• Title/Summary/Keyword: tumor necrosis factor

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Comparative Study on Biological Activities and Ingredient Contents of Different Solvent Extracts of Samchulkunbi-tang (삼출건비탕의 추출용매에 따른 성분 함량 및 효능 비교 연구)

  • Jin, Seong Eun;Seo, Chang-Seob;Ha, Hyekyung;Lim, Hye-Sun;Kim, Yeji;Jeon, Woo-Young;Yoo, Sae-Rom;Kim, Jung-Hoon;Shin, In-Sik;Kim, Seong-Sil;Shin, Na Ra;Lee, Mee-Young;Jeong, Soo-Jin;Kim, Ohn Soon;Shin, Hyeun-Kyoo
    • Korean Journal of Pharmacognosy
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    • v.43 no.4
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    • pp.328-337
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    • 2012
  • In order to investigate anti-inflammatory, anti-allergic and anti-obesity activities of Samchulkunbi-tang (SCT; Shen zhu jian pi-tang) water and 70% ethanol (EtOH) extracts, in vitro inhibitory activities against nitric oxide (NO), prostaglandin $E_2$ $PGE_2$), interleukin (IL)-6 and tumor necrosis factor (TNF)-${\alpha}$ production in lipopolysaccharide-stimulated RAW 264.7 cells, and macrophage-derived chemokine (MDC/CCL22) and regulated on activation of normal T-cell-expressed and -secreted (RANTES/CCL5) production in TNF-${\alpha}$/interferon-${\gamma}$-stimulated HaCaT and BEAS-2B cells as well as glycerol-3-phosphate dehydrogenase (GPDH) activity and leptin production in 3T3-L1 cells were determined. A HPLC was used for quantification of the seven marker components (albiflorin, paeoniflorin, liquiritin, naringin, hesperidin, poncirin and glycyrrhizin) of SCT water and 70% EtOH extracts. SCT showed inhibitory effects against MDC and RANTES production in HaCaT cells, as well as RANTES production in BEAS-2B cells. In addition, SCT reduced not only NO, $PGE_2$, IL-6 and TNF-${\alpha}$ production in RAW 264.7 cells, but also GPDH activity and leptin production in 3T3-L1 cells. Furthermore, the biological activities and the contents of six compounds (except paeoniflorin) were higher in 70% EtOH extract than water extract. These results suggest that SCT has anti-inflammatory, anti-allergic and anti-obesity activities. These efficacies of 70% EtOH extract are relatively higher than that of water extract.

A Study on Pulmonary Toxic Effect of High-Dose Cisplatin Administered by Isolated Lung Perfusion in Dogs (잡견에서 분리폐관류 방법으로 투여된 고농도 cisplatin의 페독성에 관한 연구)

  • 김관민;한정호;김주현
    • Journal of Chest Surgery
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    • v.33 no.9
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    • pp.697-706
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    • 2000
  • Background: Isolated lung perfusion(ILP) was developed as a new treatment approach to non-resectable primary or metastatic lung cancer, because of its ability to reduce systemic toxicity while delivering high-dose chemotherapeutic agents to the target organs. This research was planned to evaluate the direct toxic effect of high-dose cisplatin to the lung tissue during isolated lung perfusion. Material and Method: Fifteen mongrel dogs were divided in the perfusate for 40 minutes. The second group was composed of 5 mongrel dogs which underwent ILP with cisplatin 2.5 mg/Kg added to the perfusate for 30 minutes and 10 minutes with washing solution without cisplatin. The third group underwent the same procedure as the second group except cisplatin 5.0 mg/Kg in the perfusate. Activities of serum angiotensin converting enzyme(ACE), tumor necrosis factor-$\alpha$(TNF-$\alpha$), and concentration of serum lactate dehydrogenase(LDH) and blood urea nitrogen/creatinine (BUN/Cr) were analyzed in each groups at the time of pre-perfusion, 1 hour, 1 day, 1 week, and 2 weeks after ILP. Result: Serum ACE activities before and 1 hour, 1 day, 1 week, and 2 weeks after ILP in control group were 45.1$\pm$6.3, 44.6$\pm$9.3, 46.7$\pm$9.5, 50.8$\pm$9.1, 46.1$\pm$4.3 U/L. Those in cisplatin 2.5 and 5.0 mg/Kg groups were 49.4$\pm$12.6, 39.0$\pm$8.6, 42.3$\pm$15.9, 50.0$\pm$2.6, 53.8$\pm$8.3 and 55.5$\pm$12.3, 47.0$\pm$6.3, 45.1$\pm$6.9, 74.8$\pm$19.5, 60.2$\pm$12.0 U/L, respectively. Serum TNF-$\alpha$ activities in each group before and after ILP were 5.0$\pm$1.5 / 7.7$\pm$2.2 / 6.6$\pm$2.5 / 4.3$\pm$1.3 / 5.2$\pm$1.1(control), 8.7$\pm$1.6 / 9.9$\pm$2.2 / 7.9$\pm$1.5 / 6.3$\pm$2.2 / 7.4$\pm$2.4 (cisplatin 2.5 mg/Kg), and 6.9$\pm$0.7 / 8.9$\pm$3.4 / 7.9$\pm$4.0 / 3.3$\pm$0.9 / 5.8$\pm$1.3 pg/ml(cisplatin 5.0 mg/Kg). Mean LDH levels of each group were 225.7 / 271.3 / 328.9 / 350.8 / 255.7(control), 235.7 / 265.7 / 336.0 / 379.5 / 299.2 (cisplatin 2.5 mg/Kg), and 259.6 / 285.2 / 340.6 / 433.4 / 292.4 IU/L(cisplatin 5.0 mg/Kg). So there was no significant difference in serum ACE, TNF-$\alpha$, and LDH activity changes after ILP between the 3 groups. And, there was no significant changes in BUN/Cr in each groups, which was independent of ILP and perfused concentration of cisplatin. In addition, all dogs survived the ILP and there was no significant evidence of pulmonary vascular injury after 2 weeks of ILP with cisplatin. Conclusion: There was no harmful effect of cisplatin to the lund tissue of the mongrel dog up to 5.0 mg/Kg in perfusate. Therefore, it is perceived to be safe and effective to deliver high-dose cisplatin to the lung without pulmonary toxicity and renal damage with ILP.

