• The Journal of Korean Obstetrics and Gynecology
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• v.23 no.2
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• pp.71-84
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• 2010

Purpose: In the theory of traditional medicine, Glenditsia spina(GS) can resolve carbuncle, relive swelling, dispel wind and destroy parasites. This study was designed to investigate the effects of GS on gene expression of ovarian tissue in polycystic ovary syndrome(PCOS) rats. Methods: In this experiment, female rats injected with a single dose of 2 mg estradiol valerate(EV) and GS was given for 5 weeks. The genetic profile for the effects on ovarian tissue in PCOS rats was measured using microarray technique, and the functional analysis on these genes was conducted. Results: 985 genes were increased in control and restored to normal level in GS group. (B), 733 genes were decreased in control group and restored to normal level in GS group. (F). Metabolic pathways related in B group genes were Graft-versus-host disease, Allograft rejection, Autoimmune thyroid disease, Cytokine-cytokine receptor interaction, Small cell lung cancer, Type I diabetes mellitus. Metabolic pathways related in F group genes were Antigen processing and present, Adipocytokine signalling pathway, Focal adhesion, ECM-receptor interaction, Pancreatic cancer, Notch signalling pathway, Tight junction. The network of total protein interactions was measured using cytoscape program, and some key molecules, such as c-Fos, c-Myc, ABL1 related in B group, MAPK8, RASA1, CALR related in F group that can be used for elucidation of therapeutical mechanism of medicine in future were identified. Conclusion: These results suggest possibility of GS as anti-cancer and anti-hyperplasia drug in PCOS. In addition, the present author also suggests that related mechanisms are involved in suppression of proto-oncogene such as c-Fos, c-Myc and ABL1, and in regulation of cell cycle such as RASA1.

• The Journal of Korean Obstetrics and Gynecology
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• v.25 no.2
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• pp.1-11
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• 2012

Objectives: This study was conducted to evaluate the inhibitory effect of Melia Fructus extract on osteoclast differentiation. Methods: MTT-assay was performed to estimate cytotoxicity of Melia Fructus extract in BMMs stimulated with M-CSF. TRAP staining, TRAP activity and Real-time PCR were performed to know the inhibitory effect on osteoclast differentiation. Actin ring formation were analysed to observe the effect of Melia Fructus extract. Results: Melia Fructus extract decreased the number of TRAP positive cells and the expression of NFATc1 gene, c-Fos gene, TRAP and OSCAR in BMMs stimulated with RANKL. Melia Fructus extract has no cytotoxicity at the concentration used in this study. Melia Fructus extract restrained the formation of actin ring. Melia Fructus inhibited NF-${\kappa}B$ activity by inducing degradation of p-$IkB{\alpha}$. Conclusions: Melia Fructus has the inhibitory effect of osteocalst differentiation and bone resorption. Further studies are needed to treat osteoporosis by herbal medicine containing Melia Fructus.

• The Journal of Korean Obstetrics and Gynecology
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• v.27 no.1
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• pp.17-27
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• 2014

Objectives: This study was conducted to evaluate the inhibitory effect of polygoni cuspidati radix (PCR) extract on osteoclast differentiation. Methods: MTT-assay was performed to estimate cytotoxicity of PCR extract in BMMs stimulated with RANKL. Tartrate resistant acid phosphatase (TRAP) staining, TRAP activity and RT-PCR were performed to know the inhibitory effect on osteoclast differentiation. actin ring formation were analysed to observe the effect of PCR extract. Results: PCR decreased the number of TRAP positive cells and TRAP activities in BMMs stimulated with RANKL and M-CSF. PCR restrained the formation of actin ring. PCR down regulated the induction of NFATc1, c-Fos, TRAP and OSCAR by RANKL. PCR inhibited NF-${\kappa}B$ activity by inducing degradation of $I{\kappa}B{\alpha}$. Conclusions: We suggest that PCR Extracts can be an effective therapeutic agent on osteoclast differentiation caused by diseases such as osteoporosis.

