• Journal of Nutrition and Health
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• v.52 no.2
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• pp.129-138
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• 2019

Purpose: Medicinal herbs have recently attracted attention as health beneficial foods and source materials for drug development. Recent studies have demonstrated that extracts of Lycium's fruits and roots have a range of physiologically active substances. The extract of Lycium's leaves has been reported to have excellent anti-oxidant and anti-microbial activity, but its anti-inflammatory efficacy is not known. The chlorophyll present in the leaves can act as an anti-oxidant or pro-oxidant depending on the presence of light. Therefore, this study analyzed the anti-inflammatory effects of Lycium's fruit extract (LFE), leaf extract (LLE), and leaf extract with chlorophyll removal (LLE with CR). Methods: This study examined the inhibitory effects of LFE, LLE, and LLE with CR on pro-inflammatory mediator production as well as on the expression of iNOS and COX-2 in lipopolysaccharide (LPS)-stimulated RAW264.7 cells and BALB/c mice. Results: LFE, LLE, and LLE with CR inhibited the production of pro-inflammatory mediators (NO, $TNF-{\alpha}$, IL-6, and $IL-1{\beta}$) and the expression of iNOS and COX-2 in LPS-stimulated RAW 264.7 cells in a dose-dependent manner. Furthermore, the administration of LLE and LLE with CR inhibited the serum pro-inflammatory cytokine levels and suppressed DNA damage in BALB/c mice. In particular, LLE with CR exhibited the highest anti-inflammatory activity. Conclusion: These results suggest that the fruit and leaves of Lycium are potential therapeutic agents against inflammation.

• Journal of Life Science
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• v.23 no.6
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• pp.736-742
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• 2013

Achyranthoside E dimethyl ester (AEDE) is an oleanolic acid glycoside from Achyranthes japonica. In this study, we investigated the effects of AEDE on nitric oxide (NO) production and underlying molecular mechanisms in lipopolysaccharide (LPS)-stimulated macrophages. AEDE inhibited LPS-induced NO secretion as well as inducible NO synthase (iNOS) expression, without affecting cell viability. Further study demonstrated that AEDE induced heme oxygenase-1 (HO-1) gene expression. In addition, the inhibitory effects of AEDE on iNOS expression were abrogated by small interfering RNA-mediated knock-down of HO-1. Moreover, AEDE induced nuclear translocation of nuclear factor E2-related factor 2 (Nrf2), a transcription factor that regulates HO-1 expression. AEDE-induced expression of HO-1 was inhibited by inhibitors of phosphatidylinositol 3-kinase (PI-3K) and extracellular signal regulated kinase (ERK1/2). AEDE phosphorylated Akt and ERK1/2 as well. Therefore, these results suggest that AEDE suppresses the production of pro-inflammatory mediator such as NO by inducing HO-1 expression via PI-3K/Akt/ERK-Nrf2 signaling. These findings provide the scientific rationale for anti-inflammatory therapeutic use of AEDE.

• Journal of Life Science
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• v.16 no.3 s.76
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• pp.500-504
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• 2006

Haptoglobin (Hp) is an acute phase protein, and its plasma level increases consistently in response to inflammation. To investigate the biological role of Hp in lung epithelial cells, the gene expressions of cyclooxygenase-2 (COX-2) and inflammatory cytokines were analyzed using human Hp gene-transfected A549 cells. Western blot analysis showed that COX-2 expression was markedly increased in Hp DNA-transfected cells (stable transfection and transient transfection) compared with that in vehicle DNA-transfected cells. When the Hp-expressing cells were treated with $1{\mu}g/ml$ of LPS or 100 U/ml of $IL-1{\beta}$ for 24 hr, the COX-2 expression was synergistically up-regulated. ACP-based PCR data demonstrated the Hp decreased SPARC expression, but increased IL-4 and S100AI expressions. These findings suggest that the Hp acts as a pro-inflammatory mediator in lung inflammation.