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Effects of Supercritical Fluid Marc Extracts from Actinidia polygama Max. on Inflammation and Atherosclerosis (개다래 초임계 박추출물이 염증 및 동맥경화에 미치는 영향)

  • Yu, Mi-Hee;Chae, In-Gyeong;Choi, Jun-Hyeok;Im, Hyo-Gwon;Choi, Hee-Don;Yang, Seun-Ah;Lee, Jin-Ho;Lee, In-Seon
    • Korean Journal of Food Science and Technology
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    • v.42 no.4
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    • pp.475-480
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    • 2010
  • The fruit of Actinidia polygama, Mock-chun-ryo in Korea, has been used as traditional medicine for abdominal pain, rheumatic arthritis, and stroke. In a previous study, the ethanol extract of A. polygama Max. showed antiinflammatory activity in RAW 264.7 cells. In this study, we investigated the anti-inflammatory and anti-atherosclerosis effects of supercritical fluid marc extracts from A. polygama Max. Anti-inflammatory extracts were produced from supercritical fluid extraction of the silver vine under the following conditions; pressure, 1,500-4,500 psi, temperature $35-55^{\circ}C$ and extraction time 1-2 hr. To evaluate the anti-inflammatory and anti-atherosclerotic effects of the extracts, we studied nitric oxide (NO), prostaglandin $E_2$ ($PGE_2$), and tumor necrosis factor-alpha (TNF-$\alpha$) levels in RAW 264.7 cells and MMP-9 activity in human aortic smooth muscle cells (HASMC). The Marc 11 extract inhibited the production of NO, $PGE_2$, and TNF-$\alpha$ by lipopolysaccharide in RAW 264.7 cells. Moreover, the marc 11 extract inhibited TNF-$\alpha$-induced MMP-9 activity in HASMC. These results indicate that the Marc 11 extract of A. polygama Max. has the potential for use as an anti-atherosclerosis agent.

Anti-inflammatory Effect of Oxya chinensis sinuosa Ethanol Extract in LPS-induced RAW 264.7 Cells (LPS로 유도된 RAW 264.7세포에 대한 벼메뚜기(Oxya chinensis sinuosa) 에탄올 추출물의 항염증 효과)

