• Advances in Traditional Medicine
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• v.6 no.3
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• pp.161-166
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• 2006

Chrysanthemum morifolium (CM) is a herb widely used in medicine for the treatment of a variety of diseases. In this study, using mouse peritoneal macrophages, we have examined whether CM affects nitric oxide (NO), tumor necrosis factor $(TNF)-\alpha$ and interleukin (IL)-6 induced interferon $(IFN)-\gamma$ and lipopolysaccharide (LPS). CM inhibits $IFN-\gamma$ and LPS-induced NO in dose dependent manner. We also found that CM inhibits pro-inflammatory cytokine, $TNF-\alpha$ and IL-6. The expression of cyclooxygenase-2 was reduced by CM. These finding means that CM can be used in controlling macrophages-mediated inflammatory disease.

• Natural Product Sciences
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• v.19 no.3
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• pp.201-205
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• 2013

Thirteen phenolic compounds, 1,4-dimethoxybenzene (1), 3,4-dihydroxybenzaldehyde (2), (2E)-3-(4-hydroxy-3,5-dimethoxyphenyl)acrylaldehyde (3), 3,7-dihydroxy-4H-chromen-4-one (4), 2,3-dihydroxy-1-(3,4-dihydroxyphenyl)propan-1-one (5), 4-hydroxy-3-methoxybenzoic acid (6), 4-hydroxy-3,5-dimethoxybenzoic acid (7), methyl 3,4-dihydroxybenzoate (8), 4-hydroxy-3,5-dimethoxybenzaldehyde (9), 3,4-dihydroxybenzoic acid (10), 3-hydroxy-1-(4-hydroxy-3-methoxyphenyl)propan-1-one (11), 2,4,6-trihydroxybenzaldehyde (12) and benzene-1,2,4-triol (13) were isolated from the heartwood of Caesalpinia sappan. Their anti-inflammatory activity was evaluated against LPS-induced NO production in macrophage RAW264.7 cells. Among them, compounds 3 and 8 showed strong inhibitory activities toward the LPS-induced NO production in macrophage RAW264.7 cells with $IC_{50}$ values of 14.5 and 21.5 ${\mu}M$, respectively.

• Journal of Acupuncture Research
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• v.22 no.2
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• pp.111-121
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• 2005

Human placental extract (HPE), which is prepared from the placenta of healthy pregnant females, has been widely used in clinical field. HPE is known to possess anti-inflammatory, anti-viral, anti-oxidative, anti-mutagenic, and analgesic properties. In this study, the effect of HPE against lipopolysaccharide (LPS)-induced inflammation was investigated. From the present results, HPE was shown to suppress prostaglandin E2 synthesis (PGE2) and nitric oxide (NO) production by inhibition on the LPS-stimulated enhancement of the cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expressions in mouse BV2 microglial cells. These results suggest that HPE may offer a valuable mean of therapy for the treatment of brain inflammatory diseases by attenuating LPS-induced PGE2 and NO production.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.151.3-152
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• 2003

Aromatic diamine JSH-21 showed an IC50 value of 9.2 uM with 74.5% inhibition at 30 uM, 53.5% at 10 uM and 24.5% at 3 uM on LPS-induced NO production in murine macrophages Raw 264.7. To examine whether inhibitory effect on NO production by JSH-21 was attributed to influence on iNOS expression, iNOS transcript and protein were analyzed by sequantitative RT-PCR and immunoblot analysis. Consistent with previous result on NO production, treatment of the Raw 264.7 cells with JSH-21 decreased the LPS-induced expression of iNOS transcript and protein in a dose-dependent manner with IC50 values of about 10 uM. (omitted)

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.36 no.1
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• pp.21-39
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• 2023

Objectives : The purpose of this study was to investigate the anti-inflammatory effect of Goihwa-san water extract(GHS) in vitro & in vivo. Methods : In vitro, we evaluated the anti-inflammatory effect of GHS by comparing the Raw 264.7 cells with 10, 30, 100, 300㎍/㎖ of GHS for 1 hour before Lipopolysaccharide(LPS) to the single LPS treated group. We examined the relative cell viability by MTT assay and the relative level of LPS, Loxoribine(LOX), Peptidoglycan(PGN), Flagellin(FLA)-induced NO production by using Griess reagent and measured relative iNOS protein level and COX-2 protein level by using western blot and Image analyzing system. We measured the production of TNF-α, IL-1β, and IL-6 by each ELISA kits and then measured the relative levels of IκBα, p-IκBα in whole-cell lysate fraction and NF-κB in nuclear fraction by using western blot and Image analyzing system. In vivo, we induced the paw edema by subcutaneous injection of 100㎕/rat CA and measured the swelling volume of paw by using a plethysmometer and then measured the relative iNOS protein level by using western blot. Results : As a result, in vitro, LPS, PGN-induced NO production was significantly inhibited by pretreatment with GHS. GHS reduced LPS, PGN-induced iNOS expression, PGN-induced COX-2 expression and LPS-induced production of cytokine(TNF-α, IL-1β, IL-6). Expression of IκBα was increased by pretreatment with GHS 100㎍/㎖. And the expression of p-IκBα and NF-κB were decreased by pretreatment with GHS 100㎍/㎖. In vivo, CA-induced inflammation rat model was used for the evaluation of the anti-inflammatory effect of GHS. 0.3 or 1.0g/kg of GHS significantly reduced the increases of paw swelling and iNOS expression in paw tissues. Conclusions : These results show that GHS can decrease inflammatory response via inhibition of the NF-κB pathway in vitro. And in vivo, the anti-inflammatory effect suggest the clinical basis of GHS for the treatment of inflammatory diseases.