• Journal of Life Science
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• v.25 no.9
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• pp.976-983
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• 2015

Achyranthoside C dimethyl ester (ACDE) is an oleanolic acid glycoside from Achyranthes japonica which has been used in traditional medicine for the treatment of edema and arthritis. In this study, we investigated the anti-inflammatory effects of ACDE in RAW264.7 macrophages. ACDE significantly induced heme oxygenase-1 (HO-1) gene expression in RAW264.7 cells, while ACDE improved LPS-induced toxicity of cells. And ACDE induced nuclear translocation of nuclear factor E2-related factor 2 (Nrf2), a transcription factor that regulates HO-1 expression. Further study demonstrated that ACDE-induced expression of HO-1 was inhibited by inhibitors of phosphatidylinositol 3-kinase (PI-3K) (LY294002), c-Jun kinase (JNK) (SP600125), extracellular signal regulated kinase (ERK) (PD98059) and p38 kinase (SB203580). Moreover, ACDE phosphorylated Akt, JNK, ERK, and p38 MAPK. In addition, ACDE inhibited LPS-induced NO secretion as well as inducible NO synthase (iNOS) expression in a dose-dependent manner. The inhibitory effects of ACDE on iNOS expression were abrogated by small interfering RNA (siRNA)-mediated knock-down of HO-1. Therefore, these results suggest that ACDE suppresses the production of pro-inflammatory mediator such as NO by inducing HO-1 expression via PI-3K/Akt/MAPK-Nrf2 signaling pathway. These findings could help us to understand the active principle included in the roots of A. japonica and the molecular mechanisms underlying anti-inflammatory action of ACDE.

• Journal of Life Science
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• v.27 no.1
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• pp.8-14
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• 2017

Died Gardenia jasminoides fruit is used as a dye in the food and clothes industries in Asia. The present study investigated the anti-inflammatory effects of aqueous extract of G. jasminoides fruits (GJ) in BV-2 microglial cells. GJ inhibited lipopolysaccharide-induced nitric oxide (NO) secretion, inducible nitric oxide synthase (iNOS) expression, and reactive oxygen species production, without affecting cell viability. Furthermore, GJ increased the expression of heme oxygenase-1 (HO-1) in a dose-dependent manner. Moreover, the inhibitory effect of GJ on iNOS expression was abrogated by small interfering RNA-mediated knock-down of HO-1. In addition, GJ induced nuclear translocation of nuclear factor E2-related factor 2 (Nrf2), a transcription factor that regulates HO-1 expression. GJ-mediated expression of HO-1 was suppressed by LY294002, a phosphoinositide 3-kinase (PI-3K) inhibitor, and SB203580, a p38 kinase inhibitor, but not by the extracellular signal-regulated kinase (ERK) inhibitor PD98059 or c-Jun N-terminal kinase (JNK) inhibitor SP600125. GJ also enhanced the phosphorylation of Akt and p38. These results suggest that GJ suppresses the production of NO, a pro-inflammatory mediator, by inducing HO-1 expression via PI-3K/Akt/p38 signaling. These findings illustrate a novel molecular mechanism by which extract from G. jasminoides fruits inhibits neuroinflammation.

• Natural Product Sciences
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• v.5 no.3
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• pp.113-120
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• 1999

