• Title/Summary/Keyword: TNF-β

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Protective Effects and Mechanisms of Salvia Miltiorrhizae Radix Extract on Endotoxin Shock (패혈증 쇼크에서 단삼 추출물의 억제 효과와 그 기전에 관한 연구)

  • Shin, Sang-Ho;Yun, Jeong-Min;Ko, Woo-Shin;Yoon, Hwa-Jung
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.29 no.3
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    • pp.14-26
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    • 2016
  • Objectives : This study was performed to investigate the protective effects and mechanisms of Salvia miltiorrhizae Radix extract (SME) on endotoxin shock.Methods : We used two models; LPS-induced sepsis model for in vivo model, and murine peritoneal macrophages responses for in vitro. SME was administrated orally to mice. After 1 hr, LPS was injected intraperitoneally. Survival rate was checked each time per 12 hr for 5 days. Mice were sacrificed 3 hr after LPS injection, then blood samples and organs were harvested. Cytokines secretion was measured by ELISA. Organs tissues were observed with microscope. Murine peritoneal macrophages were cultured for 1 hr either in a medium alone or in a medium that contained SME, as indicated. Then, the cells were treated with LPS for 24 hr. mRNA levels of cytokines were measured by real-time RT-PCR. Cytokine levels in the supernatants were measured by ELISA. The amount of nitrite was measured by using the Griess method to evaluate NO production. The cell lysates were analysed by Western blotting using antibodies for iNOS and β-actin was used as an internal control to monitor equal protein loading.Results : SME improverd the survival rate of mice model. SME inhibited the secretion of inflammatory cytokines and organs damages on Endotoxin Shock model. SME suppressed cytokine expression, cytokine secretion,NO production, iNOS expression in LPS-induced murine peritoneal macrophages.Conclusions : The results suggest that SME has protective effects on endotoxin shock through suppression of inflammatory cytokines, organ damages, NO production and so on.

Effects of Herbal Compounds with Tuna bone Powder on Rodent Osteoporosis Model Induced by Ovariectomy (Ca 혼합처방인 SG 및 GN이 난소절제 백서의 골다공증에 미치는 영향 연구)

  • Chi Gyoo Yong;Yoon Gun Ae;Kim Young Man
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.17 no.5
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    • pp.1281-1287
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    • 2003
  • In this research 2 sample compounds are made and analyzed in terms of the in vivo and in vitro effects on the ovariectomized rats. The 2 compounds are prescribed based on pathologic patterns of osteoporosis, and added calcium citrate from tuna bone powder. SG is for menopausal women(Type I osteoporosis) and GN is for senile men(Type II osteoporosis). Through these, SG manifested Significant effects on the T4, osteocalcin level, and through the histological changes of osteoid tissues and lipocytes. On the other hand GN showed significant increase on the biochemical markers of osteocalcin, TALP, even in histological features and bone mineral density and intensity of femur it showed meaningful changes. But In the results of RT-PCR on the IL-1β, IL-6, TNF α, there weren't coherent results with in vivo test, that is they were increased in the sample compound group than control group. These increase of bone resorption was seemed that those cytokines had the osteoclasts promote their own resorptive functions after fragments of bone tissues were increased in the cavity. And this clearance of inner fragments help the bone to strengthen its own substance. Putting together above facts, the sample compounds, SG and GN, made of tuna bone powder and herbal solutions are predicted that there would be pharmacological actions improving the osteoporosis initiated from the disorders of calcic absorption and increase of bone resorption. And GN has more effective actions than SG at least in the animal model.

MicroRNA-22 negatively regulates LPS-induced inflammatory responses by targeting HDAC6 in macrophages

  • Youn, Gi Soo;Park, Jong Kook;Lee, Chae Yeon;Jang, Jae Hee;Yun, Sang Ho;Kwon, Hyeok Yil;Choi, Soo Young;Park, Jinseu
    • BMB Reports
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    • v.53 no.4
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    • pp.223-228
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    • 2020
  • Dysregulation of histone deacetylase 6 (HDAC6) can lead to the pathologic states and result in the development of various diseases including cancers and inflammatory diseases. The objective of this study was to elucidate the regulatory role of microRNA-22 (miR-22) in HDAC6-mediated expression of pro-inflammatory cytokines in lipopolysaccharide (LPS)-stimulated macrophages. LPS stimulation induced HDAC6 expression, but suppressed miR-22 expression in macrophages, suggesting possible correlation between HDAC6 and miR-22. Luciferase reporter assays revealed that 3'UTR of HDAC6 was a bona fide target site of miR-22. Transfection of miR-22 mimic significantly inhibited LPS-induced HDAC6 expression, while miR-22 inhibitor further increased LPS-induced HDAC6 expression. LPS-induced activation of NF-κB and AP-1 was inhibited by miR-22 mimic, but further increased by miR-22 inhibitor. LPS-induced expression of pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6 was inhibited by miR-22 mimic, but further increased by miR-22 inhibitor. Taken together, these data provide evidence that miR-22 can downregulate LPS-induced expression of pro-inflammatory cytokines via suppression of NF-κB and AP-1 axis by targeting HDAC6 in macrophages.

