• Biomolecules & Therapeutics
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• v.23 no.2
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• pp.128-133
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• 2015

Although coffee is known to have antioxidant, anti-inflammatory, and antitumor properties, there have been few reports about the effect and mechanism of coffee compounds in colorectal cancer. Heat shock proteins (HSPs) are molecular chaperones that prevent cell death. Their expression is significantly elevated in many tumors and is accompanied by increased cell proliferation, metastasis and poor response to chemotherapy. In this study, we investigated the cytotoxicity of four bioactive compounds in coffee, namely, caffeine, caffeic acid, chlorogenic acid, and kahweol, in HT-29 human colon adenocarcinoma cells. Only kahweol showed significant cytotoxicity. Specifically, kahweol increased the expression of caspase-3, a pro-apoptotic factor, and decreased the expression of anti-apoptotic factors, such as Bcl-2 and phosphorylated Akt. In addition, kahweol significantly attenuated the expression of HSP70. Inhibition of HSP70 activity with triptolide increased kahweol-induced cytotoxicity. In contrast, overexpression of HSP70 significantly reduced kahweol-induced cell death. Taken together, these results demonstrate that kahweol inhibits colorectal tumor cell growth by promoting apoptosis and suppressing HSP70 expression.

• Biomolecules & Therapeutics
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• v.23 no.2
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• pp.119-127
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• 2015

Chalcones (1,3-diaryl-2-propen-1-ones), a subfamily of flavonoid, are widely known to possess potent anti-inflammatory and anti-oxidant properties. In this study, we investigated the effect of 3-(4-Hydroxyphenyl)-1-(thio3-(4-Hydroxyphenyl phen-2-yl)prop-2-en-1-one (TI-I-175), a synthetic chalcone derivative, on endotoxin-induced expression of monocyte chemoattractant protein-1 (MCP-1), one of the key chemokines that regulates migration and infiltration of immune cells, and its potential mechanisms. TI-I-175 potently inhibited MCP-1 mRNA expression stimulated by lipopolysaccharide (LPS) in RAW 264.7 macrophages without significant effect on cell viability. Treatment of cells with TI-I-175 markedly prevented LPS-induced transcriptional activation of activator protein-1 (AP-1) as measured by luciferase reporter assay, while nuclear factor-${\kappa}B$ (NF-${\kappa}B$) activity was not inhibited by TI-I-175, implying that TI-I-175 suppressed MCP-1 expression probably via regulation of AP-1. In addition, TI-I-175 treatment significantly inhibited LPS-induced Akt phosphorylation and led to a significant decrease in reactive oxygen species (ROS) production by LPS, which act as up-stream signaling events required for AP-1 activation in RAW 264.7 macrophages. Taken together, these results indicate that TI-I-175 suppresses MCP-1 gene expression in LPS-stimulated RAW 264.7 macrophages via suppression of ROS production and Akt activation.

• Journal of Pharmaceutical Investigation
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• v.41 no.4
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• pp.227-232
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• 2011

Alnus japonica has been known to exert antioxidative, anti-inflammatory, anti-cancer and immune response inhibitory effects. The aim of this study was to figure out the characteristics of extracts obtained with different extraction solvent such as water, 100% ethanol, 70% ethanol or 70% methanol because characteristic components such as oregonin and hirsutanone extracted from Alnus japonica might be essential for the biological activity. For this purpose, oregonin and hirsutanon of four extracts, index ingredient of Alnus japonica, were analyzed with HPLC and physicochemical studies such as SEM, particle size and zeta potential were conducted. In cell cytotoxicity study, extract of water showed the highest cytotoxicity among four extracts. In case of oregonin, 70% MeOH and water extracts showed high contents and in case of hirsutanone, all extracts showed similar contents except 70% EtOH extracts. The extract of 70% MeOH from Alnus japonica for both oregonin and hirsutanone appeared to have the highest content. Both oregonin and hirsutanone extracted from Alnus japonica using 70% methanol showed stability in pH 1.2.