Nitric oxide (NO) is a free radical synthesized from L-arginine by nitric oxide synthase (NOS). It is believed that NO is an important mediator in numerous physiological and inflammatory responses. Particularly, a large amount of NO released from the inducible nitric oxide synthase (iNOS) is mostly associated with inflammatory processes. Overproduction of NO in these processes including sepsis and autoimmune diseases can have deleterious consequences and pathophysiologic relevance. Therefore, for the discovery of new inhibitory agents against iNOS activity, we have evaluated about 100 kinds of natural products after partition into three layers (n-hexane, ethyl acetate and aqueous) from 100% methanol extracts to study inhibitory effects on iNOS activity induced by lipopolysaccharide (LPS) in RAW264.7 cells culture system. As a positive control, curcumin, which is known as an anti-tumor promoter, anti-inflammatory agent as an iNOS inhibitor, was used and showed the dose-dependent inhibitory effect $(IC_{50},\;2.5\;{\mu}g/ml)$. Among tested fractions, the n-hexane fraction of Cimicifuga heracleifolia $(IC_{50}:\;9.65\;{\mu}g/ml)$, Forsythiae fructus $(IC_{50}:\;6.36\;{\mu}g/ml)$, Saposhnikovia divaricata $(IC_{50}:\;5.92\;{\mu}g/ml)$, and the ethyl acetate fraction of Chrysanthemum sibiricum $(IC_{50}:\;2.56\;{\mu}g/ml)$, Gastrodia elata $(IC_{50}:\;3.46\;{\mu}g/ml)$, and the aqueous fraction of Dianthus chinensis $(IC_{50}:\;6.73\;{\mu}g/ml)$, Euonymus alatus $(IC_{50}:\;6.78\;{\mu}g/ml)$, Mechania urticifoloria $(IC_{50}:\;8.01\;{\mu}g/ml)$ showed strong inhibitory activity against LPS-stimulated iNOS. Especially, the ethyl acetate fraction of Chrysanthemum sibiricum $(IC_{50}:\;2.56\;{\mu}g/ml)$, which exhibited the strongest inhibition against iNOS, was fractionated with silica-gel column chromatography. These subfractions exhibited dose-dependent inhibition against iNOS activity in the range of $2.59-5.6\;{\mu}g/ml$ except for fraction No. 3, 4, 5, 6, 8, 9, and 16. Our study shows that Chrysanthemum sibiricum has the strongest inhibitory effect against iNOS activity and has similar effect to curcumin. Therefore, further studies for the identification of active principles from Chrysanthemum sibiricum and investigation for the mechanism of the inhibition of iNOS by active principles will be performed.

• Journal of the Korean Society of Food Science and Nutrition
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• v.41 no.4
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• pp.456-461
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• 2012

The leaves of $Stevia$ $rebaudiana$ are well-known in Japan, Korea, and China as a natural sweetener. Medicinal uses of this plant originated in Paraguay and Brazil in the form of aqueous decoctions of the leaves used as a contraceptive agent and for the treatment of hyperglycemia. In the present study, the antioxidant, anti-hypertension, and anti-inflammatory activities of $S.$ $rebaudiana$ extracts are investigated for their use in food. The biologically-active compound was isolated and purified from $S.$ $rebaudiana$. The isolated compound was identified as austroinulin ($C_{20}H_{34}O_3$; molecular weight 322) by mass, IR spectrophotometry, 1D, and 2D-NMR. Austroinulin was characterized as a diterpenoid possessing a 3-methylpenta-2,4-dienyl at C-9. When subjected to an inflammatory mediator inhibitory assay from lipopolysaccharide (LPS)-activated macrophages, the austroinulin inhibited the enhanced production of nitric oxide (NO) and inducible nitric oxide synthase (iNOS) expression (10 ${\mu}g$/mL＝67.9 and 45.1%, respectively). This was significant and dose-dependent. The results suggest that austroinulin from $S.$ $rebaudiana$ inhibited the NO and iNOS in RAW 264.7 cells.

• Journal of Chest Surgery
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• v.34 no.10
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• pp.745-753
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• 2001

capillary leak syndrome and organ dysfunction in infants. Removing harmful cytokines and complement anaphylatoxins after cardiopulmonary bypass may attenuate this response. This study was conducted to see if the modified ultrafiltration and postoperative peritoneal dialysis can reduce plasma inflammatory mediators in pediatric cardiac surgery. Material and Method: 30 infants (age 1.1 to 12.6 months) who underwent closures of ventricular septal defect using cardiopulmonary bypass (CPB) were enrolled in this study. These patients were divided into three groups; 10 patients selected randomly underwent modified ultrafiltration (Group U), 10 with small body weights ($\leq$5 kg) received postoperative peritoneal dialysis (Group P), and 10 patients did not undergo modified ultrafiltration nor receivcd peritoneal dialysis (Group C). Serum samples were obtained before and after CPB, and after peritoneal dialysis. Effluents sample were also obtained after modified ultrafiltration or peritoneal dialysis. C3a and interleukin-6 (IL-6) were measured by radioimmunoassay and enzyme-linked immunosorbent assay respectively. Result: There was no differences in CPB time, aortic cross-clamping title, and lowest temperature during CPB. The effluents of peritoneal dialysis contained significant amount of C3a and IL-6, but there was no definitive decrease of serum concentration of C3a and IL-6. The effluents of modified ultrafiltration had some amount of C3a and negligible IL-6, and there was no decrease of serum concentration of these (actors. Conclusion: The effluents of peritoneal dialysis contained significant amount of proinflammatory cytokine, IL-6 and complement, C3a. However this study failed to elucidate the decrease in serum levels of these factors. The modified ultrafiltration also was not able to reduce the serum levels of C3a or IL-6 in our study as well.

