• Title/Summary/Keyword: anti-tumor effect

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Bojungikgitang Inhibits LPS Plus $Interferon-{\gamma}-induced$ Inflammatory Mediators in RAW 264.7 Macrophages (보중익기탕(補中益氣湯)의 Lipopolysaccharide와 $Interferon-{\gamma}$에 의해 유도되는 염증성 매개물에 대한 억제 효과(效果))

  • Jang Seon-Il;Kim Hyung-Jin;Kim Young-Jun;Pae Hyun-Ock;Chung Hun-Taeg;Yun Yong-Gab;Jeong Ok-Sam;Kim Youn-Chul
    • Herbal Formula Science
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    • v.11 no.1
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    • pp.115-128
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    • 2003
  • Bojungikgitang is the water extracts prepared from Ginseng Radix, Astragali Radix, Angelicae gigantis Radix, Astractylodis Rhizoma alba, Aurantii nobilis Pericarpium, Glycyrrhizae Radix, Bupleuri Radix, Cimicifugae Rhizoma, which has been used for the treatment of indigestion, and immunological disease in oriental countries. In this study, the effects of Bojungikgitang on the productions of nitiric oxide (NO) and prostaglandin $E_2\;(PGE_2)$, and the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were examined using RAW 264.7 macrophages activated with $interferon-{\gamma}\;(IFN-{\gamma})$ plus lipopolysaccharide (LPS). Bojungikgitang (10-400 ${\mu}$g/ml) per se had no cytotoxic effect in unstimulated macrophages, but this compound dose-dependently reduced the release of NO and $PGE_2$ caused by stimulation of $LPS/IFN-{\gamma}$. The levels of iNOS and COX-2 protein were markedly suppressed by the treatment with Bojungikgitang in a concentration dependent manner. Moreover, Bojungikgitang also attenuated the production of tumor necrosis factor (TNF)-${\alpha}$, interleukin (1L)-1${\beta}$ and IL-6 in LPS-stimulated RAW 264.7 macrophages. These results suggest that Bojungikgitang decreases the NO and $PGE_2$ production in macrophages by inhibiting iNOS and COX-2 expression and these properties may contribute to the anti-inflammatory activity of Bojungikgitang.

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The Effect of Pyrrosiae Herba Herbal-acupuncture at KI10 on Lipopolysaccharide Induced Nephritis in Rats (음곡에 시술한 석위약침이 Lipopolysaccharide로 유도된 흰쥐의 신장염에 미치는 영향)

  • Jang, Seung Hoon;Kim, Jea Hong;Yim, Yun Kyoung
    • Journal of Acupuncture Research
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    • v.32 no.3
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    • pp.15-25
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    • 2015
  • Objectives : The purpose of this study is to investigate the effects of Pyrrosiae Herba herbal-acupuncture(PH-HA) at $KI_{10}$(Umgok) on nephritis induced by lipopolysaccharide(LPS) in rats. Methods : Rats were assigned to four groups: normal, LPS, saline and PH-HA. Rats in the saline and PH-HA groups were treated with saline injection and PH-HA respectively at $KI_{10}$, three times over the period of one week. All animals, except those in the normal group, were injected intra-peritoneally with LPS to induce nephritis. WBC, in blood, tumor necrosis factor alpha(TNF-${\alpha}$), cytokine-induced neutrophil chemoattractant 1(CINC-1), blood urea nitrogen(BUN), creatinine in serum, urinal volume, total protein creatinine in urine, and renal myeloperoxidase (MPO) were analyzed. Results : 1. PH-HA group showed significantly reduced levels of serum BUN, serum creatinine, TNF-${\alpha}$, and CINC-1 compared to the LPS group. Furthermore, a significant increase in urine output and more significant decreases in total protein in urine and MPO in renal tissue were observed in the PH-HA group when compared to the LPS group. 2. The PH-HA group showed significantly reduced levels of serum creatinine and renal MPO, and a more significant increase in urine output compared to the saline group. Conclusions : According to these results, it is postulated that PH-HA at $KI_{10}$ has anti-inflammatory and renal-protective effects on LPS-induced nephritis in rats, and both acupoint $KI_{10}$ and the herb Pyrrosiae Herba made contributions to these effects. Further studies on the interaction between acupoint $KI_{10}$ and the herb Pyrrosiae Herba may be needed.