• BMB Reports
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• v.39 no.2
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• pp.171-177
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• 2006

Nonsteroidal anti-inflammatory drugs such as indomethacin (IN) can exert anti-colorectal cancer (CRC) activity through cyclooxygenase independent mechanism, but the exactly biological mechanism is not completely known. Here we use proteomic tools to investigate the molecular mechanism of this action. First, nude mice bearing tumors derived from subcutaneous injection with human CRC cell line HCT116 were randomly allocated to groups treated with or without indomethacin. Later, tumor lumps were incised and then total proteins extracted. After separated with two-dimensional electrophoresis, thirty-one differently expressed spots were found between IN-treated and non-IN-treated groups, of which 25 spots decreased and 6 spots increased in abundance in IN-treated group. Through matrix-assisted laser desorption ionization time of flight mass spectrometry and then NCBInr and SWISS-PROT databases searching, 12 protein spots were finally identified including galectin-1, annexin A1, annexin IV, trancription factor BTF3A, calreticulin. Most of the identified proteins are correlated with tumor's biological prosperities of proliferation, invasion, apoptosis and immunity, or take part in cell's signal transduction. From above we thought that indomethacin can exert its effect on colorectal cancer through regulating several proteins' expression directly or indirectly. Further study of these proteins may be helpful in founding new targets of drugs for cancer chemotherapy.

• Toxicological Research
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• v.17
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• pp.271-280
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• 2001

We report on the applicability oj a method recently developed in our laboratory for measuring the antioxidant potential of isolated chemicals and extracts derived from natural products. Peroxyl radicals generated by thermal homolysis of 2,2'-azobis-amidinopropane (ABAP) oxidize $\alpha$-keto-${\gamma}$-methiolbutyric acid (KMBA) to ethylene, which is monitored by gas chromatography. Inhibition of ethylene formation in the presence of antioxidants that compete with KMBA for peroxyl radicals is the basis of the Total Oxyradical Scavenging Capacity Assay (TOSCA; Winston et al., 1998). Antioxidative activities of water-soluble extracts of American green tea, the anti-hepatotoxic flavonolignan from milk thistle (Silybum marianum) silybin, Ginkgo biloba extract EGb 761, and a series of naturally occuring sesquiterpene lactones (all ger-macranolides found in in fungi, liverworts, and plants) were studied. The specific TOSC value per $\mu$M silybin was 5.2, which is essentially comparable to that of Trolo $x^{ⓡ}$, a water-soluble vitamine E analog. Tea and Ginkgo extracts exhibited potent peroxyl radical scavenging capacity with values, respectively of =1700 and 1000 $\mu$mols Trolo $x^{ⓡ}$ equivalent per gram dry matter. The known anti-inflammatory activity of some germacranolides prompted study of their antioxidant capacity. None of the lactones exhibited antioxidant capacity toward peroxyl radicals comparable to Trolo $x^{ⓡ}$; costunilide, the most lipophilic, had a TOSC value = to glutathione. The potential role of peroxyl radicals in lipidperoxidation, other cellular damage, and var-ious disease states suggest a possible preventive role for silybin, green tea and Ginkgo biloba in oxidative stress caused by these free radical species.ecies.

• Toxicological Research
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• v.22 no.3
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• pp.229-235
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• 2006

Opuntia humifusa is a member of the Cactaceae family. In the present study, the antioxidant, nitric oxide(NO) inhibitory activities and potential irritation response of the fermented Opuntia humifusa cladodes(FOH) were investigated for cosmetic use. Antioxidant activities were tested using 1,1-diphenyl-2-picrylhydrazyl(DPPH) and xanthine oxidase assay, we found that FOH could scavenge DPPH free radicals and inhibit xanthine oxidase activity in a dose dependent manner, with $IC_{50}$ of 2599.46${\mu}g/ml$ and 721.38${\mu}g/ml$, respectively. To investigate the possible anti-inflammatory effects of FOH, RAW 264.7 macrophages were pretreated with FOH($0{\sim}400{\mu}g/ml$) for 30 min and then treated with LPS for 24 h. We found that cell number did not vary significantly with the treatment of FOH, and FOH did not show any inhibitory effects on LPS-induced NO production. After application of FOH to rabbits for skin and eye irritation test, the experimental sites did not show any response compared to the control. FOH were considered to be a non-irritant to the skin and eye. Based on the above information, we suggest that FOH can be considered to be a non-irritant base cosmetic material for safely use.

• The Korean Journal of Physiology and Pharmacology
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• v.20 no.3
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• pp.237-243
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• 2016

Oleanolic acid (OA) has a wide variety of bioactivities such as hepatoprotective, anti-inflammatory and anti-cancer activity and is used for medicinal purposes in many Asian countries. In the present study, the effect of OA on induction of autophagy in human hepatocellular carcinoma HepG2 and SMC7721 cells and the related mechanisms were investigated. MTT assay showed that OA significantly inhibited HepG2 and SMC7721 cells growth. OA treatment enhanced formation of autophagic vacuoles as revealed by monodansylcadaverine (MDC) staining. At the same time, increasing punctuate distribution of microtubule-associated protein 1 light chain 3 (LC3) and an increasing ratio of LC3-II to LC3-I were also triggered by OA incubation. In addition, OA-induced cell death was significantly inhibited by autophagy inhibitors 3-methyladenine (3-MA) and chloroquine (CQ) pretreatment. And we found out that OA can suppress the PI3K/Akt1/mTOR signaling pathway. Furthermore, our data suggested that OA-triggered autophagy was ROS-dependent as demonstrated by elevated cellular ROS levels by OA treatment. When ROS was cleared by N-acetylcysteine (NAC), OA-induced LC3-II convertsion and cell death were all reversed. Taken together, our results suggest that OA exerts anticancer effect via autophagic cell death in hepatocellular carcinoma.

