• Journal of Korean Medicine Rehabilitation
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• v.28 no.2
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• pp.37-45
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• 2018

Objectives This study was designed to investigate whether the Gagamtongsoon-San (GT) has an inhibitory effect and its mechanisms are associated with the iNOS and COX-2. Methods Cytotoxic activity of GT extract on RAW264.7 cells was evaluated by using 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide (MTT) solution. Inflammatory condition was induced by LPS. NO production was measured using Griess reagent system. The expressions of iNOS and COX-2 mRNA and protein were determined by realtime PCR. The concentrations of PGE2 were measured by an enzyme immunoassay (EIA). Results The GT does not impair the cell viability in tested concentration $500{\mu}g/ml$ or below. GT significantly reduced the NO production in a dose-dependent manner. GT $500{\mu}g/ml$ also suppressed LPS-induced mRNA expressions of iNOS and COX-2. GT $500{\mu}g/ml$ reduced the PGE2 secretion in LPS induced RAW264.7 cells. Conclusions These outcomes show that GT extract has an anti-inflammatory activities. And also this conclusion can be the data that supports the GT's anti-inflammatory effect objectively.

• Biomolecules & Therapeutics
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• v.32 no.3
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• pp.309-318
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• 2024

Compared to other organs, the brain has limited antioxidant defenses. In particular, the hippocampus is the central region for learning and memory and is highly susceptible to oxidative stress. Glial cells are the most abundant cells in the brain, and sustained glial cell activation is critical to the neuroinflammation that aggravates neuropathology and neurotoxicity. Therefore, regulating glial cell activation is a promising neurotherapeutic treatment. Quinic acid (QA) and its derivatives possess anti-oxidant and anti-inflammatory properties. Although previous studies have evidenced QA's benefit on the brain, in vivo and in vitro analyses of its anti-oxidant and anti-inflammatory properties in glial cells have yet to be established. This study investigated QA's rescue effect in lipopolysaccharide (LPS)-induced behavior impairment. Orally administering QA restored social impairment and LPS-induced spatial and fear memory. In addition, QA inhibited proinflammatory mediator, oxidative stress marker, and mitogen-activated protein kinase (MAPK) activation in the LPS-injected hippocampus. QA inhibited nitrite release and extracellular signal-regulated kinase (ERK) phosphorylation in LPS-stimulated astrocytes. Collectively, QA restored impaired neuroinflammation-induced behavior by regulating proinflammatory mediator and ERK activation in astrocytes, demonstrating its potential as a therapeutic agent for neuroinflammation-induced brain disease treatments.

• Journal of Evidence-Based Herbal Medicine
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• v.1 no.1
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• pp.7-11
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• 2008

The purpose of this study was to investigate the anti-inflammatory effects of extract from Hwang lyun tang (HLT) on the THP-1 cell and HMC-1 cell. To evaluate of anti-inflammatory of HLT, we examined cytokines production in lipopolysacchride (LPS)-induced THP-1 cell and A23187, PMA-induced HMC-1 cell. Extract of HLT inhibit LPS-induced interleukin (IL)-8 production in human monocyte THP-1 cells. Extract of HLT inhibit A23187, PMA-induced IL-8, tumor necrosis factor-$\alpha$ (INF-$\alpha$) production in HMC-1 cells. HLT down-regulated LPS-induced IL-8 production and A23187, PMA-induced IL-8, TNF-$\alpha$ production, which may be provide a clinical basis for anti-inflammatory properities of HLT.

• Journal of Evidence-Based Herbal Medicine
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• v.1 no.1
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• pp.1-5
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• 2008

Objectives : The purpose of this study was to investigate the anti-inflammatory effects of extract from Jak-Yak Tang (JYT) on the THP-1 cell and HMC-1 cell. Method : To evaluate of anti-inflammatory of JYT, we examined cytokines production in lipopolysacchride (LPS)-induced THP-1 cell and A23187, PMA-induced HMC-1 cell. Result : Extract of JYT inhibit LPS-induced interleukin (IL)-8 production in human monocyte THP-1 cells. Extract of JYT inhibit A23187, PMA-induced IL-8, tumor necrosis factor-$\alpha$ (INF-$\alpha$) production in HMC-1 cells. Conclusion : NT down-regulated LPS-induced IL-8 production and A23187, PMA-induced IL-8, TNF-$\alpha$ production, which may be provide a clinical basis for anti-inflammatory properities of JYT.