  • Yoon, Young-Il;Chung, Mi Yeon;Hwang, Jae-Sam;Goo, Tae-Won;Ahn, Mi-Young;Lee, Young-Bo;Han, Myung-Sea;Yun, Eun-Young
    • Journal of Life Science
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    • v.24 no.4
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    • pp.370-376
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    • 2014
  • Although the grasshopper Oxya chinensis sinuosa has long been used as food in Korea, there is little data on its functional effects. In this study, we investigated the anti-inflammatory effect of O. c. sinuosa ethanol extract (OCE) in RAW 264.7 mouse macrophage cells treated with lipopolysaccharide (LPS) for induction of inflammation. First, we determined that there is no cytotoxicity at $2,000{\mu}g/ml$ or less of OCE in RAW 264.7 cells. To evaluate the anti-inflammatory effects of OCE, we investigated expression levels of pro-inflammatory cytokines such as tumor necrosis factor (TNF)-${\alpha}$ and interleukin (IL)-6, and pro-inflammatory enzymes such as inducible nitric oxide synthase (iNOS) and cyclo-oxygenase-2 (COX-2) in LPS-induced RAW 264.7 cells. In addition, we examined whether OCE could inhibit translocation of NF-${\kappa}B$ p65 into the nucleus in LPS induced RAW 264.7 cells. As a result, we found that the mRNA and protein levels of TNF-${\alpha}$ and IL-6 decreased in LPS-induced RAW 264.7 cells after treatment with OCE in a dose-dependent manner. In addition, we confirmed a $2,000{\mu}g/ml$ concentration of OCE inhibited translocation of NF-${\kappa}B$ p65 by immunnostaining and Western blot analysis, and a decrease in the protein expression levels of iNOS and COX-2. Accordingly, we suppose that OCE has an anti-inflammatory effect through down-regulation of TNF-${\alpha}$, IL-6, iNOS, and COX-2 related to ${\kappa}B$ p65 inflammatory signaling pathways.

Inhibitory effect of Hypericum ascyron on pro-inflammatory responses in lipopolysaccharide-induced Raw 264.7 Cells (Lipopolysaccharide로 유도된 Raw 264.7 cell에서 물레나물(Hypericum asctron)의 Pro-inflammatory 억제 효과)

  • Hong, Eun-Jin;Park, Hye-Jin;Kim, Na-Hyun;Jo, Jae-Bum;Lee, Jae-Eun;Lim, Su-Bin;Ahn, Dong-Hyun;Jung, Hee-Young;Cho, Young-Je
    • Journal of Applied Biological Chemistry
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    • v.60 no.4
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    • pp.363-372
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    • 2017
  • Hypericum ascyron has long been used as medicinal plant and recent studies reported that H. ascyron has anti-diabetic, anti-oxidant, and anti-bacterial effects. In this study, inhibitory effect from H. ascyron on pro-inflammatory responses has been investigated. H. ascyron was extracted at optimal extraction condition. Total phenolic contents in water and 90% ethanol were 29.75 and 31.82 mg/g, respectively. Hyaluronidase inhibitory activity of H. ascyron extracts ($50-200{\mu}g/mL$ phenolics) was 0.00-14.81% and 15.33-47.49%, respectively. In cell viability, cell toxicity was shown at concentration of $100{\mu}g/mL$ and $30{\mu}g/mL$ of water and 90% ethanol extract. Therefore, $10-50{\mu}g/mL$ in water extracts and $5-20{\mu}g/mL$ in ethanol extracts was selected each for further study. Inducible nitric oxide synthase (iNOS) derived nitric oxide (NO) and cyclooxygenase (COX)-2-derived prostaglandin $E_2$ ($PGE_2$) protein expression inhibitory effect of extracts were inhibited in a dose dependent manner, significantly. Also, the pro-inflammatory cytokines inhibitory effect such as tumor necrosis $factor-{\alpha}$, nterleukin (IL)-6 and $IL-1{\beta}$ were decreased in the dose dependent manner. The results indicate that H. ascyron extracts reduced inflammatory responses in lipopolysaccharide-induced 264.7 cells via the regulation of the iNOS, COX-2, NO, $PGE_2$, and pro-inflammatory cytokines. Therefore, H. ascyron extracts have significant anti-inflammatory effect and a source as therapeutic materials.

Anti-inflammatory Activity of an Ethanol Extract of Laminaria japonica Root on Lipopolysaccharide-induced Inflammatory Responses in RAW 264.7 Cells (Lipopolysaccharide로 유도된 RAW 264.7 세포에서 다시마 뿌리 에탄올 추출물의 항염증 효과)