• Journal of Microbiology and Biotechnology
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• v.30 no.10
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• pp.1543-1551
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• 2020

Panax ginseng has a wide range of activities including a neuroprotective effect, skin protective effects, enhanced DNA repairing, anti-diabetic activity, and protective effects against vascular inflammation. In the present study, we sought to discover the inhibitory effects of a mixture of natural products containing Panax ginseng, Ziziphus jujube, Rubi fructus, Artemisiae asiaticae and Scutellaria baicalensis (PZRAS) on osteoclastogenesis and bone remodeling, as neither the effects of a mixture containing Panax ginseng extract, nor its molecular mechanism on bone inflammation, have been clarified yet. PZRAS upregulated the levels of catalase (CAT), superoxide dismutase (SOD), glutathione reductase (GSH-R) and glutathione peroxidase (GSH-Px) and reduced malondialdehyde (MDA) in LPS-treated RAW264.7 cells. Moreover, treatment with PZRAS decreased the production of IL-1β and TNF-α. PZRAS also inhibited osteoclast differentiation through inhibiting osteoclastspecific genes like MMP-2, 9, cathepsin K, and TRAP in RANKL-treated RAW264.7 cells. Additionally, PZRAS has inhibitory functions on the RANKL-stimulated activation of ERK and JNK, which lead to a decrease in the expression of NFATc1 and c-Fos. In an in vivo study, bone resorption induced by LPS was recovered by treatment with PZRAS in bone volume per tissue volume (BV/TV) compared to control. Furthermore, the ratio of eroded bone surface of femurs was significantly increased in LPS-treated mice compared to vehicle group, but this ratio was significantly reversed in PZRAS-treated mice. These results suggest that PZRAS could prevent or treat disorders with abnormal bone loss.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.38 no.2
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• pp.189-195
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• 2012

Slim813 is a 2-cyclopentene-1-one oxime derivative with potent anti-inflammatory and anti-photoaging effects. Slim813 inhibited LPS-induced TNF-${\alpha}$ production and attenuated UVB-induced MMP1 expression. Here in an attempt to find an unrevealed efficacy of Slim813, we found that Slim813 stimulates lipolysis in a dose-dependent manner by increasing intracellular cAMP level through the elevation of HSL activity in fully differentiated adipocytes. Moreover, topical application of Slim813 for two weeks in human reduced the thickness of subcutaneous fat in arm and thigh regions, implying it could be effectively used in the reduction of unwanted local fat accumulation.

• Journal of Korean Medicine Rehabilitation
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• v.24 no.2
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• pp.31-40
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• 2014

Objectives Trachelospermi caulis, known as Nak-Suk-Deung in Korea, is the dried leafy stem of Trachelospermum asiaticum var. intermedium Nakai, and climbing stems and branches of Trachelospermum sdisyivum var, intermedium nakai or Apocyanaceae. Trachelospermi caulis has antipyretic and analgesic activity. It has traditionally been used as a folk remedy in Korea for the treatment of various infla mMatory diseases, including rheumatoid arthritis. The purpose of this study was to evaluate the Effects of Trachelospermum caulis extract on SNP-induced infla mMatory responses in rabbit HIG-82 synovial membrane cells. Methods Anti-infla mMatory effects of the extract of Trachelospermum caulis were investigated using rabbit HIG-82 synovial membrane cells. For this study, 3-(4,5-dimethylthiazol- 2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, western blot analysis, PGE2 i mMunoassay, and NO detection were conducted. Results The aqueous extract of Trachelospermum caulis exerted cytotoxicity and suppressed PGE2 synthesis and NO production in rabbit HIG-82 synovial membrane cells. The aqueous extract of Trachelospermum caulis also inhibited the SNP-induced expressions of COX-2, iNOS, and TNF-$\alpha$ in rabbit HIG-82 synovial membrane cells. Conclusions These results showed that the extract of Trachelospermum caulis exerts the anti-infla mMatory effect by suppressing COX-2, iNOS, and TNF-$\alpha$ expressions in the synovial membrane cells.