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Matrix metalloproteinase-9 (MMP-9) plays an important role in the invasion and metastasis of cancer cells. The synthesis and secretion of MMP-9 can be stimulated by a variety of stimuli, including cytokines and phorbol 12-myristate 13-acetate (PMA), during various pathological processes, such as tumor invasion, atherosclerosis, inflammation, and rheumatoid arthritis, whereas MMP-2 is usually expressed constitutively. Delphinidin, an anthocyanidin present in pigmented fruits and vegetables, possesses potent antioxidant, anti-inflammatory, and antiangiogenic properties. In this study, we investigated the antiproliferative and antiinvasive effects of delphinidin on PMA-induced MMP-9 expression in MCF-7 human breast carcinoma cells using zymography, western blotting, reverse transcription-polymerase chain reaction, and Matrigel invasion assay. Delphinidin significantly suppressed PMA-induced MMP-9 protein expression in MCF-7 human breast carcinoma cells, and it also inhibited the MMP-9 gene transcriptional activity by blocking the activation of NFkappaB (NF-κB) through MAPK signaling pathways. Moreover, the Matrigel invasion assay showed that delphinidin reduces PMA-induced cancer cell invasion. These results suggest that delphinidin is a potential antimetastatic agent that suppresses PMA-induced cancer cell invasion through the specific inhibition of NF-κB-dependent MMP-9 gene expression.

To determine the potential function of Rhus javanicain Korean medicine, it was fermented with each strain of Lactobacillus spp. Each strain of Lactobacillus spp. was inoculated in lactobacilli MRS broth, and 5 ㎎/㎖ of methanol extract of Rhus javanicawas added. In mouse hippocampal HT22 cells, ethyl acetate extract of R. javanica fermented with L. brevis KCTC 3498 induced heme oxygenase-1 expression and showed a significant cytoprotective effect on glutamate-induced oxidative damage. The cytoprotective effect was related to the transcription of the nuclear factor E2-related factor2 (Nrf2), which is responsible for the induction of heme oxygenase-1 within the nucleus. The antimicrobial, antioxidant, and heme oxygenase-1 expression activities of fermented R. javanica were measured after extraction with ethyl acetate. R. javanica fermented with L. plantarum subsp. plantarum KCTC 3108, L. fermentum KCTC 3112, and L. brevis KCTC 3498 had higher antioxidant activity than nonfermented R. javanica.The fermented R. javanicawith L. plantarumsubsp. plantarumKCTC 3108, L. caseiKCTC 3109 after ethyl acetate extraction showed antibacterial activity against Bacillus subtilisPCI 219, Escherichia coli KCTC 1682, Shigella flexneri KCTC 2517, Vibrio parahaemolyticus KCTC 7471, and Pseudomonas aeruginosa KCTC 2004. An ethyl acetate extract of the fermented R. javanica with Lactobacillus brevis KCTC 3498 exhibited stronger antibacterial activity than a nonfermented one against strains of B. subtilis PCI 219, E. coli KCTC 1682, S. flexneri KCTC 2517, and V. parahaemolyticus KCTC 7471.

6,4'-Dihydroxy-7-methoxyflavanone (DMF) is a flavonoid isolated from Heartwood Dalbergia odorifera. It has been known that DMF has antioxidant, anti-inflammatory and neuroprotective effects. DMF, however, the efficacy of bone related diseases has not been reported. In this study, we determined DMF's efficacy on osteoclasts differentiation and function using in vitro bone marrow macrophage osteoclast differentiation culture system. DMF inhibited receptor activators of nuclear factor kappa-B ligand (RANKL) induced osteoclastogenesis dose dependently. In addition, DMF decreased osteoclast function through disruption of actin ring formation and consequently suppression of the pit-forming activity of mature osteoclasts. Mechanistically, DMF inhibited RANKL-induced expression of nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1 (NFATc1) and c-Fos via inhibition of mitogen activated protein kinases (MAPKs) pathway. Collectively, the inhibition of osteoclasts differentiation and function by DMF suggests that DMF can be a potential therapeutic molecule for osteoclastogenic bone diseases such osteoporosis, rheumatoid arthritis and periodontal diseases.