• Journal of Acupuncture Research
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• v.21 no.3
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• pp.145-167
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• 2004

Objective : Neuropathic pain can be caused by a partial peripheral nerve injury. This kind of pain is usually accompanied by spontaneous burning pain, allodynia and hyperalgesia. It is not clear that scolopendrid aqua-acupuncture can control neuropathic pain effectively. The purpose of this study is to examine if scolopendrid aqua-acupuncture may be effective to the neuropathic pain (mechanical allodynia, cold allodynia) in a rat model of neuropathic pain. Methods : To produce the model of neuropathic pain, under isoflurane 2.5% anesthesia, tibial nerve and sural nerve was resected. After the neuropathic surgery, the author examined if the animals exhibited the behavioral signs of allodynia. The allodynia was assessed by stimulating the medial malleolus with von Frey filament and acetone. Three weeks after the neuropathic surgery, scolopendrid aqua-acupuncture was injected at Hwando(GB30) one time a day for one week. After that the author examined the withdrawl response of neuropathic rats' legs by von Frey filament and acetone stimulation. And also the author examined c-fos in the midbrain central gray of neuropathic rats and the change of WBC count in the blood of neuropathic rats. Results & Conclusion : 1. The scolopendrid aqua-acupuncture injected at Hwando(GB30) decreased the withdrawl response of mechanical allodynia in SHA-1, SHA-2 and SAH-3 group as compared with control group. 2. The scolopendrid aqua-acupuncture injected at Hwando(GB30) decreased the withdrawl response of chemical allodynia(cold allodynia) in SHA-1, SHA-2 and SAH-3 group as compared with control group. 3. The scolopendrid aqua-acupuncture injected at Hwando(GB30) showed the significant difference between sham group and control group(p=0.01), sham and SHA-3 group(p=0.026), control group and SHA-1 group(p=0.01), control group and SHA-2 group(p=0.024) in the c-fos expression. 4. The scolopendrid aqua-acupuncture injected at Hwando(GB30) showed the significant difference between sham group and SHA-3 group(p=0.010), control group and SHA-3 group(p=0.006) in the WBC count.

• 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.

• The Korea Journal of Herbology
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• v.38 no.5
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• pp.9-19
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• 2023

Objectives : Osteoporosis is a systemic skeletal disorder characterized by reduced bone mineral density and increased risk of fractures. Bisphosphonates and selective estrogen receptors, which are bone resorption inhibitors that are currently widely used as osteoporosis treatments, show serious side effects when administered for a long time. Research on bone resorption inhibitors that complement the problems of existing treatments is needed. The purpose of this study was to investigate the effect of inhibiting osteoclast differentiation and activity on the tuberous root of Ampelopsis japonica (Thunb.) Makino (AM). Methods : After extracting AM using distilled water and ethanol, the inhibitory effects of the two solvents on osteoclast differentiation were compared using the RANKL-induced in vitro experimental model and the TRAP assay kit. The impact of AM on bone resorption was investigated through the pit formation assay, and its effect on F-actin formation was assessed through fluorescent staining. Additionally, protein and mRNA expression levels of osteoclast differentiation markers (NFATc1, c-Fos, TRAP and ATP6v0d2) and resorption markers (MMP-9, CTK, and CA2) were analyzed via western blot and RT-PCR. Results : AM treatment significantly decreased the number of TRAP-positive cells and pit formation area. Furthermore, AM suppressed both the protein and mRNA expression of NFATc1 and c-Fos, key transcription factors involved in osteoclast differentiation and it downregulated the expression of osteoclast-associated genes such as TRAP, CTK, MMP-9, CA2, and ATP6v0d2. Conclusions : These results suggest that AM can inhibit bone resorption and osteoclast differentiation, indicating its potential for use in the treatment and prevention of osteoporosis.

• YAKHAK HOEJI
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• v.57 no.5
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• pp.309-315
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• 2013

Cyanidin-3-glucoside (C3G), an anthocyanin, is one of the most widespread dietary flavonoids. We investigated the effects of C3G in PMA/ionomycin (PI)-induced RBL-2H3 cells. C3G inhibited the production of IL-4 and IL-13 and also decreased the level of mRNA in a dose-dependent manner. Furthermore, western blot analysis implied that C3G down-regulated the protein level of c-Jun, NF-ATc1 and NF-${\kappa}B$ but not c-Fos. Taken together, we suggest that C3G may have suppressive effects on Th2 cytokines and will be studied further to develop as functional foods that help alleviate allergy symptoms.

