheumatoid arthritis, diabetes mellitus, hyperthroidism, & gastrointestinal disorder and any medication such as calcium supplements, calcitonin, estrogen, thyroxine, antacids, & corticosteroids known affect bone. As a result of these exclusion criteria, four hundred and seventeen women were used for analysis. Multiple logistic regression model was developed for estimating the likelihood of the presence or absence of reduced bone mass. A SAS procedure was used to estimate risk factor coefficient. The results are as follows For lumbar spine, the variables significant were age, body weight, menopause status, daily activity, past milk consumption, and past physical activity(p<0.01), while for femoral Ward's triangle, age, body weight, level of education, past milk consumption, past physical activity(p<0.001). Past physical activity, present daily activity and past milk consumption are the most powerful modifiable predictors in vertebrae and femur among the predictors. When the model performance was evaluated by comparing the observed outcome with predicted outcome, the model correctly identified 74.1% of persons with reduced bone mass and 84.5% of persons with normal bone mass in the lumbar vertebrae and 82.9% of persons with reduced bone mass and 75.0% of persons with normal bone mass in the femoral Ward's triangle. On the basis of these results, a number of recommendations for the management of reduced bone mass may be made : First, those woman who are classified as high risk group of the reduced bone mass in the prediction model should examine the bone mineral density to further examine the usefulness of this model. Second, the optimal amount of milk consumption and a regular weight bearing exercise in childhood, adolescence, and early adult should be ensured.

• Journal of Acupuncture Research
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• v.32 no.3
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• pp.1-13
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• 2015

Purpose : This research was conducted to investigate the effect of sweet bee venom pharmacopuncture and low level laser acupuncture on paw edema, pain index, anti-inflammatory factor, AST, ALT and complete blood cell count of a rat model with Complete Freund's Adjuvant-induced arthritis. Methods : Five experimental groups were formed with each consisting of six rats: normal group, control group, sweet bee venom pharmacopuncture group, lower level laser acupuncture group, and sweet bee venom pharmacopuncture, lower level laser acupuncture group. The experimental model of arthritis was induced by two injections of Freund's adjuvant into the left knee joint of Sprague Dawley(SD) rats. The second injection of Freund's adjuvant was given ten days after the first one. Ten days later, sweet bee venom pharmacopuncture and low level laser acupuncture were administered separately or together by assigned groups at $GB_{34}$ and $GB_{39}$ of rats twice a week for a total of six times. Thereafter, edema rate, pain index, tumor necrosis factor-${\alpha}$, interleukin-6, aspartate aminortansferase, alanine aminotransferase and complete blood cell count were measured. Results : We noticed synergic effects of sweet bee venom pharmacopuncture and low level laser acupuncture according to the results of the paw edema and Von Frey pain index. The sweet bee venom pharmacopuncture(BVA) and sweet bee venom pharmacopuncture+ low level laser acupuncture(BVA+LLA) groups experienced a more significant effect when compared with the control group. Conclusions : These results suggest that Sweet Bee Venom Pharmacopuncture and low level laser acupuncture at GB34 and GB39 have a significant anti-inflammatory effect on Freund's adjuvant arthritis in rats.

• Journal of Life Science
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• v.26 no.1
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• pp.91-100
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• 2016

Angiogenesis is essential for the pathophysiological processes of embryogenesis, tissue growth, diabetic retinopathy, psoriasis, wound healing, rheumatoid arthritis, cardiovascular diseases, and tumor growth. Inhibition of angiogenesis represents an attractive therapeutic approach for the treatment of angiogenic diseases such as cancer. However, uncontrolled angiogenesis is also necessary for tumor development and metastasis. Inhibition of vascular endothelial growth factor (VEGF) signaling, a critical factor in the induction of angiogenesis, cause robust and rapid changes in blood vessels of tumors and therefore VEGF constitutes a target for such anti-angiogenic therapy. Recently, since natural compounds pose significantly less risk of deleterious side effects than synthetic compounds, a great many natural resources have been assessed for useful substance for anti-angiogenic treatment. Here we evaluated the anti-angiogenic effects of a hot water extract of Scutellaria baicalensis (SBHWE) using in vitro assays and ex vivo animal experiments. Our results show that SBHWE dose-dependently abrogated vascular endothelial responses by inhibiting VEGF-stimulated migration and invasion as well as tube formation in a human umbilical vein endothelial cell (HUVEC) model, without cytotoxicity, as determined by a cell viability assay. Further study revealed that SBHWE prevented VEGF-induced neo-vascularization in a rat aortic ring sprouting model. Taken together, our findings reveal an anti-angiogenic activity of Scutellaria baicalensis and suggest that SBHWE is a novel candidate inhibitor of VEGF-induced angiogenesis.