• Korean Journal of Acupuncture
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• v.26 no.3
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• pp.43-54
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• 2009

Objectives : To investigate the anti-inflammatory effects of Prunella vulgaris pharmacopuncture in lipopolysaccharide (LPS)-induced inflammatory rat model. Methods : Sprague-Dawley rats were divided into 5 groups; normal control (n=8), LPS control (n=8), LPS+Prunella vulgaris pharmacopuncture at CV4 (CV4, n=8), LPS+Prunella vulgaris pharmacopuncture at ST36 (ST36, n=8), and LPS+Prunella vulgaris pharmacopuncture at CV12 (CV12, n=8). Pharmacopuncture was given every two days for 4 weeks followed by inflammation induction by peritoneal LPS injection (5mg/kg). Proinflammatory cytokines including interleukin-$1{\beta}$ (IL-$1{\beta}$), interleukin-6 (IL-6), tumor necrosis factor-$\alpha$ (TNF-$\alpha$), interleukin-10 (IL-10), thiobarbituric acid reactive substance (TBARS) from blood and liver tissue were compared before and 5 hrs after inflammation induction. Results : In CV4 and CV12 groups, plasma IL-$1{\beta}$, IL-6 and TNF-$\alpha$ levels increased by LPS injection, significantly decreased 5 hrs after injection (p<0.05). For CV12 group, plasma IL-10 concentration significantly increased (p<0.05). Liver IL-$1{\beta}$ and IL-6 levles significantly decreased in CV4 and CV12 groups (P<0.05), while normal and LPS control groups were not significantly different in TNF-$\alpha$ and IL-10 levels. Plasma TBARS concentration was significantly decreased in CV12 group, while there was no significant difference among LPS control and pharmacopuncture groups for liver TBARS concentration. Conclusions : Based on the present findings, Prunella vulgaris pharmacopuncture at CV12 may have a potentially preventive anti-inflammatory effect in an LPS-induced inflammatory rat model.

• Journal of Acupuncture Research
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• v.30 no.3
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• pp.61-73
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• 2013

Objectives : This study was designed to evaluate the effects of Phaseoli Semen Herbal-acupuncture(PS-HA) at $KI_{10}$ in acute nephritis induced by lipopolysaccharide(LPS) in rat. Methods : The rats were divided into 5 groups, which were control, LPS, PS-HA, NP and saline group. LPS, PS-HA, NP and saline groups were given LPS to induce acute nephritis and control group did not receive LPS. LPS group did not receive any treatment after the onset of acute nephritis. PS-HA, NP and saline group received PS-HA, normal acupuncture, and saline injection at $KI_{10}$ three times per week, respectively. To evaluate the effect of PS-HA at $KI_{10}$, the complete blood count, BUN, creatinine, TNF-${\alpha}$, and CINC-1 in serum were measured. To show its effect on renal function, creatinine, and total protein in urine was measured as well as urine output. The level of myeloperoxidase in renal tissue was quantified and complete histology was done in kidney samples obtained from the rats. Results : PS-HA group showed a significant reduction in the proportion of WBC and neutrophil, serum BUN, TNF-${\alpha}$, and CINC-1 compared to LPS group. Furthermore, a significant increase in urine output and a decrease in urinary creatinine level, MPO in renal tissue, and number of neutrophils at glomerulus was observed in PS-HA group compared to LPS group Conclusions : PS-HA at $KI_{10}$ was shown to have a significantly effect on treating LPS induced acute nephrits. Therefore, future study is needed to further evaluate the clinical usefulness of PS-HA at $KI_{10}$ in treating acute nephritis.

