• BMB Reports
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• v.42 no.12
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• pp.794-799
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• 2009

The inhibition of nitric oxide (NO) and cyclooxygenase-2 (COX-2) production is considered to be a promising approach to the treatment of various diseases, including inflammation and cancer. In this study, we examined the effects of the Agrocybe chaxingu $\beta$-glucan (polysaccharide) on lipopolysaccaride (LPS)-induced nitric oxide (NO) and cyclooxygenase-2 (COX-2) expression in murine macrophage Raw 264.7 cells as well as 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced ear edema in mice. The polysaccharide significantly inhibited (P < 0.01) LPS-induced iNOS and COX-2 expression levels in the cells. Furthermore, topical application of polysaccharide resulted in markedly inhibited (P < 0.01) TPA-induced ear edema in mice. These results suggest that this polysaccharide may be used for NO- and COX-2-related disorders such as inflammation and cancer.

• BMB Reports
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• v.44 no.12
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• pp.787-792
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• 2011

We investigated whether silk fibroin peptide derived from the silkworm, Bombyx mori, could inhibit inflammation and enhance the anti-inflammatory activity of Tat-superoxide dismutase (Tat-SOD), which was previously reported to effectively penetrate various cells and tissues and exert anti-oxidative activity in a mouse model of inflammation. Inflammation was induced by topical treatment of mouse ears with 12-O-tetradecanoylphorbol-13-acetate (TPA). Histological, Western blot, and reverse transcription-polymerase chain reaction data demonstrated that silk fibroin peptide or Tat-SOD alone could suppress elevated levels of cyclooxygenase-2, interleukin-6, interleukin-1beta, and tumor necrosis factor-alpha induced by TPA. Moreover, silk fibroin peptide significantly enhanced the anti-inflammatory activity of Tat-SOD, although it had no influence on in vitro and in vivo transduction of Tat-SOD. Silk fibroin peptide exhibited anti-inflammatory activity in a mice model of inflammation. Therefore, silk fibroin peptide alone or in combination with Tat-SOD might be used as a therapeutic agent for various inflammatory diseases.

• Journal of Periodontal and Implant Science
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• v.25 no.3
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• pp.635-647
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• 1995

Human polymorphonuclear leukocytes(PMN) constitute a first line of defense against all forms of injury and microbial challenge, which share a common cell lineage with macrophage. Microbial component LPS activates macrophages to produce IL-1, MIP-1${\alpha}$, -1${\beta}$, TNF-${\alpha}$ and IL-6, etc. Those cytokines have autocrine function to the macrophages, and paracrine function to other cell such as PMN and affect them to produce some biological functions. Having a responsive homogeneous cell line, HL-60, offers us the possibility of studying extensively on the function of PMN, which were not possible previously with peripheral PMN, due to the short-lived nature and difficulty of getting a purified PMN. In the present study, I performed MIP-1 receptor binding assay using HL-60 cell and human peripheral PMN. Also, in vitro antimicrobial assay was performed using differentiated or undifferentiated HL-60 cell. Differentiation was induced by treatment with 500 M of $N^6,O^2-dibutyryl$ adenosine 3'5' cyclic monophosphate(dbcAMP) (PMN-like cell), or 20ng/ml of 12-O-tetradecanoylphorbol-13-acetate(TPA) (macrophage/monocyte-like cell). Receptors for MIP-1${\alpha}$ were identified on dbcAMP-treated HL-60 as well as peripheral PMN. However, bound radioactive MIP-1${\alpha}$ on differentiated HL-60 was much higher than that of peripheral PMN, which suggest receptor number of differentiated HL-60 cell is higher than that of peripheral PMN. Although both of TPA and dbcAMP treatment significantly enhanced antimicrobial action of HL-60 cell, dbcAMP-treated cell(PMN-like HL-60) killed S.aureus more effectively in this experiment. TPA or dbcAMP treatment significantly enhanced antimicrobial action of undifferentiated HL-60 cell. MIP-1${\alpha}$ further increased enhancing effect of TPA or dbcAMP. IL-1${\alpha}$, however, increased only dbcAMP-induced enhancing effect of antimicrobial action of HL-60 cell. These results suggest that differentiated HL-60 cell could replace peripheral PMN in analysis of various biological functions of cytokines on PMN cell.

• Natural Product Sciences
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• v.13 no.1
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• pp.33-39
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• 2007