• Journal of Life Science
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• v.24 no.3
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• pp.219-226
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• 2014

The immune system protects the body from bacterial infection and disease, as well as cancer that develops following the mutation of cells. Aging exerts adverse effects on the immune system, such as chronic inflammation, resulting in rheumatoid arthritis. The purpose of this study was to investigate the anti-inflammatory effectiveness of Scutellaria baicalensis, which contains baicalin. HPLC analysis showed that S. baicalensis hot water extracts (SBWE) contained 42.2 mg/g of baicalin. To evaluate the cytotoxicity of SBWE, an MTT assay was carried out in Raw264.7 cells. No cytotoxicity was observed below 160 ${\mu}g/ml$ of SBWE. SBWE at 40 ${\mu}g/ml$ reduced the amount of nitric oxide produced by macrophages stimulated with lipopolysaccharide by 40%. In addition, SBWE inhibited phagocytosis stimulated with zymosan. Furthermore, the content of tumor necrosis factor-alpha ($TNF-{\alpha}$) produced by the macrophages was decreased in the presence of SBWE in a dose-dependent manner. SBWE also inhibited the production of interleukin-1 beta ($IL-1{\beta}$) in a time course experiment. Moreover, treatment with 20 ${\mu}g/ml$ of SBWE remarkably decreased the expression level of cyclooxynase-2. The results provide evidence that SBWE may exert an anti-inflammatory effect through modulation of the immune system.

• Journal of Acupuncture Research
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• v.22 no.2
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• pp.93-101
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• 2005

Objective: We have evaluated UDHA into the joint for its effectiveness on immune responses to CII in the rat CIA. In an attempt to gain further insight into the mode of action of UDHA, we also investigated the effects of UDHA on the incidence and development of arthritis in rat CIA with 2 different regimens: (1) started prior to a primary immunization, (2) started on the day of a primary immunization. Methods : Male rats were immunized with an emulsion of $200\;{\mu}g/100g$ of CII and complete Freund's adjuvant (CFA). The rats were then given intraperitoneal(i.p) stimulation of Ulmus davidiana Planch herbal acupuncture(UDHA) or saline during the experiment. Lymph node cells were obtained from rats 14 days after immunization and cultured in vitro with CII. When compared with rats treated with saline as control, UDHA at doses of more than $20\;{\mu}g/100\;g$ rat once a day for 7 days inhibited the ability of inguinal lymph node cells to produce T cell cytokines interleukin-$1{\beta}$, tumor necrosis $factor-{\alpha}$ $(TNF-{\alpha})$. When rats were injected intraperitoneally with SRBC, hemaglutination titers in UD-treated and control rats did not differ significantly when low doses of UD was given to rats. However, i.p injection of UD at doses of more than $10\;{\mu}g/100\;g/day$ for 7 days slightly suppressed antibody production. Results : The present results show that treatment with UDHA can inhibit the onset and development of arthritis and the immune responses to collagen. Conclusion: Therapeutic i.p injection with UD affect the clinical course of the disease and the immune responses to CII.

• International Journal of Oral Biology
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• v.36 no.4
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• pp.173-178
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• 2011

Tumor necrosis factor alpha ($TNF{\alpha}$) is a multifunctional cytokine that is elevated in inflammatory diseases such as atherosclerosis, diabetes and rheumatoid arthritis. Recent evidence has suggested that ${\beta}2$ adrenergic receptor (${\beta}2AR$) activation in osteoblasts suppresses osteogenic activity. In the present study, we explored whether $TNF{\alpha}$ modulates ${\beta}AR$ expression in osteoblastic cells and whether this regulation is associated with the inhibition of osteoblast differentiation by $TNF{\alpha}$. In the experiments, we used C2C12 cells, MC3T3-E1 cells and primary cultured mouse bone marrow stromal cells. Among the three subtypes of ${\beta}AR$, ${\beta}2$ and ${\beta}3AR$ were found in our analysis to be upregulated by $TNF{\alpha}$. Moreover, isoproterenol-induced cAMP production was observed to be significantly enhanced in $TNF{\alpha}$-primed C2C12 cells, indicating that $TNF{\alpha}$ enhances ${\beta}2AR$ signaling in osteoblasts. $TNF{\alpha}$ was further found in C2C12 cells to suppress bone morphogenetic protein 2-induced alkaline phosphatase (ALP) activity and the expression of osteogenic marker genes including Runx2, ALP and osteocalcin. Propranolol, a ${\beta}2AR$ antagonist, attenuated this $TNF{\alpha}$ suppression of osteogenic differentiation. $TNF{\alpha}$ increased the expression of receptor activator of NF-${\kappa}B$ ligand (RANKL), an essential osteoclastogenic factor, in C2C12 cells which was again blocked by propranolol. In summary, our data show that $TNF{\alpha}$ increases ${\beta}2AR$ expression in osteoblasts and that a blockade of ${\beta}2AR$ attenuates the suppression of osteogenic differentiation and stimulation of RANKL expression by $TNF{\alpha}$. These findings imply that a crosstalk between $TNF{\alpha}$ and ${\beta}2AR$ signaling pathways might occur in osteoblasts to modulate their function.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2019.10a
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• pp.92-92
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• 2019