This study was performed to evaluate the effects of skullcap (Scutellaria baicalensis Georgi, SBG) on differentiation of RAW 264.7 cell into osteoclast-like cells and bone resorption of mature osteoclast to propose candidates for the prevention or treatment of osteoporosis. In the screening of 140 natural products, the selected SBG methanol extract dramatically reduced tartrate-resistant acid phosphatase (TRAP) activity to 21% at 10 μg/mL. The proliferation was evaluated using the MTT assay, and the survival rates of RAW 264.7 cells treated with 10–100 μg/mL extract were over 80% with most concentrations. The chloroform fraction from SBG (SBG-C) decreased TRAP activity. The SBG-C increased the expression of the pro-apoptotic protein Bax and reduced the expression of the anti-apoptotic protein Bcl-2. It also stimulated caspase-3 activity in osteoclasts. In addition, the actin rings were loose and fuzzy in the presence of these fractions. A resorption pit was formed by multinucleated osteoclastic cells, but was not observed in the presence of the SBG-C (10 μg/mL). In conclusion, we found SBG suppressed osteoclast differentiation and bone resorption. It also inhibited osteoclast survival. Therefore SBG is expected to be a natural source for the development of functional food and medical agents to prevent or treat osteoporosis.

The antioxidant activities of fermented red ginseng (FRG) were investigated in vitro and in vivo. The contents of total polyphenol and total flavonoid in FRG extracts were 17.01±2.00 μg/mg and 18.42±3.97 μg/mg, respectively. These extracts were capable of directly scavenging α, α-diphenyl-picrylhydrazyl free radicals. The antioxidative effects of the FRG extracts in streptozotocin (STZ)-induced diabetic rats were also investigated. The activities of plasma alanine transaminase, aspartate transaminase, and γ-glutamyltransferase were significantly decreased by extract administration as compared to an STZ control group. Hepatic glutathione content depleted by STZ treatment was significantly increased by treatment of the FRG extracts, but the elevation of lipid peroxide content induced by STZ was significantly decreased by the extracts. Activities of superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase decreased after STZ-treatment were recovered by the treatment of the FRG extracts. These results indicate that FRG extracts have antioxidative effets in STZ-induced diabetic rats.

The effects of inhaling three essential oils (lavender [Lavendular angustifolia], silver fir [Abies alba], and grapefruit [Citrus paradise]) against restraint stress were investigated in mice. Serum cortisol levels were significantly increased in the 1h-restraint group. Also, silver fir and grapefruit oils prevented the elevation of cortisol levels under experimental conditions. Inhalation of 10% lavender oil for 30 min before inducing stress significantly inhibited restraint-induced hypothermia. We also investigated the effects of restraint stress on triglycerides, total cholesterol, and high-density lipoprotein cholesterol. It was found that the concentration of triglycerides in the serum samples increased after restraint stress. Silver fir essential oil inhibited elevation of triglyceride levels. Taken all together, the correlation of herb essential oil inhalation against restraint stress in animals can partly be explained.

Osteoclasts, bone-resorbing multinucleated cells, are differentiated from hemopoietic progenitors of the monocyte/macrophage lineage. Bone resorption by osteoclasts is considered a potential therapeutic target to the treatment of erosive bone diseases, including osteoporosis, rheumatoid arthritis, and periodontitis. In the present study, we found that alisol-B, a phyto-steroid from Alisma orientale Juzepczuk, exhibited inhibitory effects on osteoclastogenesis both in vitro and in vivo. Although RT-PCR analysis showed that alisol-B did not affect the 1alpha,25(OH)(2)D(3)-induced expressions of RANKL, OPG and M-CSF mRNAs in osteoblasts, addition of alisol-B to co-cultures of mouse bone marrow cells and primary osteoblasts with 10(-8)M 1alpha,25(OH)(2)D(3) caused significant inhibition of osteoclastogenesis. We further examined the direct effects of alisol-B on osteoclast precursors. Alisol-B strongly inhibited RANKL-induced osteoclast formation when added during the early stage of cultures, suggesting that alisol-B acts on osteoclast precursors to inhibit RANKL/RANK signaling. Among the RANK signaling pathways, alisol-B inhibited the phosphorylation of JNK, which are upregulated in response to RANKL in bone marrow macrophages, alisol-B also inhibited RANKL-induced expression of NFATc1 and c-Fos, which are key transcription factors for osteoclastogenesis. In addition, alisol-B suppressed the pit-forming activity and disrupted the actin ring formation of mature osteoclasts. In a hypercalcemic mouse model induced by 2-methylene-19-nor-(20S)-1alpha,25(OH)(2)D(3) (2MD), an analog of 1alpha,25(OH)(2)D(3), administration of alisol-B significantly suppressed 2MD-induced hypercalcemia as resulting from the inhibition of osteoclastogenesis. Taken together, these findings suggest that alisol-B may be a potential novel therapeutic molecule for bone disorders by targeting the differentiation of osteoclasts as well as their functions.