• Journal of Acupuncture Research
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• v.29 no.1
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• pp.15-24
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• 2012

Objectives : In recent years, many studies have been widely researching anti-inflammation effect of various medicinal plants. $Cinnamomi$ $Cortex$ was not enough in researching of the anti-inflammation. Moreover, there is no comparative study about extraction methods. Therefore, we investigated the inhibitory effects of $Cinnamomi$ $Cortex$ pharmacopuncture by EtOH and Hot water extraction on Nitric oxide(NO), Prostaglandin E2(PGE2) production, Cyclooxygenase(COX)-2, inducible NOS(iNOS) expression and extracellular signal regulate kinase(ERK)1/2 phosphorylation in lipopolysaccharide(LPS) induced RAW 264.7 macrophage cell. Methods : $Cinnamomi$ $Cortex$ was extracted by EtOH and Hot water. RAW 264.7 macrophage cell viability was measured by MTT assay. Effect of $Cinnamomi$ $Cortex$ pharmacopuncture on NO and PGE2 production in LPS induced macrophages was accessed by Griess assay and enzyme-linked immunospecific assay(ELISA), respectively. Inhibition effect on COX-2, iNOS expression and ERK1/2 phosphorylation was examined by Immunoblotting assay. Results : 1. Cytotoxic effect of $Cinnamomi$ $Cortex$ pharmacopuncture by Hot water extraction in RAW 264.7 macrophages was not appeared, except $3125{\mu}g/m{\ell}$. And cytotoxic effect was not appeared in EtOH extraction method. 2. $Cinnamomi$ $Cortex$ pharmacopuncture by EtOH and Hot water extraction inhibited NO production in LPS induced macrophages significantly. 3. $Cinnamomi$ $Cortex$ pharmacopuncture by EtOH and Hot water extraction inhibited PGE2 production in LPS induced macrophages significantly. 4. $Cinnamomi$ $Cortex$ pharmacopuncture by EtOH and Hot water extraction inhibited COX-2, iNOS expression in LPS induced macrophages. Especially, it has been confirmed that COX-2, iNOS expression were effectively inhibited in Hot water extraction. 5. $Cinnamomi$ $Cortex$ pharmacopuncture by EtOH and Hot water extraction inhibited ERK1/2 phosphorylation in LPS induced macrophages. Especially, it has been confirmed that ERK1/2 phosphorylation was effectively inhibited in Hot water extraction. Conclusions : According to the results, $Cinnamomi$ $Cortex$ pharmacopuncture suppresses NO, PGE2 production, COX-2, iNOS expression and ERK1/2 phosphorylation in LPS induced macrophages. It has a potential for treating various inflammatory diseases, and Hot water extraction method could be used more extensively than EtOH extraction method.

• The Korean Journal of Physiology and Pharmacology
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• v.3 no.2
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• pp.127-135
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• 1999

As part of a study on the effects of dexamethasone and dehydroepiandrosterone (DHEA) on the biological roles of astrocytes in brain injury, this study evaluated the effects of dexamethasone and DHEA on the responses of primary cultured rat cortical astrocytes to lipopolysaccharide (LPS) and antimycin A. Dexamethasone decreased spontaneous release of LDH from astrocytes, and the dexamethasone effect was inhibited by DHEA. However, the inhibitory effect of DHEA on the dexamethasone-induced decrease of LDH release was not shown in astrocytes treated with LPS, and antimycin A-induced LDH release was not affected by dexamethasone or DHEA. Unlike dexamethasone, DHEA increased MTT value of astrocytes and also attenuated the antimycin A-induced decrease of MTT value. Glutamine synthetase activity of astrocytes was not affected by DHEA or LPS but increased by dexamethasone, and the dexamethasone- dependent increase was attenuated by DHEA. However, antimycin A markedly decreased glutamine synthetase activity, and the antimycin A effect was not affected by dexamethasone or DHEA. Basal release of $[^3H]arachidonic$ acid from astrocytes was moderately increased by LPS and markedly by antimycin A. Dexamethasone inhibited the basal and LPS-dependent releases of $[^3H]arachidonic$ acid, but neither dexamethasone nor DHEA affected antimycin A-induced $[^3H]arachidonic$ acid release. Basal IL-6 release from astrocytes was not affected by dexamethasone or DHEA but markedly increased by LPS and antimycin A. LPS-induced IL-6 release was attenuated by dexamethasone but was little affected by DHEA, and antimycin A-induced IL-6 release was attenuated by DHEA as well as dexamethasone. At the concentration of dexamethasone and DHEA which does not affect basal NO release from astrocytes, they moderately inhibited LPS-induced NO release but little affected antimycin A-induced decrease of NO release. Taken together, these results suggest that dexamethasone and DHEA, in somewhat different manners, modulate the astrocyte reactivity in brain injuries inhibitorily.