• The Korea Journal of Herbology
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• v.30 no.3
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• pp.69-76
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• 2015

Objectives : The effect of mixture extracted from Bupleuri Radix and Physalidis Herba(BR+RH) on the LPS-induced Depression in rats was investigated. Methods : Rats were administered intragastrically BR+PH after injectio of LPS to induce deprssion. Immobility was examined using Tail Suspension Test(TST), Forced Swimming Test(FST). The level of plasma corticosterone was measured by an Enzyme-Linked Immunosorbent Assay(ELISA) method. The expressions of c-Fos, Corticotropin Releasing Factor(CRF), NADPH-d in the Paraventricular nucleus(PVN) and TH in the Locus coeruleus(LC) were measured by immunohistochemical method. Results : In the effect of BR + PH on TST, immobility was significantly decreased comparing with the LPS group. In FST, immobility was shown decrease tendency in the BR+PH group. The expression of c-Fos in the PVN was significantly decreased at BR + PH400 group, comparing with the LPS group. The expression of CRF in PVN was shown dto have the decrease tendency in the BR+PH group, comparing with the LPS group. The expression of NADPH-d in PVN was not significantly decreased at BR+PH groups, comparing with the LPS group. The expression of TH in the LC was shown to have the decrease tendency at BR + RH groups, but not significantly, comparing with the LPS group. Conclusions : Anti-depressant effect of mixture after extracted from Bupleuri Radix and Physalidis Herba was through the anti-inflammatory effect via inhibition of HPA axis. NO and catecholamine system is not involved.

• Journal of Microbiology and Biotechnology
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• v.31 no.1
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• pp.25-32
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• 2021

Inflammatory reactions activated by lipopolysaccharide (LPS) of gram-negative bacteria can lead to severe septic shock. With the recent emergence of multidrug-resistant gram-negative bacteria and a lack of efficient ways to treat resulting infections, there is a need to develop novel anti-endotoxin agents. Antimicrobial peptides have been noticed as potential therapeutic molecules for bacterial infection and as candidates for new antibiotic drugs. We previously designed the 9-meric antimicrobial peptide Pro9-3 and it showed high antimicrobial activity against gram-negative bacteria. Here, to further examine its potency as an anti-endotoxin agent, we examined the anti-endotoxin activities of Pro9-3 and elucidated its mechanism of action. We performed a dye-leakage experiment and BODIPY-TR cadaverine and limulus amebocyte lysate assays for Pro9-3 as well as its lysine-substituted analogue and their enantiomers. The results confirmed that Pro9-3 targets the bacterial membrane and the arginine residues play key roles in its antimicrobial activity. Pro9-3 showed excellent LPS-neutralizing activity and LPS-binding properties, which were superior to those of other peptides. Saturation transfer difference-nuclear magnetic resonance experiments to explore the interaction between LPS and Pro9-3 revealed that Trp3 and Tlr7 in Pro9-3 are critical for attracting Pro9-3 to the LPS in the gram-negative bacterial membrane. Moreover, the anti-septic effect of Pro9-3 in vivo was investigated using an LPS-induced endotoxemia mouse model, demonstrating its dual activities: antibacterial activity against gram-negative bacteria and immunosuppressive effect preventing LPS-induced endotoxemia. Collectively, these results confirmed the therapeutic potential of Pro9-3 against infection of gram-negative bacteria.