• Biomedical Science Letters
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• v.18 no.4
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• pp.369-376
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• 2012

Platycodon grandiflorum is a medicinal herb that is used to treat pulmonary and respiratory allergic disorders. The objective of this study was to investigate the protective effects of ethyl acetate extract of Platycodon grandiflorum (PGEA) against inflammation and to discern the molecular mechanism of PGEA in lipopolysaccharide (LPS)-induced signal pathways in RAW264.7 macrophage cells. PGEA suppressed the generation of nitric oxide (NO) and the expression of inducible NO synthase induced by LPS in RAW264.7 cells, and inhibited the release of pro-inflammatory cytokines induced by LPS in RAW264.7 cells. Western blot analysis showed that PGEA suppressed LPS-induced phosphorylation of p38 and c-Jun N-terminal kinase (JNK) but not extracellular signal-regulated kinase and $I{\kappa}-B{\alpha}$ degradation. Inactivation of JNK and p38 was effectively alleviated by PGEA, which subsequently affected the activation of c-Jun and c-Fos, which are the essential components of the activator protein-1 (AP-1) transcription complex. Taken together, the results indicate PGEA suppress the activation of p38, JNK, and AP-1, thereby inhibiting the generation of NO and pro-inflammatory cytokines, which affect the regulation of inflammation. PGEA may be useful for the treatment of various inflammatory diseases.

• BMB Reports
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• v.32 no.4
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• pp.379-384
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• 1999

Taxol, a natural product with significant anti-tumor activity, stabilizes microtubules and arrests cells in the G2/M phase of the cell cycle. It has been reported that taxol has additional effects on the cell such as an increase in tyrosine phosphorylation of proteins and activation of mitogen-activated protein (MAP) kinase. This phosphorylated kinase translocates into the nucleus and phosphorylates its substrate c-jun, c-fos, ATF2, and ATF3. The MAP kinase family is comprised of key regulatory proteins that control the cellular response to both proliferation and stress signals. First examination was cytotoxicity and apoptosis-induced concentration with paclitaxel in HeLa cell. A half-maximal inhibition of cell proliferation ($IC_{50}$) occurred at 13 nM paclitaxel. When DNA fragmentation was analyzed by agarose gel electrophoresis, a nucleosomal ladder became evident 24 h after a taxol (50 nM) addition to the cells. In addition, an apoptotic body was detected by electron microscopy. Taxol-treated cells were arrested at the S phase at 10 nM. Treatment of 50 nM taxol activated the extracellular signal-regulated protein kinase (ERK1), and a fraction of the activated MAP kinases entered the nucleus. It was also discovered that nucleus substrates c-jun was phosphorylated and activated in the cell. The activated ERK1 could subsequently translocate into the nucleus and phosphorylate its substrate c-jun as well. This study suggests that taxol-induced apoptosis might be related with signal transduction via MAP kinases.

• International Journal of Oral Biology
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• v.32 no.1
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• pp.1-5
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• 2007

Receptor activator of nuclear factor ${\kappa}B$ ligand (RANKL) induces osteoclast formation from hematopoietic cells via up-regulation of positive regulators, including $NF-{\kappa}B$, c-Fos, microphthalmia transcription factor (Mitf), PU.1, and nuclear factor of activated T cells (NFAT) c1. In addition to the positive regulation by these transcription factors, RANKL appears to regulate negative regulators such as MafB and inhibitors of differentiation (Ids). Ids and MafB are abundantly expressed in osteoclast precursors, bone marrowderived monocyte/macrophage lineage cells (BMMs). Expression levels of these genes are significantly reduced by RANKL during osteoclastogenesis. Overexpression of these genes in BMMs inhibits the formation of tartarate-resistant acid phosphatase (TRAP)-positive multinuclear osteoclasts by down-regulation of NFATc1 and osteoclast-associated receptor (OSCAR), which are important for osteoclast differentiation. Furthermore, reduced expression of these genes enhances osteoclastogenesis and increases expression of NFATc1 and OSCAR. Taken together, RANKL induces osteoclastogenesis via up-regulation of positive regulators as well as down-regulation of negative regulators.