Analgesic Effect of Blue Honeysuckle on the Rat Menopausal Pain, Primary Dysmenorrhea (Estradiol benzoate 및 oxytocin 투여로 유발된 랫트 생리통 모델에서 댕댕이나무 열매 농축동결건조 분말의 진통 및 생리장애 개선 효과)

  • Joo, Si-Chan;Lee, Sang-nam;Choi, Seong-Hun;Park, Ji-Ha
    • The Korea Journal of Herbology
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    • v.35 no.6
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    • pp.55-68
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    • 2020
  • Objectives : We observed the possibilities that blue honeysuckle has favorable analgesic or refinement effects on the Primary dysmenorrhea (PD) in rats. Methods : Estradiol benzoate and oxytocin were used to induce the PD rat model. And Blue honeysuckle concentration lyophilized powders (BH) 500, 250 and 125 mg/kg and 500 mg/kg of Lonicerae Flos aqueous extract lyophilized powders (LF) were orally administered, once a day for 10 days at 30 min after each estradiol benzoate treatment. Then the changes on the body weights and gains during experimental periods, abdominal writhing response for analgesic activities, uterine weights, uterus lipid peroxidation, antioxidant defense system - glutathione contents, superoxide dismutase and catalase activities, NF-κB and COX-2 mRNA expressions were monitored with uterus histopathology including immunohistochemistry for tumor necrosis factor (TNF)-α and inducible nitric oxide synthase (iNOS).. Results : Inflammatory and oxidative stress mediated PD signs were favorably and dose-dependently inhibited by 10 days continuous oral administration of three different dosages of BH - 500, 250 and 125 mg/kg as comparable to those of indomethacin(IND) 5 mg/kg treated rats in BH 500 mg/kg administered PD rats, and similar to those of LF 500 mg/kg in BH 125 mg/kg, at least in a condition of the present PD rat model. Conclusions : The results suggest that BH has favorable analgesic and refinement activities on the estradiol benzoate and oxytocin treatment-induced PD signs through anti-inflammatory and antioxidative potentials.

Compound K attenuates stromal cell-derived growth factor 1 (SDF-1)-induced migration of C6 glioma cells

  • Kim, Hyuck;Roh, Hyo Sun;Kim, Jai Eun;Park, Sun Dong;Park, Won Hwan;Moon, Jin-Young
    • Nutrition Research and Practice
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    • v.10 no.3
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    • pp.259-264
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    • 2016
  • BACKGROUND/OBJECTIVES: Stromal cell-derived growth factor 1 (SDF-1), also known as chemokine ligand 12, and chemokine receptor type 4 are involved in cancer cell migration. Compound K (CK), a metabolite of protopanaxadiol-type ginsenoside by gut microbiota, is reported to have therapeutic potential in cancer therapy. However, the inhibitory effect of CK on SDF-1 pathway-induced migration of glioma has not yet been established. MATERIALS/METHODS: Cytotoxicity of CK in C6 glioma cells was determined using an EZ-Cytox cell viability assay kit. Cell migration was tested using the wound healing and Boyden chamber assay. Phosphorylation levels of protein kinase C $(PKC){\alpha}$ and extracellular signal-regulated kinase (ERK) were measured by western blot assay, and matrix metallopeptidases (MMP) were measured by gelatin-zymography analysis. RESULTS: CK significantly reduced the phosphorylation of $PKC{\alpha}$ and ERK1/2, expression of MMP9 and MMP2, and inhibited the migration of C6 glioma cells under SDF-1-stimulated conditions. CONCLUSIONS: CK is a cell migration inhibitor that inhibits C6 glioma cell migration by regulating its downstream signaling molecules including $PKC{\alpha}$, ERK1/2, and MMPs.

Effects of Bovine α-Lactalbumin Added with Oleic Acid and Microbial Transglutaminase on Cancer Cell Apoptosis (올레산과 미생물 유래 트랜스글루타미나제를 첨가한 우유 알파-락트알부민의 암세포사멸 효과)

  • Jeong, Ji-Eun;Hong, Youn-Ho
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.41 no.3
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    • pp.310-319
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    • 2012
  • In order to investigate the biological effects of conformational changes in the folding state of bovine ${\alpha}$-lactalbumin (${\alpha}$-La), the protein was prepared and classified as apo form, microbial transglutaminase (MTGase) added form, or bovine ${\alpha}$-La made lethal to tumor cell (BAMLET) form. Apo ${\alpha}$-La form showed weaker cancer cell inhibitory activity (apoptosis) than native ${\alpha}$-La, which suggests that the metal ion-like $Ca^{2+}$ had a positive effect, whereas BAMLET form showed strong cancer cell apoptotic activity. The BAMLET form seemed to be a molten globule structure that increased hydrophobicity. MTGase added to apo ${\alpha}$-La polymer showed similar anti-cancer activity as native ${\alpha}$-La, and it was well hydrolyzed by digestive enzymes. NMR results showed that BAMLET interacted with oleic acid and produced a complex.