Eleven polyhydroxyursane triterpenoids (PHUTs) were tested to determine their cytoprotective, immunosuppressive and anti-inflammatory effects. To compare the bioactivities of $19{\alpha}$-hydroxyursane-type triterpenoids {23-hydroxytormentic acid (6), its methyl ester (7), tormentic acid (8), niga-ichigoside $F_1$ (9),euscaphic acid (10) and kaji-ichigoside $F_1$ (11)} of the Rosaceae crude drugs (Rubi Fructus and Rosa rugosae Radix) with PHUTs possessing no $19{\alpha}-hydroxyl$ of Centella asiatica (Umbelliferae), the four PHUTs, asiaticoside (1), madecassoside (2), asiatic acid (3), and madecassic acid (4) were isolated from C. asiatica and 23-hydroxyursolic acid (5) from Cussonia bancoensis. Cytoprotective effects were assessed by measuring cell viabilities against cisplatin-induced cytotoxocity in $LLC-PK_1$, cells (proximal tubule, pig kidney) to determine whether these agents have protective effects against nephrotoxicity caused by cisplatin. The inhibitory effect of 11 PHUTS on nitric oxide (NO) and prostaglandin $E_2\;(PGE_2)$ were evaluated by measuring nitrite accumulation in lipopolysaccharide (LPS)-induced macrophage RAW 264.7 cells, and their anti-inflammatory effects were tested in 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse ear edema model. Six MHUTs (compounds 1, 2, 4, 6, 10, and 11) exhibited higher cell viabilities during cisplatin-induced cytotoxicity testing even at a concentration of $200\;{\mu}g/ml$ than cisplatin only-treated group, suggesting that ese compounds have the potentcytoprotective efffcts. Compounds 1 and 3 of the C. asiatica and niga-ichigoside $F_1$ exhibited no inhibitory effect on NO and/or $PGE_2$ production whereas other PHUTs produced mild to significant NO and/or $PGE_2$ production.The four compounds (2, 5, 9, and 10) potently inhibited mouse ear edema induced by TPA whereas two compounds (1 and 3) had no activity in this test. These results suggest that many PHUTs are potentchemopreventives. Structure-activity relationship (SAR) was also discussed in each assay with regard to the significant role of OHs at the position of 2, 3, 6, 19, and 23 and to the glycoside linkage at the 28-carboxyl.

• Journal of Ginseng Research
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• v.44 no.4
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• pp.580-592
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• 2020

Background: Radix et Rhizoma Ginseng (thereafter called ginseng) has been used as a medicinal herb for thousands of years to maintain people's physical vitality and is also a non-organ-specific cancer preventive and therapeutic traditional medicine in several epidemiologic and preclinical studies. Owing to few toxic side effects and strong enhancement on body immunity, ginseng has admirable application potential and value in cancer chemoprevention. The study aims at investigating the chemopreventive effects of ginseng on cutaneous carcinoma and the underlying mechanisms. Methods: The mouse skin cancer model was induced by 7,12-dimethylbenz[a]anthracene/12-O-tetradecanoylphorbol-13-acetate. Ultraperformance liquid chromatography/mass spectrometry was used for identifying various ginsenosides, the main active ingredients of ginseng. Comprehensive approaches (including network pharmacology, bioinformatics, and experimental verification) were used to explore the potential targets of ginseng. Results: Ginseng treatment inhibited cutaneous carcinoma in terms of initiation and promotion. The content of Rb1, Rb2, Rc, and Rd ginsenosides was the highest in both mouse blood and skin tissues. Ginseng and its active components well maintained the redox homeostasis and modulated the immune response in the model. Specifically, ginseng treatment inhibited the initiation of skin cancer by enhancing T-cell-mediated immune response through upregulating HSP27 expression and inhibited the promotion of skin cancer by maintaining cellular redox homeostasis through promoting nuclear translocation of Nrf2. Conclusion: According to the study results, ginseng can be potentially used for cutaneous carcinoma as a chemopreventive agent by enhancing cell-mediated immunity and maintaining redox homeostasis with multiple components, targets, and links.

• Journal of the Korean Society of Food Science and Nutrition
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• v.41 no.4
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• pp.462-470
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• 2012

Mountain cultivated ginseng (MCG) is a type of Panax ginseng C. A. Mayer, grown in the mountains by artificial seeding. In general, it has been known that the biophysical activities of MCG is greater than that of ginseng. However, the in vivo efficacy of MCG on cancer has not been studied. In this study, we investigated the anti-carcinogenic effect of MCG and ginseng using the 7,12-dimethylbenz[a]anthracene (DMBA)-12-O-tetradecanoylphorbol- 13-acetate (TPA) two stage mouse skin carcinogenesis model. Six weeks of female ICR mice were divided into control, MCG, and ginseng diet groups and were subjected into two different experimental protocols. In the first study, each experimental diet was fed with TPA promotion for 24 weeks. The result showed that supplementation of MCG reduced tumor incidence, tumor multiplicity, and tumor size compared to those of the control and ginseng groups. In the second study, 3 groups of mice were supplied with each diet 4 weeks before DMBA tumor initiation, until the end of experiment. The result showed that tumor incidence, tumor multiplicity, and tumor size were reduced in the ginseng diet group compared to those of the control and MCG groups. TPA-induced BrdU incorporation was also significantly reduced in the ginseng diet group. Taken together, these results suggest that MCG is chemotherapeutic, whereas ginseng has a chemopreventative effect on mouse skin cancer.