The essential oil of tea tree (Melaleuca alternifolia) is widely used in traditional Australian medicine for skin lesions and infected injuries. In the present study, we investigated the chemical composition, cytotoxicity and its biological activities. The composition of the oil was analyzed by GC-MS. β-Terpinene (20.87%), α-pinene (17.60%), p-cymene (11.23%), 3-carene (10.40%), trans-anethole (8.47%) and limonene (4.65%) were the major components in the oil. The results tested by MTT assay indicated that the oil showed no cytotoxic effect, at concentrations up to 5%, for less than 3h. The antiradical capacity was evaluated by measuring the scavenging activity of the essential oil on the 2,20-diphenylpicrylhydrazyl (DPPH) and 2,2'-azino-bis 3-ethyl benzothiazoline-6-sulfonic acid (ABTS) radicals. The oil was able to reduce the both radicals dose-dependently, and the concentration required for 50% reduction (RC??) against ABTS radicals (1.6±0.02%) was slightly lower than DPPH radicals (2.6±0.29%). The direct contact and vapor-phase antibacterial activity of the oil were also evaluated using disc diffusion method against Staphylococcus aureus, Streptococcus mutans, Listeria monocytogenes, Acinetobacter baumannii, Escherichia coli, and Vibrio parahaemolyticus. All the Gram-negative bacterial strains tested showed more sensibility to the oil than the Gram-positive strains when compare to the effect of gentamycin. On the other hand, the vapor phase of the essential oil against S. aureus exhibited strongest inhibitory effect.

A diet rich in polyphenols has previously been shown to be associated with a lower risk for cardiovascular dis- ease. Specifically, inhibition of platelet hyperactivation by polyphenols decreases platelet-dependent thrombosis, reducing the risk for cardiovascular disease. However, whether polyphenols in Salvia miltiorrhiza Bunge (SMB) affect platelet functions has not been clearly determined. Here, we investigated the effects of methanol and ethyl acetate (EtOAc) ex- tracts from SMB on free radical scavenging activities, and platelet aggregation and adhesion. We found that the EtOAc fraction was the most effective at scavenging 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azinobis(3- ethylbenzothiazoline-6-sulfonic acid) (ABTS) free radicals (concentration for 50% reduction, RC50 = 2.4 ± 1.5 and 27.9 ± 1.4 μg/mL, respectively), and that, especially for DPPH radicals, the EtOAc fraction showed better scavenging activity than butylated hydroxyanisole (BHA, RC50 = 5.5 ± 0.1 μg/mL). Measurements with a turbidimetric aggregometer revealed that the EtOAc fraction was the most potent inhibitor of ADP- and collagen-induced rat platelet aggregation. In addition, the methanol and EtOAc fraction dose-dependently inhibited thrombin-stimulated platelet adhesion to collagen or fibrino- gen. Collectively, these results suggest that the polyphenol-rich EtOAc fraction from SMB can reduce platelet hyperacti- vation by scavenging free radicals. Thus, the EtOAc fraction of SMB is a potential source of inhibitors of platelet- dependent thrombosis.

In this study we evaluated the method to develop red ginseng oil containing high content of phytochemicals by enzymes treatment. To select the optimum extraction process of red ginseng with oils, the antioxidant activities of red ginseng using various enzymes were measured. Red ginseng after 0.5% cellulase treatment for 1 hr at had higher antioxidant activity than the other conditions. We found that red ginseng/soybean oil extracted for 15 days at after 0.5% cellulase treatment increased DPPH radical scavenger activity and decreased the TBA and POV values. However, red ginseng/olive oil had little functional activities compare to the red ginseng/soybean 0il. We also analyzed vitamin A and E by HPLC and found that vitamin E was increased by 0.5% cellulase treatment in the oil. This is the first report that red ginseng oil extracted by enzyme treatment has various beneficial effects.