• Molecules and Cells
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• v.45 no.4
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• pp.257-272
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• 2022

In addition to inducing apoptosis, caspase inhibition contributes to necroptosis and/or autophagy depending on the cell type and cellular context. In macrophages, necroptosis can be induced by co-treatment with Toll-like receptor (TLR) ligands (lipopolysaccharide [LPS] for TLR4 and polyinosinic-polycytidylic acid [poly I:C] for TLR3) and a cell-permeable pan-caspase inhibitor zVAD. Here, we elucidated the signaling pathways and molecular mechanisms of cell death. We showed that LPS/zVAD- and poly I:C/zVAD-induced cell death in bone marrow-derived macrophages (BMDMs) was inhibited by receptor-interacting protein kinase 1 (RIP1) inhibitor necrostatin-1 and autophagy inhibitor 3-methyladenine. Electron microscopic images displayed autophagosome/autolysosomes, and immunoblotting data revealed increased LC3II expression. Although zVAD did not affect LPS- or poly I:C-induced activation of IKK, JNK, and p38, it enhanced IRF3 and STAT1 activation as well as type I interferon (IFN) expression. In addition, zVAD inhibited ERK and Akt phosphorylation induced by LPS and poly I:C. Of note, zVAD-induced enhancement of the IRF3/IFN/STAT1 axis was abolished by necrostatin-1, while zVAD-induced inhibition of ERK and Akt was not. Our data further support the involvement of autocrine IFNs action in reactive oxygen species (ROS)-dependent necroptosis, LPS/zVAD-elicited ROS production was inhibited by necrostatin-1, neutralizing antibody of IFN receptor (IFNR) and JAK inhibitor AZD1480. Accordingly, both cell death and ROS production induced by TLR ligands plus zVAD were abrogated in STAT1 knockout macrophages. We conclude that enhanced TRIF-RIP1-dependent autocrine action of IFNβ, rather than inhibition of ERK or Akt, is involved in TLRs/zVAD-induced autophagic and necroptotic cell death via the JAK/STAT1/ROS pathway.

• Journal of Microbiology and Biotechnology
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• v.24 no.3
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• pp.394-400
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• 2014

Avascular necrosis of the femoral head (ANFH) is commonly observed in patients treated with excessive glucocorticoid (GC). Single administration of lipopolysaccharide (LPS) has shown to induce immune stimulatory factors. However, the effect of repeated administration of LPS on GC-induced ANFH has not been studied. Thus, the purpose of this study was (i) to examine the cytokine profile induced by repeated LPS administrations and (ii) to test the effect of repeated LPS treatments on GC-induced ANFH. A mouse necrosis model of ANFH was designed by chronic GC administration with co-treatment of LPS. Mice body weights in the LPS/prednisolone (PDN) co-treated group were lower than that of the untreated control group, but spleen weights were greater than the control group. The levels of IL-6, $TNF{\alpha}$, and IL-33 in the liver and spleen of the LPS/PDN group were lower than the untreated control group, whereas $TNF{\alpha}$ level in the femoral head of the LPS/PDN group increased. Collectively, the effect of repeated LPS on the pathogenesis of GC-induced ANFH was associated with the $TNF{\alpha}$ level in the femoral head, but the pathogenesis did not correspond to cytokine levels in immune tissues.