• The korean journal of orthodontics
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• v.28 no.4 s.69
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• pp.611-626
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• 1998

Cytokines are intercellular peptide mediators that regulate homeostasis and host defense reactions in living body. Of the diversity of cytokines in terms of biological accomplishment, interleukin $1-{\beta}$($IL-1{\beta}$) and tumor necrosis factor(TNF) are the most conspicuous cytokines with a wide variety of effects on cells involved in inflammatory and immune responses, and likely to be involved in the inflammatory pathogenesis of oral tissue as well. The present study was designed to explicate the role of $IL-1{\beta}$ on inflammatory revelation of oral tissues in mice biochemically. In the Induced arthritis by injection of 10${\mu}g$ LPS shown the relaese of 0.93 ${\mu}g$ $IL-1{\beta}$/joint with a peak at at 4-5 h. and diminished at 24t and the release of $TNF_{\alpha}$ of 1.25 ${\mu}g$/joint with a peak at 2-3h and diminished at 6h. After injection of th $IL-1{\beta}$ into the joint, the mumber of leucocytes proliferated with a peak at 4-5h and diminished at 36h and the loss of proteoglycan showed with maximum at 15-30h. After injection of $IL-1{\beta}$ into the oral tissue, cycloosygenase metabolites ($PGE_2$) accumulated in the oral tissue with dose dependant. These elucidated $IL-1{\beta}$ to be inflammatory mediator in the early phase of its pathogenesis. Intraoral injection of recombinant $IL-1{\beta}$ induced the proliferation of leukocytes in situ. $IL-1{\beta}$ took an pertinent part in the development of inflammation and the succession of cellular infiltration. The results exemplify that $IL-1{\beta}$ plays a significant role in mediating inflammatory response induced by LPS in oral tissue, the inflammatory response is regulated by $IL-1{\beta}$ at an acute phase of pathogenesis.

• Tuberculosis and Respiratory Diseases
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• v.67 no.1
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• pp.14-20
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• 2009

Background: The pathophysiologic mechanisms of radiation-induced lung injury should be elucidated to enhance the therapeutic efficacy of radiotherapy and to manage patients exposed to serious radiation by accident. It has been suggested that pro-inflammatory cytokines play an important role in radiation-induced effect on the lung. This study was aimed to investigate changes in pro-inflammatory cytokines such as TNF-$\alpha$, MIP-2, IL-1$\beta$ and HMGB1, a newly recognized inflammatory mediator. Methods: The chests of BALB/c mice were selectively irradiated with single fraction of 20 Gy and then sacrificed at indicated times. Pathologic changes in the lung were examined after H&E staining. The expression level of pro-inflammatory cytokines was evaluated by ELISA kits in lung homogenate and in serum. Results: Radiation induced inflammatory changes and mild fibrosis in lung. Biphasic increase of TNF-$\alpha$ and IL-1$\beta$ was found in lung homogenate at 4 hours and at 3 weeks after radiation. The elevation in the second phase tended to be more intense. However, there was no similar change in serum. MIP-2 level was slightly increased in lung homogenate at 4 hours, but not at 3 weeks. HMGB1 was increased at 3 weeks in serum while there was no significant change in lung homogenate. Conclusion: Radiation induced a biphasic increase in TNF-$\alpha$ and IL-1$\beta$. The effective control of second phase cytokine elevation should contribute to preventing severe lung fibrosis caused by radiation.