Study on Antitumor Activity and Immunomodulatory effects of Seoleosojong-tang (활어소종탕이 항종역반응에 미치는 영향)

  • Son Ki Jeong;Park Yang Chun
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.18 no.1
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    • pp.137-147
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    • 2004
  • In order to evaluate the antitumor activity and immunomodulatory effects of Seoleosojong-tang(SST), studies were done. We measured the cytotoxic activity for various kinds of cancer cells, inhibitory effect on activity of DNA topoisomerase I, cell adhesion to complex extracellular matrix, survival time in ICR bearing S-180, pulmonary colonization and histological changes of lung in C57BL/6 injected i.v. with B16-F10, CAM assay, expression of CD4/sup +/, CD8/sup +/, B220/sup +/, cytokine gene in spleen cell. The results were obtained as follows: 1. In cytotoxicity against A549, HT1080, 816-F10, NCL-H661 was showed cytotoxicity as compared with control. 2. The inhibitory effect on adhesion of A549, 816-F10 to complex extracellular matrix was over 40% at 100 ㎍/㎖ of SST. 3. In DNA topoisomerase I assay, SST has inhibitory effect. 4. The T/C% was 120.8 in SST treated group in S-180 bearing ICR mice. 5. In pulmonary colonization assay, a number of colonies were decreased significantly and histological changes were showed that infiltration area of cancer cells were inhibited effectively in SST treated group. 6. In CAM Assay, SST has antiangiogenic effect. 7. On the expression of positive cell to CD4/sup +/, CD8/sup +/ and 8220/sup +/ in spleen cells, CD4/sup +/ cells were increased significantly in SST treated group. 8. Effect of SST on IL-1β gene expression in splenic cell was significantly increased as function of whole concentration. 9. The gene expression of IL-4, IL-6, IL-10, IL-12, IFN-γ, TNF-α were increased in SST treated group. From above results SST could be usefully applied for antitumor activity and immunomodulatory effects, but further research of SST should be required.

The anti-inflammatory effect of Portulaca oleracea 70% EtOH Extracts on lipopolysaccharide-induced inflammatory response in RAW 264.7 cells (LPS로 유도한 RAW 264.7 세포의 염증반응에서 마치현(馬齒莧) 70% 에탄올 추출물의 항염증 효과)

  • Seo, Sang-Wan
    • The Korea Journal of Herbology
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    • v.30 no.6
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    • pp.33-38
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    • 2015
  • Objectives : Portulaca oleracea (PO) have been used as a traditional medicine to treat inflammatory diseases in Korea. However, the anti-inflammatory effect of PO ethanol extract on lipopolysaccharide (LPS)-induced inflammation is not well-known. Therefore, this study was performed to identify the anti-inflammatory effect of PO on LPS induced inflammatory.Methods : Identification of PO was conducted by comparison with purified standards by HPLC. To measure out the cytotoxicity of PO, author performed the MTT assay. To evaluate the anti-inflammatory effects of PO, author examined the inflammatory mediators such as nitric oxide (NO) and pro-inflammatory cytokines (tumor necrosis factor (TNF)-α, interleukin, (IL)-1β and IL-6) on RAW 264.7 cells. Author also examined molecular mechanisms such as mitogen-activated protein kinases (MAPKs) and nuclear factor-B (NF-κB) activation by western blot.Results : Three major components (peaks 1, 2, 3) were detected in both varieties and peak 1 was characterized as caffeic acid, peak 2 as p-coumaric acid, and peak 3 as ferulic acid by comparison of chromatographic properties with authentic standards. Extract from PO itself did not have any cytotoxic effect in RAW 264.7 cells. PO inhibited LPS-induced productions of inflammatory mediators such as NO and pro-inflammatory cytokines in RAW 264.7cells. In addition, PO inhibited the phosphorylation of extracellular signal-regulated kinase1/2 (ERK1/2), c-Jun NH2-terminal kinase (JNK) and NF-κB activation in RAW 264.7 cells.Conclusions : Above experiment data can be an important indicator for the identification of PO and this study suggest that treatment of PO could reduce the LPS-induced inflammation. Thereby, PO could be used as a protective agent against inflammation.