• Journal of the Korean Society of Food Science and Nutrition
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• v.42 no.3
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• pp.384-388
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• 2013

This study investigated the anti-inflammatory effects of extracts from Caesalpinia sappan L. (CSL) on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced ear edema in mice. Skin inflammation was detected by immunohistochemistry and the protein and mRNA expression levels of cyclooxygenase-2 (COX-2) and cytokines (IL-6, IL-$1{\beta}$ and TNF-${\alpha}$) detected by Western blotting and RT-PCR. The activation of nuclear factor-kappa B (NF-${\kappa}B$) and mitogen-activated protein kinase (MAPK) were analyzed by Western blotting. CSL extracts markedly inhibited the TPA-induced expression of COX-2 and pro-inflammatory cytokines. Also, CSL extracts significantly reduced the activation of NF-${\kappa}B$ and MAPK. These results suggest that CSL extracts may serve as therapeutic agents against skin diseases related to inflammation.

• Journal of Physiology & Pathology in Korean Medicine
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• v.27 no.6
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• pp.782-788
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• 2013

Chrysanthemum zawadskii Herbich var. latilobum Kitamura (Compositae), colloquially known "Gujulcho" in Korea, has been used in traditional medicine for the treatment of various diseases, including cough, common cold, bladder-related disorders, gastroenteric disorders, hypertension, and inflammatory diseases, such as pneumonia, bronchitis, pharyngitis, and rheumatoid arthritis (RA) However, the effect of Chrysanthemum zawadskii var. latilobum on breast cancer invasion is unknown. In this study, we investigated the inhibitory effect of Chrysanthemum zawadskii var. latilobum extract (CZE) on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced matrix metalloproteinase-9 (MMP-9) expression and cell invasion, as well as the molecular mechanisms involved in MCF-7 cells. CZE were not cytotoxic up to 100 ${\mu}g/ml$ concentration in the MCF-7 cell line. CZE decreased MMP-9 expression. TPA substantially increased NF-${\kappa}B$ DNA binding activity. Pre-treatment with CZE inhibited TPA-stimulated NF-${\kappa}B$ binding activity and NF-${\kappa}B$ related protein expression. To identify invasion ability of MCF-7 cells decreased by CZE, we used martrigel invasion assay. As a result, it is significantly decreased cell invasion. These results indicate that CZE-mediated inhibition of TPA-induced MMP-9 expression and cell invasion involves the suppression of the NF-${\kappa}B$ pathway in MCF-7 cells. Chrysanthemum zawadskii var. latilobum may have potential value in restricting breast cancer metastasis.

• Journal of Life Science
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• v.27 no.3
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• pp.310-317
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• 2017

Mammalian cells control cellular homeostasis using a variety of defensive enzymes in order to combat against environmental oxidants and electrophiles. NF-E2-related factor-2 (NRF2) is a transcription factor that, in response to an exposure to oxidative stress, translocates into the nucleus and modulates the inducible expression of various phase II cytoprotective enzymes by binding to the antioxidant response element (ARE). In the present study, we have acquired 400 ethanol extracts of traditional medicinal plants and attempted to find out possible extract(s) that can increase the NRF2/ARE-dependent gene expression in human keratinocytes. As a result, we have identified that ethanol extracts of Rheum undulatum and Inula japonica strongly activated the ARE-dependent luciferase activity in HaCaT- ARE-luciferase cells. Exposure of ethanol extracts of Rheum undulatum and Inula japonica increased the viability and activated transcription and translation of NRF2-dependent phase II cytoprotective enzymes in HaCaT cells, such as heme oxygenase-1 (HO-1) and NAD[P]H:quinone oxidorecutase-1 (NQO1). In addition, ethanol extracts of Rheum undulatum and Inula japonica suppressed 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced generation of intracellular reactive oxygen species (ROS), thereby inhibiting the formation of 8-hydroxyguanosine (8-OHG) and 4-hydroxynonenal (4-HNE) in HaCaT cells. Together, our results demonstrate that ethanol extracts of Rheum undulatum and Inula japonica exert anti-oxidant effects via the induction of NRF2/ARE-dependent gene expression in human keratinocytes.

• BMB Reports
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• v.44 no.5
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• pp.329-334
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• 2011

Many proteins with poor transduction efficiency were reported to be delivered to cells by fusion with protein transduction domains (PTDs). In this study, we investigated the effect of levosulpiride on the transduction of PEP-1 ribosomal protein S3 (PEP-1-rpS3), and examined its influence on the stimulation of the therapeutic properties of PEP-1-rpS3. PEP-1-rpS3 transduction into HaCaT human keratinocytes and mouse skin was stimulated by levosulpiride in a manner that did not directly affect the cell viability. Following 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation in mice, levosulpiride alone was ineffective in reducing TPA-induced edema and in inhibiting the elevated productions of inflammatory mediators and cytokines, such as cyclooxygenase-2, inducible nitric oxide synthase, interleukin-6 and -1${\beta}$, and tumor necrosis factor-${\alpha}$. Anti-inflammatory activity by PEP-1-rpS3 + levosulpiride was significantly more potent than by PEP-1-rpS3 alone. These results suggest that levosulpiride may be useful for enhancing the therapeutic effect of PEP-1-rpS3 against various inflammatory diseases.