Effects of Bikiwhan on the Anti-tumor Immune Responses in the Mouse (비기환이 항종양(抗腫瘍) 면역반응(免疫反應)에 미치는 영향(影響))

  • Moon, Byung-Ha;Moon, Goo;Mun, Seok-Jae
    • THE JOURNAL OF KOREAN ORIENTAL ONCOLOGY
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    • v.1 no.1
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    • pp.167-190
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    • 1995
  • Bikiwhan is one of the oriental medicines that have been used for the treatment of tumors since ancient times. However, the mechanism of the drug action is not closely surved. This study was made to investigate the effects of Bikiwhan on the innate immunity were analysed by measuring the functions of phagocytes, and those of specific immunity were analysed by measuring T and B cells activities. The followings are the results obtained from this study : 1. Bikiwhan has direct cytotoxic effects against human lymphoma cell lines (K562) in a dose dependent manner. 2. An administration of Bikiwhan increased allogenic immune response in the mouse. 3. An administration of Bikiwhan increased the antibodies formation against SRBC. 4. An administration of Bikiwhan enhanced the apperance of rosette forming cells in the spleen. 5. An administration of Bikiwhan decreased the delayed-type hypersensitivity against dinitrofluorobenzene. 6. An administration of Bikiwhan has no effect on natural killer cells. 7. Bikiwhan increased the phagocyte activity of peritoneal macrophages in vitro and in in vivo as well. 8. Bikiwhan depressed the formation of reactive oxygen intermediated in vitro and in vivo as well. 9. Bikiwhan has the capacity to make peritoneal macrophages secrete nitric oxide. The above results demonstrate that Bikiwhan has enhancing effects of immune responses against tumors by decreasing tissue demages caused by immune responses.

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The effect of Gagamchunggan-tang on lipopolysaccharide-induced expression of $NF{\kappa}-B$ downstream genes in HepG2 cell (Lipopolysaccharide로 유발된 HepG2 세포의 염증반응에 대한 가감청간탕의 효과에 대한 연구)

  • Kim Sung-Hwan;Seo Sang-Ho;Hong Sang-Hoon
    • The Journal of Internal Korean Medicine
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    • v.24 no.1
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    • pp.113-122
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    • 2003
  • Objective : The aim of this study was to evaluate the efficacy of Gagamchunggan-tang on anti-inflammation reaction with lipopolysaccharide (LPS)-induced HepG2 cell. Method : We examined the effects of the Gagamchunggan-tang, a traditional drug for liver inflammation, on the process of lipopolysaccharide(LPS)-induced nuclear factor-${\kappa}Bp65(NF-{\kappa}Bp65)$ activation in HepG2 cell. SDS-PAGE, Western blotting, Immunofluorescence staining were studied. Results : Immunoblot analysis showed that the level of nucleic $NF-{\kappa}Bp65$ was rapidly up-regulated and cytosolic inhibitory $I-{\kappa}B{\alpha}$ was down-regulated by LPS challenge. While Gagamchunggan-tang inhibited an increase of $NF-{\kappa}Bp65$ and degradation of $I-{\kappa}B{\alpha}$ in HepG2 cell. Besides LPS-induced expression of a group of genes, such as tumor necrosis factor-${\alpha}(TNF-{\alpha})$, inducible nitric oxide synthase(iNOS) and cyclooxygenase-2 (COX-2), are repressed by Gagamchunggan-tang. It may be concluded that Gagamchunggan-tang attenuates the progress of LPS-induced inflammation by reduction of $NF-{\kappa}Bp65$ activation. Conclusion : The Gagamchunggan-tang would be useful as a therapeutic agent for endotoxin-induced liver disease.