Korean Red Ginseng exerts anti-inflammatory and autophagy-promoting activities in aged mice

  • Kim, Jin Kyeong;Shin, Kon Kuk;Kim, Haeyeop;Hong, Yo Han;Choi, Wooram;Kwak, Yi-Seong;Han, Chang-Kyun;Hyun, Sun Hee;Cho, Jae Youl
    • Journal of Ginseng Research
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    • v.45 no.6
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    • pp.717-725
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    • 2021
  • Background: Korean Red Ginseng (KRG) is a traditional herb that has several beneficial properties including anti-aging, anti-inflammatory, and autophagy regulatory effects. However, the mechanisms of these effects are not well understood. In this report, the underlying mechanisms of anti-inflammatory and autophagy-promoting effects were investigated in aged mice treated with KRG-water extract (WE) over a long period. Methods: The mechanisms of anti-inflammatory and autophagy-promoting activities of KRG-WE were evaluated in kidney, lung, liver, stomach, and colon of aged mice using semi-quantitative reverse transcription polymerase chain reaction (RT-PCR), quantitative RT-PCR (qRT-PCR), and western blot analysis. Results: KRG-WE significantly suppressed the mRNA expression levels of inflammation-related genes such as interleukin (IL)-1β, IL-8, tumor necrosis factor (TNF)- α, monocyte chemoattractant protein-1 (MCP-1), and IL-6 in kidney, lung, liver, stomach, and colon of the aged mice. Furthermore, KRG-WE downregulated the expression of transcription factors and their protein levels associated with inflammation in lung and kidney of aged mice. KRG-WE also increased the expression of autophagy-related genes and their protein levels in colon, liver, and stomach. Conclusion: The results suggest that KRG can suppress inflammatory responses and recover autophagy activity in aged mice.

Morin alleviates fructose-induced metabolic syndrome in rats via ameliorating oxidative stress, inflammatory and fibrotic markers

  • Heeba, Gehan Hussein;Rabie, Esraa Mohamed;Abuzeid, Mekky Mohamed;Bekhit, Amany Abdelrehim;Khalifa, Mohamed Montaser
    • The Korean Journal of Physiology and Pharmacology
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    • v.25 no.3
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    • pp.177-187
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    • 2021
  • Metabolic syndrome (MBS) is a widespread disease that has strongly related to unhealthy diet and low physical activity, which initiate more serious conditions such as obesity, cardiovascular diseases and type 2 diabetes mellitus. This study aimed to examine the therapeutic effects of morin, as one of the flavonoids constituents, which widely exists in many herbs and fruits, against some metabolic and hepatic manifestations observed in MBS rats and the feasible related mechanisms. MBS was induced in rats by high fructose diet feeding for 12 weeks. Morin (30 mg/kg) was administered orally to both normal and MBS rats for 4 weeks. Liver tissues were used for determination of liver index, hepatic expression of glucose transporter 2 (GLUT2) as well as both inflammatory and fibrotic markers. The fat/muscle ratio, metabolic parameters, systolic blood pressure, and oxidative stress markers were also determined. Our data confirmed that the administration of morin in fructose diet rats significantly reduced the elevated systolic blood pressure. The altered levels of metabolic parameters such as blood glucose, serum insulin, serum lipid profile, and oxidative stress markers were also reversed approximately to the normal values. In addition, morin treatment decreased liver index, serum liver enzyme activities, and fat/muscle ratio. Furthermore, morin relatively up-regulated GLUT2 expression, however, down-regulated NF-κB, TNF-α, and TGF-β expressions in the hepatic tissues. Here, we revealed that morin has an exquisite effect against metabolic disorders in the experimental model through, at least in part, antioxidant, anti-inflammatory, and anti-fibrotic mechanisms.

Aqueous extract of Jigal-san ameliorates acute inflammatory responses in RAW 264.7 cells and rats (NF-𝜅B 및 MAPK억제를 통한 지갈산(止渴散) 물추출물의 염증억제효과)