Excessive or chronic inflammation contributes to the pathogenesis of many inflammatory diseases such as sepsis, rheumatoid arthritis, and ulcerative colitis. Hibiscus syriacus L. has been used as a medicinal plant in many Asian countries, even though its anti-inflammatory activity has been unclear. Therefore, we investigated the anti-inflammatory effect of anthocyanin fractions from the H. syriacus L. varieties Pulsae (PS) on the lipopolysaccharide (LPS)-induced expression of proinflammatory mediators and cytokines in RAW264.7 macrophages. PS suppressed LPS-induced nitric oxide (NO) and prostaglandin $E_2$ ($PGE_2$) secretion concomitant with downregulation of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) expression. Furthermore, PS inhibited the production of proinflammatory cytokines such as tumor necrosis factor-alpha ($TNF-{\alpha}$), interleukin-6 (IL-6), and IL-12 in LPS-stimulated RAW264.7 macrophages. Further study showed that PS significantly decreased LPS-induced nuclear translocation of the nuclear $factor-{\kappa}B$ ($NF-{\kappa}B$) subunits, p65 and p50. Molecular docking data showed that many anthocyanins from PS fit into the hydrophobic pocket of MD2 and bound to Toll-like receptor 4 (TLR4), indicating that PS inhibits the TLR4-MD2-mediated inflammatory signaling pathway. Especially, apigenin-7-O-glucoside most powerfully bound to MD2 and TLR4 through LYS122, LYS122, and SER127 at a distance of $2.205{\AA}$, $3.098{\AA}$, and $2.844{\AA}$ and SER441 at a distance of $2.873{\AA}$ (docking score: -8.4) through hydrogen bonding, respectively. Additionally, PS inhibited LPS-induced TLR4 dimerization/expression on the cell surface, which consequently decreased MyD88 recruitment and IRAK4 phosphorylation. PS completely blocked LPS-mediated mortality in zebrafish larvae by diminishing the recruitment of neutrophil and macrophages accompanied by low levels of proinflammatory cytokines. Taken together, our results indicate that PS attenuates LPS-mediated inflammation in both in vitro and in vivo by blocking the TLR4/MD2-MyD88/IRAK4-$NF-{\kappa}B$ axis. Therefore, PS might be used as a novel modulatory candidate for effective treatment of LPS-mediated inflammatory diseases.

• Journal of Life Science
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• v.33 no.9
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• pp.703-712
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• 2023

Angiogenesis, the formation of blood vessels from pre-existing vessels, is a multistep process regulated by modulators of angiogenesis. It is essential for various physiological processes, such as embryonic development, chronic inflammation, and wound repair. Dysregulation of angiogenesis causes many diseases, such as cancer, autoimmune diseases, rheumatoid arthritis, cardiovascular disease, and delayed wound healing. However, the number of effective anti-angiogenic drugs is limited. Recent research has focused on identifying potential drug candidates from natural sources. For example, marine natural products have been shown to have anti-cancer, anti-oxidant, anti-inflammatory, antiviral, and wound-healing effects. Thus, this study aimed to describe the angiogenesis inhibitory effect of Hizikia fusiforms (brown algae) extract. The hexane extract of H. fusiformis has shown inhibitory effects on in vitro angiogenesis assays, such as cell migration, invasion, and tube formation in human umbilical vein endothelial cells (HUVECs). The hexane extract of H. fusiformis (HFH) inhibited in vivo angiogenesis in a mouse Matrigel gel plug assay. In addition, the protein expression of vascular endothelial growth factor (VEGF), mitogen-activated protein kinase (MAPK)/extracellular signal kinase, and AKT serine/threonine kinase 1 decreased following treatment with H. fusiformis extracts. Our results demonstrated that the hexane extract of H. fusiformis (HFH) inhibits angiogenesis in vitro and in vivo.

• Journal of Life Science
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• v.34 no.6
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• pp.399-407
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• 2024

Angiogenesis is the process by which new blood vessels form from existing blood vessels. This phenomenon occurs during growth, healing, and menstrual cycle changes. Angiogenesis is a complex and multifaceted process that is important for the continued growth of primary tumors, metastasis promotion, the support of metastatic tumors, and cancer progression. Impaired angiogenesis can lead to cancer, autoimmune diseases, rheumatoid arthritis, cardiovascular disease, and delayed wound healing. Currently, there are only a handful of effective antiangiogenic drugs. Recent studies have shown that natural marine products exhibit antiangiogenic effects. In a previous study, we reported that the hexane extract of H. fusiformis (HFH) could inhibit the development of new blood vessels both in vitro and in vivo. The aim of this study was to describe the inhibitory effect of chloroform extracts of H. fusiformis on angiogenesis. To investigate how chloroform extract prevents blood vessel growth, we examined its effects on HUVEC, including cell migration, invasion, and tube formation. In a mouse Matrigel plug assay, H. fusiformis chloroform extract (HFC) also inhibited angiogenesis in vivo. Certain proteins associated with blood vessel growth were reduced after HFC treatment. These proteins include vascular endothelial growth factor (VEGF), mitogen-activated protein kinase (MAPK)/extracellular signal transduction kinase, and serine/threonine kinase 1 (AKT). These studies have shown that the chloroform extract of H. fusiformis can inhibit blood vessel growth both in vitro and in vivo.