  • Kang, Bo-Kyeong;Kim, Koth-Bong-Woo-Ri;Kim, Min-Ji;Bark, Si-Woo;Pak, Won-Min;Kim, Bo-Ram;Ahn, Na-Kyung;Choi, Yeon-Uk;Ahn, Dong-Hyun
    • Korean Journal of Food Science and Technology
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    • v.46 no.6
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    • pp.729-733
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    • 2014
  • Laminaria japonica roots have not been used practically in Korea. In this study, in order to promote the use of these by-products, the anti-inflammatory activity of an ethanol extract of Laminaria japonica root (LJREE) was investigated using a lipopolysaccharide (LPS) to induce an inflammatory response in RAW 264.7 cells. To examine the potential anti-inflammatory effects of LJREE, levels of nitric oxide (NO) and pro-inflammatory cytokines, such as interleukin-6 (IL-6), tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), and interleukin-$1{\beta}$ (IL-$1{\beta}$), and cell proliferation were measured. We found that NO levels decreased in a dose-dependent manner, the production of IL-6, TNF-${\alpha}$, and IL-$1{\beta}$ was suppressed, and the production of IL-$1{\beta}$ was inhibited over 30% after treatment with $100{\mu}g/mL$ LJREE. In conclusion, the proliferation of RAW 264.7 cells, measured by MTT assay, confirmed that LJREE may have significant effects on inflammatory factors without any cytotoxicity, making it a potential anti-inflammatory agent.

Dietary Brown Seaweed Modulates Nutrient Metabolism, Anti-oxidant System and Immune Response in Broiler Chicks Injected LPS i.p. (사료 중 미역은 복강내 LPS 주입 육계 병아리에서 영양소 대사, 항산화계 및 면역 반응을 조정한다)

  • Park, In-Kyung;Im, Jin-Taek;Choi, Do-Yul;Koh, Tae-Song
    • Journal of Animal Science and Technology
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    • v.50 no.2
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    • pp.185-198
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    • 2008
  • Influences of dietary brown seaweed(BSW) on the nutrient metabolism, anti-oxidant enzyme activity and cell-mediated immune response were studied in broiler chicks activated acute phase response. 72 Hatched male broiler chicks(Ross) were divided into 12 pens, 6 heads per pen, and fed the BSW 0.0% (Basal) or 2.0% diet, respectively, and injected with the Salmonella typhimurium lipopoly saccharide(LPS) for activation of the acute phase response three times at 8, 10 and 12 d of age. During 4 wks of experimental feeding, growth performance of broiler chicks was not affected by dietary BSW and the acute phase response. Compared with control birds, the acute phase response did not affect the daily weight gain in birds fed BSW 2.0% diet, decreased nitrogen balance(NB) or metabolizable energy(ME) utilization per metabolic body size(kg0.75), and enhanced activities of peroxidase or extracellular SOD(EcSOD), tumor necrosis factor-alpha and ovotransferrin in plasma and MnSOD and CuZnSOD in erythrocyte cytosol. Compared to BSW 0.0% diet, 2.0% diet enhanced protein retention(NB) per kg0.75 regardless the acute phase response, did not affect uric acid nitrogen excretion(UAN) per kg0.75 in birds during the acute phase response, decreased(p<0.05) the UAN excretion per kg0.75 in control birds. And BSW 2.0% diet also decreased(p<0.05) plasma peroxide level and erythrocyte peroxidase or MnSOD activity but increased plasma peroxidase and EcSOD activity and interleukin-1 activity secreted from LPS-stimulated PBMC in 4 week broiler chicks.

Effect of Black Garlic Extract on Cytokine Generation of Mouse Spleen Cells (흑마늘(Black garlic) 추출물이 마우스 비장세포의 Cytokine 생성에 미치는 영향)

  • Seo, Min Jeong;Kang, Byoung Won;Park, Jeong Uck;Kim, Min Jeong;Lee, Hye Hyeon;Ryu, En Ju;Joo, Woo Hong;Kim, Kwang Hyuk;Jeong, Yong Kee
    • Journal of Life Science
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    • v.23 no.1
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    • pp.63-68
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    • 2013
  • The effect of black garlic extract on the activation of spleen cells from a C57BL6 mouse was investigated to examine immune activities of of fermented black garlic containing a variety of bioactive substances. xtract obtained from the concentration of commercial Namhae black garlic was used for the analysis of immune activities. Treatment with the extract increased the expression of interleukin-2 (IL-2) cytokine. The simultaneous administration of the extract plus lipopolysaccharide (LPS) increased the expression of IL-2, tumor necrosis factor (TNF)-${\alpha}$, and interferon (IFN)-${\gamma}$ compared with that of a control group. This result suggests that cellular immunity can be induced by macrophages, resulting in the expression of T lymphocytes and T helper type 1 (Th1) cells. In addition, treatment with the extract increased the late response of IL-6 cytokines, and the extract plus LPS augmented the expression of IL-4 and IL-6 compared with that of an LPS-treated group. Meanwhile, the extract plus LPS decreased the late response of IL-10, suggesting that humoral immunity can be activated by stimulating B lymphocytes, suppressing cellular immunity, and effectively modulating the conversion into humoral immune responses. These findings demonstrate that the black garlic extract activates Th1 and Th2 cells by stimulating T lymphocytes in mouse spleen cells and leads to immunomodulation by activating cellular and humoral immune responses of the immune system.