  • Jeong, Deok Ja;Park, Sang Mi;Kim, Sang Chan
    • Herbal Formula Science
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    • v.29 no.4
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    • pp.205-227
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    • 2021
  • Objectives : Jigal-san (JGS, 止渴散) has been used in East Asia including Korea, Japan and China for the treatment of breast inflammatory disorders and severe thirst. JGS originated from Euimunpalbeob (醫門八法; Yimenbafa) composed of Lonicerae Flos and Taraxaci Herba. According to previous studies Lonicerae Flos and Taraxaci Herba have an anti-inflammatory effect, respectively. But, there is no studies regarding on the effects of JGS in the immunological activities. The present study evaluated the anti-inflammatory effects of JGS in vitro and in vivo. Methods : Cell viability was evaluated by MTT assay, and NO was evaluated by content of the nitrite content in culture medium. TNF-α, IL-1β and IL-6 were quantified by ELISA. The protein expression of NF-κB, MAPKs, and iNOS were assessed by western blot analysis. Furthermore, the effects of JGS on acute inflammation were observed in rat paw edema model. Results : The JGS ameliorates the LPS-activated changes in the protein expression of NF-κB, p-JNK, and iNOS, as well as the production of NO and pro-inflammatory cytokines. In rat paw edema study, administration of 0.3 and 1.0 g/kg of JGS for 4 consecutive days inhibited the carrageenan (CA)-induced increases of edema and iNOS expression. Conclusions : These results demonstrate that JGS has anti-inflammatory effect in LPS-stimulated RAW 264.7 cells through decreasing the production of inflammatory mediators, via suppression of the NF-κB and MAPK pathways (JNK, not p-38 and ERK). In addition, the results of the CA-induced paw edema indicate that JGS ameliorates an inflammatory edema. Therefore, the present study could provide scientific evidence for the anti-inflammatory effect of JGS as well as the underlying mechanisms.

In vitro Immunostimulatory Activity of Bok Choy (Brassica campestris var. chinensis) Sprouts in RAW264.7 Macrophage Cells

  • Geum, Na Gyeong;Yeo, Joo Ho;Yu, Ju Hyeong;Choi, Min Yeong;Lee, Jae Won;Baek, Jueng Kyu;Jeong, Jin Boo
    • Korean Journal of Plant Resources
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    • v.34 no.3
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    • pp.203-215
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    • 2021
  • Bok choy is one of Brassica vegetables widely consumed worldwide. Brassica vegetables have been reported to exert various pharmacological activities such as antioxidant, anti-cancer and cardioprotective activity. However, studies on immunostimulatory activity of bok choy sprout have not been conducted properly. Thus, in this study, we investigated in vitro immunostimulatory activity of bok choy sprout extract (BCS) using mouse macrophage RAW264.7 cells. Our results showed that BCS increased the production of immunomodulators such as NO, iNOS, IL-1β, IL-6, IL-12, TNF-α and MCP-1, and phagocytic activity in RAW264.7 cells. BCS activated MAPK, NF-κB and PI3K/AKT signaling pathways. However, BCS-mediated production of immunomodulators was dependent on JNK, NF-κB and PI3K/AKT signaling pathways. the mRNA expression of TLR2 were significantly increased by BCS, TLR2 inhibition by anti-TLR2 dramatically suppressed the production of immunomodulators by BCS. In addition, TLR2 inhibition by anti-TLR2 significantly reduced BCS-mediated phosphorylation level of AKT, JNK and NF-κB. From these results, BCS may have immunostimulatory activity via TLR2-MAPK, NF-κB and PI3K/AKT signaling pathways. Therefore, BCS expected to be used as a potential immune-enhancing agent.

Anti-Inflammatory Effect of Hexane Fraction from Eisenia bicyclis on Lipopolysaccharides-Treated RAW 264.7 Cells (LPS로 유도된 RAW 264.7 대식세포에 대한 대황(Eisenia bicyclis) 헥산 분획물의 항염증 효과)

  • Kim, Bowoon;Choi, Chang-Geun;Kim, Jae-Il;Kim, Hyeung-Rak
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.54 no.2
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    • pp.152-161
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    • 2021
  • Eisenia bicyclis is known to have secondary metabolites exhibiting various biological activities. In a preliminary study, the n-hexane fraction obtained from the ethanolic extract of E. bicyclis showed higher anti-inflammatory activity than the ethyl acetate and butyl alcohol fractions based on the inhibition of lipopolysaccharide (LPS)-stimulated nitric oxide (NO) production in RAW 264.7 cells. Using this fraction (E. bicyclis hexane fraction, EHF), we investigated the molecular mechanisms underlying its anti-inflammatory effect in LPS-stimulated RAW 264.7 cells. Pretreatment of the cells with up to 50 ㎍/mL EHF significantly inhibited NO and prostaglandin E2 production as well as their responsible enzyme proteins and mRNAs, in a dose-dependent manner (P<0.05). Similarly, EHF markedly reduced the production of pro-inflammatory cytokines, such as interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α as well as their mRNA levels. Nuclear translocation of nuclear factor-kappa B (NF-κB) was strongly suppressed by EHF treatment. EHF significantly reduced the phosphorylation of mitogen-activated protein kinases and phosphatidylinositol 3-kinase/Akt in LPS-stimulated cells. Moreover, EHF reduced ear edema in phorbol myristate acetate (PMA)-induced mice. These results indicate that EHF contains potent anti-inflammatory compounds, which may be used as a dietary supplement for the prevention of inflammatory diseases.