Lupeol is a lupane-type triterpene isolated from Sorbus commixta, an oriental medicine used to treat arthritis and inflammatory diseases. However, the antiosteoporotic effects of S. commixta or any of its constituents have not been studied yet. In the present study, we have examined the effect of lupeol (a major active triterpenoid isolated from S. commixta) on osteoclastogenesis and sought to elucidate its underlying molecular mechanisms. We evaluated whether lupeol antagonized osteoclast differentiation and bone resorption. Lupeol markedly inhibited osteoclast differentiation and bone resorption activity through its effects on MAP kinases and transcription factors (NF-κB, NFATc1, and c-Fos) downstream of the osteoclast differentiation factor receptor RANK. Furthermore, in vivo efficacy of lupeol was confirmed by using an animal model of hypercalcemic mediated bone loss. Taken together, lupeol showed strong inhibitory effects on osteoclastogenesis. Supplementation with S. commixta and lupeol could be beneficial for bone health or osteoclast-related diseases such as osteoporosis, Paget's disease, osteolysis associated with periodontal disease, and multiple myeloma.

This study was carried out to investigate the effect of Spatholobus suberectus Dunn (SS) on the protection of chondral defect and inhibition of osteoclastogenesis. To examine these effects, we measured the matrix metalloproteinase (MMP) levels in SW1353 chondrosarcoma cells and performed tartrate-resistant acid phosphatase (TRAP) staining in bone marrow macrophage (BMM)-derived osteoclasts. To investigate the anti-osteoarthritis (OA) effects, we assessed TNF-α-induced MMP-1, -3, -9 and tissue inhibitors of matrix metalloproteinase (TIMP) expression levels in SW1353 cells. We observed that SS extract significantly inhibited MMP and TIMP expression in SW1353 cells. Also, SS extract inhibited the receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation. These results suggest that SS extract may have a potential in the treatment of bone loss and chondral defect by suppressing osteoclast differentiation and decreasing the expression of OA factors. Therefore, clarification of the mechanism of the action of SS extract and its active components is needed.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the Editor. The authors have found multiple errors with the submission including but not limited to the incorporation of a figure (figure 6C) previously published in the Korean Journal of Pharmacognosy 2014. Apr, 45(2):161–167, http://kpubs.org/article/articleMain.kpubs?articleANo=HKSOBF_2014_v45n2_161. The authors extend an apology to readers and editors for this matter.

Dalbergia odorifera T. Chen (Leguminosae) has traditionally been used as an ingredient in East Asian medicines to treat various diseases. In the present study, 4,2′,5′-trihydroxy-4′-methoxychalcone (TMC), a biologically active chalcone isolated from the heartwood of D. odorifera, inhibited cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression, leading to a reduction in COX-2-induced prostaglandin E2 (PGE2) and iNOS-induced nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated murine peritoneal macrophages. Furthermore, TMC suppressed tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) production, and the phosphorylation and degradation of IκB-α as well as the LPS-stimulated nuclear translocation of p65 in macrophages. The present study also demonstrated that TMC induced heme oxygenase-1 (HO-1) expression through the nuclear translocation of nuclear factor E2-related factor 2 (Nrf2) in macrophages. The effects of TMC on LPS-induced NO, PGE2, tumor necrosis factor (TNF)-α, and interleukin (IL)-1β production were partially reversed by the HO inhibitor tin protoporphyrin (SnPP). These results suggest that TMC inhibits pro-inflammatory mediators by inducing the expression of anti-inflammatory HO-1 via the Nrf2 pathway.

Jujube (Ziziphus jujube) was analyzed at eight stages of ripeness (S1–8) for protein, by HPLC and mass spectroscopy for free amino acids and flavonoids, and by colorimetry for total flavonoids and antioxidative activity. The ripe fruit had lower levels of protein, flavonoids, and antioxidative activity than that of the unripe fruit. Free amino acids levels peaked at S5, due mainly to an increase in free asparagine. Extracts were also tested against four cell lines using the MTT cell viability assay. All growth stages dose-dependently inhibited HeLa cervical cancer cells, whereas the inhibition of Hel299 normal lung and A549 lung cancer cells decreased as the fruit matured and was well correlated with the flavonoid content and antioxidative activity. Chang normal liver cells were inhibited by only the S5 extract. U937 lymphoma cells were unaffected by the extracts. These results show the effect of fruit maturity on nutritional and health-promoting components.