Lymphotoxin β Receptor Stimulation Is Linked to MLCK Activity and Suppresses Stress Fiber Formation in Agonistic Anti-LTβR Antibody-stimulated Fibroblastic Reticular Cells (FRC에서 agonistic anti-LTβR antibody의 LTβR 자극은 MLCK 연관성 및 stress fiber 형성에 대한 강력한 억제 작용)

  • Kim, Min Hwan;Lee, Jong-Hwan
    • Journal of Life Science
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    • v.27 no.10
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    • pp.1199-1206
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    • 2017
  • The lymphotoxin ${\beta}$ receptor ($LT{\beta}R$), a member of the tumor necrosis factor receptor family, plays an important role in lymphoid tissue's architecture and organogenesis. We found that $LT{\beta}R$ stimulation induced changes in stress fibers (SFs) in fibroblastic reticular cells (FRCs). MLCK and ROCK play critical roles in the regulation of SF formation in cells. The present study was performed to investigate the antifibrotic effects on SF regulation of $LT{\beta}R$ signaling, with a focus on MLCK inhibition. The effect of $LT{\beta}R$ on the SF change was analyzed using immunoblot and fluorescence assays and agonistic $anti-LT{\beta}R$ antibody-treated FRCs. In addition, we checked the level of Rho-guanosine diphosphate (GDP)/guanosine triphosphate (GTP) exchange activity with FRC lysate. Phospho-ezrin proteins acting as membrane-cytoskeleton linkers completely de-phosphorylated in agonistic $anti-LT{\beta}R$ antibody-treated FRCs. The actin bundles rearranged into SFs, where phospho-myosin light chain (p-MLC) co-localized in FRCs. ML7-treated FRCs completely blocked SFs and showed retraction and shrinkage processes comparable to those observed in agonistic $anti-LT{\beta}R$ antibody-treated cells. Inhibition of ROCK activity induced changes in the actin cytoskeleton organization; however, some SFs remained in the cells, while they were completely disrupted by MLCK inhibition with ML7. We showed that the phosphorylation of MLC was completely abolished with $LT{\beta}R$ stimulation in FRCs. When $LT{\beta}R$ was stimulated with the agonistic $anti-LT{\beta}R$ antibody, the Rho-GDP/GTP exchange activity was reduced, however, the activity was not completely abolished. Collectively, the results illustrated that MLCK was potently responsible for the SF regulation triggered via $LT{\beta}R$ signaling in FRCs.

Euphorbiae Immifusae Sensitizes Apoptosis of TRAIL-resistant Human Gastric Adenocarcinoma AGS Cells (지금초 추출물에 의한 TRAIL 저항성 인체위암세포의 세포사멸 유도)

  • Lee, Jae-Jun; Shin, Dong-Hyuk;Park, Sang-Eun;Kim, Won-Il;Park, Dong-Il;Choi, Yung-Hyun;Hong, Sang-Hoon
    • Journal of Life Science
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    • v.18 no.1
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    • pp.120-128
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    • 2008
  • The death ligand tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)/ Apo1L is a cytokine that activates apoptosis through cell surface death receptors. TRAIL has sparked growing interest in oncology due to its reported ability to selectively trigger cancer cell death. Euphorbiae humifusae Wind has been used in traditional Oriental medicine as a folk remedy used for the treatment of cancer. However, the mechanism responsible for the anticancer effects of E. humifusae not clearly understood. Here, we show that treatment with subtoxic doses of water extract of E. humifusae (WEEH) in combination with TRAIL induces apoptosis in TRAIL-resistant human gastric carcinoma AGS cells. Combined treatment with WEEH and TRAIL induced chromatin condensation and sub-G1 phase DNA content. These indicators of apoptosis were correlated with the induction of caspase activity that resulted in the cleavage of poly (ADP-ribose) polymerase. Combined treatment also triggered the loss of mitochondrial membrane potential. Furthermore, co-treatment with WEEH and TRAIL down-regulated the protein levels of the anti-apoptotic proteins such as Bcl-2, Bcl-xL, XIAP and cIAP-1. Although more study will be needed to examine the detailed mechanisms, this combined treatment may offer an attractive strategy for safely treating gastric adenocarcinomas and the results provide important new insights into the possible molecular mechanisms of the anticancer activity of E. humifusae.