• The Korea Journal of Herbology
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• v.29 no.6
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• pp.85-93
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• 2014

Objectives : We compared with the effects of different parts (root head, root body and hairy root) of Angelica gigas Nakai (Angelicae Gigantis Radix, AG) with on middle cerebral artery occlusion(MCAO)-induced ischemic rats, and on LPS-induced inflammatory response in BV2 microglia. Methods : The 30% ethanol and water extracts of different parts of AG were prepared. Each extract (50 and 100 mg/kg) was administrated intraperitoneally once in MCAO-induced ischemic rats. We measured infarction volumes by TTC staining, and investigated the expression of iNOS, Bax, Bcl-2 and caspase-3 by Western blot. BV2 cells were treated with each extract for 30 min, and then stimulated with LPS. The levels of NO was measured by Griess assay. The expression of iNOS, Cox-2 and proinflammatory cytokines ($TNF-{\alpha}$, $IL-1{\beta}$, and IL-6) were determined RT-PCR and Western blot. The phosphorylation of ERK1/2 and JNK MAPK was determined by Western blot. Results : Among different parts of AG, the 30% ethanol and water extracts of hairy root significantly decreased infarction volume in ischemic brains and inhibited the expression of iNOS, bax and caspase-3. The extracts of hairy root significantly inhibited LPS-induced production of NO, $TNF-{\alpha}$ and IL-6 in BV2 cells, and suppressed the expression of iNOS and COX-2. The hairy root extracts attenuated LPS-induced phosphorylation of ERK1/2 and JNK MAPK in BV2 cells. Conclusions : Our results indicate that the root hairy of AG has a good neuroprotective and anti-inflammatory effects in ischemic stroke compared to other parts.

• Journal of Oriental Neuropsychiatry
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• v.18 no.3
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• pp.55-82
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• 2007

Ohjective: This research investigates the effect of the DJR on Alzheimer's disease. Method: 1.The effects of the DJR extract on IL.-$1{\beta}$, IL-6, TNF-${\alpha}$, cox-2, and NOS-II mRNA of BV2 microglia cell line treated with LPS; 2. the behavior: 3. the infarction area of the hippocampus, and brain tissue injury in Alzheimer's diseased mice induced with ${\beta}$A were investigated. Result: 1. The DJR extract suppressed the expression of IL-$1{\beta}$, IL-6 and TNF-${\alpha}$ mRNA in BV2 microglia cell line treated with LPS. 2. The DJR extract suppressed the expression of IL-$1{\beta}$, IL-6, and TNF-${\alpha}$ protein production in BV2 microglia cell line treated with LPS. 3. For the DJR extract group a significant inhibitory effect on the memory deficit was shown for the mice with Alzheimer's disease induced by .${\beta}$A in the Moms water maze experiment, which measured stop-through latency, and distance movement-through latency. 4. The DJR extract suppressed the over-expression of IL-$1{\beta}$ protein, TNF-${\alpha}$ protein and CD68/CD11b, in the mice with Alzheimer's disease induced by ${\beta}$A 5. The DJR extract reduced the infarction area of hippocampus, and controlled the injury of brain tissue in the mice with Alzheimer's disease induced by ${\beta}$A. 6. The DJR extract reduced the tau protein, GFAP protein, and presenilin1/2 protein (immunohistochemistry) of hippocampus in the mice with Alzheimer's disease induced by ${\beta}$A. Conclusion: These results suggest that the DJR extract may he effective for the prevention and treatment of Alzheimer's disease. Investigation into the clinical use of the DJR extract for Alzheimer's disease of suggested for future research.

• Herbal Formula Science
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• v.25 no.4
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• pp.537-551
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• 2017

Objectives : Jinnoe-san (JNS) is a novel herbal formula consisting of five oriental medicinal herbs including Polygalae Radix, Prunellae Spica, Perillae Herba, Betulae Cortex, and Lonicerae Flos. In this study, we investigated the effects and molecular mechanism of JNS on Parkinson's disease in vitro model. Methods : The effects of JNS on 1-methyl-4-phenylpyridinium ($MPP^+$)-induced cell death in SH-SY5Y cells were evaluated with a cell viability assay, flow cytometry, and western blots analysis. The effects of JNS on lipopolysaccharide (LPS)-stimulated BV2 microglia were determined with a nitric oxide (NO) assay, enzyme linked immunosorbent assays, and western blots analysis. Result : $MPP^+$-induced cell death in SH-SY5Y cells was significantly reduced by JNS pre-treatment in a dose-dependent manner. JNS inhibited the production of reactive oxygen species, mitochondria dysfunction, and apoptosis induced by $MPP^+$ in SH-SY5Y cells. Furthermore, JNS significantly activated Akt and ERK in SH-SY5Y cells and the ability of JNS to prevent mitochondria dysfunction by $MPP^+$ was antagonized by pre-treatment of LY294002 and PD98059, an Akt and ERK inhibitor, respectively. In addition, JNS inhibited LPS-induced NO and $PGE_2$ production as well as iNOS expression and secretion of TNF-${\alpha}$, pro-inflammatory cytokines without affecting the cell viability. JNS also suppressed LPS-induced ERK activation. Conclusions : These results demonstrate that JNS has a protective effect on the dopaminergic neurons against $MPP^+$-induced neurotoxicity and anti-inflammatory effect on the LPS-stimulated microglia. These findings provide evidences for JNS to be considered as a new prescription for treating Parkinson's disease.