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Induction of Cell Death by Betulinic Acid through Induction of Apoptosis and Inhibition of Autophagic Flux in Microglia BV-2 Cells

  • Seo, Jeongbin;Jung, Juneyoung;Jang, Dae Sik;Kim, Joungmok;Kim, Jeong Hee
    • Biomolecules & Therapeutics
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    • v.25 no.6
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    • pp.618-624
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    • 2017
  • Betulinic acid (BA), a natural pentacyclic triterpene found in many medicinal plants is known to have various biological activity including tumor suppression and anti-inflammatory effects. In this study, the cell-death induction effect of BA was investigated in BV-2 microglia cells. BA was cytotoxic to BV-2 cells with $IC_{50}$ of approximately $2.0{\mu}M$. Treatment of BA resulted in a dose-dependent chromosomal DNA degradation, suggesting that these cells underwent apoptosis. Flow cytometric analysis further confirmed that BA-treated BV-2 cells showed hypodiploid DNA content. BA treatment triggered apoptosis by decreasing Bcl-2 levels, activation of capase-3 protease and cleavage of PARP. In addition, BA treatment induced the accumulation of p62 and the increase in conversion of LC3-I to LC3-II, which are important autophagic flux monitoring markers. The increase in LC3-II indicates that BA treatment induced autophagosome formation, however, accumulation of p62 represents that the downstream autophagy pathway is blocked. It is demonstrated that BA induced cell death of BV-2 cells by inducing apoptosis and inhibiting autophagic flux. These data may provide important new information towards understanding the mechanisms by which BA induce cell death in microglia BV-2 cells.

Optimum Condition for Mass Culture of Hairy Roots from Artemisia sylvatica MAX (국내 자생 그늘쑥 (Artemisia sylvatica MAX) 모상근의 대량배양을 위한 최적조건)

  • Shin, Sun-Hee;Yang, Deok-Cho
    • Journal of Plant Biotechnology
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    • v.30 no.1
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    • pp.65-71
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    • 2003
  • This research aims the production of anti-tumor substances through in vitro culture of hairy roots transformed by Agrobacterium rhizogenes in Artemisia sylvatica MAX and the effect of culture conditions on optimum growth of hairy roots. We investigated the optimum medium, pH, carbon source, sucrose, light, Fe and polyamine conditions of various lines of hairy roots (NK3, NK4, YX. NK3-10) induced from Artemisia sylvatica to increase the optimum growth of hairy roots. MS medium was the best for optimum growth of hairy root clone, NK3-S10. The optimum culture period was 4 weeks for NK3-S10. The optimum sucrose concentration was 3.5%. The optimum concentration of FeSO$_4$, spermine and spermidine was 0.1 mM, 10 mM and 100 mM, respectively.

Inhibitory Effect of Artemisinic Acid Isolated from Artemisia Annua L on the MDC in HaCaT Keratinocytes (HaCaT 각질형성세포에서 개똥쑥(Artemisia annua L) 유래 성분인 Artemisinic acid의 Macrophage-derived Chemokine 억제 효과)

  • Kang, Gyeoung-Jin;Kang, Na-Jin;Han, Sang-Chul;Koo, Dong-Hwan;Kim, Young-Soo;Lee, Jin-Hyuck;Kim, Sang-Chul;Park, Deok-Hoon;Lee, Jong-Sung;Kang, Hee-Kyung;Yoo, Eun-Sook
    • Korean Journal of Pharmacognosy
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    • v.43 no.3
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    • pp.217-223
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    • 2012
  • In the present study, we investigated anti-inflammatory activity of artemisinic acid in HaCaT cells and RAW264.7 cells. Artemisinic acid showed inhibitory activity on macrophage-derived chemokines (MDC) expression, a factor related with atopic dermatitis (AD), in interferon (IFN)-${\gamma}$ and tumor necrosis factor (TNF)-${\alpha}$-stimulated HaCaT cells. In the study on action mechanism, pretreated artemisinic acid reduced the phosphorylation of STAT1 and p38 and the degradation of $I{\kappa}B$ by IFN-${\gamma}$ and TNF-${\alpha}$ stimulations. However, artemisinic acid didn't show the inhibitory activity on LPS-induced inflammatory mediators (NO, $PGE_2$, IL-6) in RAW264.7 cell. These results indicate that artemisinic acid inhibits IFN-${\gamma}$ and TNF-${\alpha}$-induced MDC expression through inhibition of signal factors, STAT1, NF-${\kappa}B$, and p38, in HaCaT keratinocytes.