Atherosclerosis is a chronic and progressive inflammatory disease. Novel anti-inflammatory therapies may have promise as treatment strategies for cardiovascular risk reduction. Rosemary (Rosemarinus officinalis L.) has been used in folk medicine to treat headaches, epilepsy, poor circulation, and many other ailments. It was found that rosemary could act as a stimulant and mild analgesic and could reduce inflammation. However, the mechanisms underlying the anti-inflammatory and antiatherosclerotic effects of rosemary need more study. This study investigated effects of the rosemary components, carnosic acid (CA), and carnosol (CAR), on cell migration. Monocyte chemoattractant protein-1 (MCP-1) and matrix metalloproteinase-9 (MMP-9) were determined by Western blot and gelatin zymography, respectively, in RAW 264.7 macrophages and vascular smooth muscle cells (VSMCs). VSMC migration was assessed by a Matrigel migration assay. Active compounds of rosemary extracts were also analyzed using a reversed-phase high-performance liquid chromatography. MMP-9 and MCP-1 activities were markedly diminished with methanol extract (RM), n-hexane fraction (RH), and CA in RAW 264.7 cells. RM, RH, CA, and CAR suppressed tumor necrosis factor-alpha-induced VSMC migration by inhibiting MMP-9 expression. Chromatograms of RM- and RH-containing CA and CAR revealed higher CA contents of RM (9.4%, 93.85 μg/mg dry wt.) and, especially, RH (18.4%, 184.00 μg/mg dry wt.), which were appreciably elevated compared with the similar CAR content in RM and RH (3.7%, 37.30 μg/mg dry wt.; and 2.5%, 25.05 μg/mg dry wt., respectively). Rosemary, especially its CA component, has potential antiatherosclerosis effects related to cell migration.

The essential oil of silver fir (Abies alba) is known to help respiratory system and have easing and soothing effect for muscle. In the present study, we investigated the chemical composition, cytotoxicity and its biological activities of silver fir (Abies alba) essential oil. The composition of the oil was analyzed by GC-MS and bornyl acetate (30.31%), camphene (19.81%), 3-carene (13.85%), tricyclene (12.90%), dl-limonene (7.50%), alpha-pinene (2.87%), caryophyllene (2.18%), beta-phellandrene (2.13%), borneol (1.74%), bicyclo[2.2.1]hept-2-ene,2,3-dimethyl (1.64%) and alpha-terpinene (1.24%) were the major components in the oil. The results tested by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay indicated that the oil showed no cytotoxic effect, at concentrations of 1 and 5%, for as long as 24 and 3 h, respectively. The antiradical capacity was evaluated by measuring the scavenging activity of the essential oil on the 2,20-diphenylpicrylhydrazyl (DPPH) and 2,2'-azino-bis 3-ethyl benzothiazoline-6-sulfonic acid (ABTS) radicals. The oil was able to reduce the both radicals dose-dependently, and the concentration required for 50% reduction (RC(50)) against DPPH radicals (2.7 +/- 0.63%) was lower than ABTS radicals (8.5 +/- 0.27%). The antibacterial activity of the oil was also evaluated using disc diffusion method against Staphylococcus aureus, Streptococcus mutans, Listeria monocytogenes, Acinetobacter baumannii, Escherichia coli, and Vibrio parahaemolyticcus. The oil exhibited no antibacterial activity against all the bacterial strains tested except S. aureus of mild activity.

Sesquiterpene-quinone is a class of secondary metabolites frequently encountered from marine sponge. The present study was designed to examine the anti-inflammatory action of sponge-derived dactyloquinone B (DQB) and cyclospongiaquinone-1 (CSQ1) mixture using lipopolysaccharide (LPS)-induced inflammatory responses. We measured the production of nitric oxide (NO), tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) and expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein. TNF-α, IL-1β, and IL-6 production, which increased by treatment with LPS, were significantly inhibited by DQB and CSQ1 mixture. It also decreased the production of NO production, and iNOS and COX-2 expression. Furthermore, it reduced 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced ear edema of ICR mice. These results demonstrate that sesquiterpene-quinone, DQB and CSQ1 mixture, might serve as a chemical pipeline for the development of anti-inflammatory agent. Keywords - Dactyloquinone B, Cyclospongiaquinone-1, Anti-inflammatory effect, Ear edema model