• Journal of Physiology & Pathology in Korean Medicine
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• v.25 no.2
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• pp.227-233
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• 2011

Water Fermented and Ethanol Fermented Extracts from Rhei Radix et Rhizoma exhibit potent anti-inflammatory activity with an unknown mechanism. To elucidate the molecular mechanisms of W-FR and E-FR on pharmacological and biochemical actions in inflammation, we examined the effect of W-FR and E-FR on pro-inflammatory mediators in lipopolysaccharide (LPS)-stimulated macrophages. The investigation focused on whether FR inhibited nitric oxide (NO), tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), interleukin-6 (IL-6) and the expressions of iNOS, COX-2 in LPS-stimulated RAW 264.7 cells. We found that FR inhibited LPS-induced NO, TNF-${\alpha}$ and IL-6 productions as well as the expressions of iNOS and COX-2. These results suggest that W-FR and E-FR have inhibitory effects on LPS-induced TNF-${\alpha}$, NO, and IL-6 production, as well as the expressions of iNOS and COX-2 in the murine macrophage.

• The Korean Journal of Physiology and Pharmacology
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• v.25 no.5
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• pp.395-401
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• 2021

Extended inflammation and cytokine production pathogenically contribute to a number of inflammatory disorders. Formosanin C (FC) is the major diosgenin saponin found in herb Paris formosana Hayata (Liliaceae), which has been shown to exert anti-cancer and immunomodulatory functions. In this study, we aimed to investigate anti-inflammatory activity of FC and the underlying molecular mechanism. RAW264.7 macrophages were stimulated with lipopolysaccharide (LPS) or pretreated with FC prior to being stimulated with LPS. Thereafter, the macrophages were subjected to analysis of the expression levels of pro-inflammatory mediators, including nitric oxide (NO), prostaglandin E₂ (PGE), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6, as well as two relevant enzymes, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2). The analysis revealed that FC administration blunted LPS-induced production of NO and PGE in a dose-dependent manner, while the expression of iNOS and COX-2 at both mRNA and protein levels was inhibited in LPS-stimulated macrophages pre-treated with FC. Moreover, LPS stimulation upregulated mRNA expression and medium release of TNF-α, IL-1β, and IL-6, whereas this effect was blocked upon FC pre-administration. Mechanistic studies showed that inhibitory effects of FC on LPS-induced inflammation were associated with a downregulation of IκB kinase, IκB, and p65/NF-κB pathway. Taken together, these data suggest that FC possesses an inflammation-suppressing activity, thus being a potential agent for the treatment of inflammation-associated disorders.

• Microbiology and Biotechnology Letters
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• v.44 no.3
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• pp.268-277
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• 2016

This study aimed to investigate the anti-inflammatory effect of the ethanol extract from Chondrus ocellatus Holmes (COHEE) in RAW 264.7 cells and in a mouse ear edema model, by measuring the production of lipopolysaccharide-induced inflammatory response mediators. There were no cytotoxic effects on the proliferation of macrophages treated with COHEE compared with the control. COHEE inhibited the production of nitric oxide and pro-inflammatory cytokines [interleukin (IL)-6, tumor necrosis factor-α, and IL-1β]. The extract also reduced the expression of inducible nitric oxide synthase, cyclooxygenase-2, nuclear factor-κB p65, and phosphorylated mitogen-activated protein kinase in a dose-dependent manner. In the croton-oil-induced ear edema model, COHEE decreased the formation of mouse ear edema at the highest dose compared with the control, and histological analysis revealed that the epidermal/dermal tissue thickness and mast cell numbers were reduced. Therefore, these results suggest that COHEE may be a promising topical anti-inflammatory therapeutic material through its action of modulating NF-κB and the MAPK signaling pathway.

• Korean Journal of Plant Resources
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• v.31 no.5
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• pp.466-477
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• 2018

In this study, the anti-inflammatory activities of the extracts of different parts of Hovenia dulcis such as leaves, stems, and roots were investigated. Among them, the roots extract (RE) showed the most potent suppressive effect against pro-inflammatory mediators in LPS-stimulated mouse macrophage cells. RE induced dose-dependent reduction of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) and concomitantly reduced the production of NO and $PGE_2$. Additionally, pre-treatment with RE significantly suppressed the production of inflammatory cytokines, such as tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$), interleukin $(IL)-1{\beta}$, and IL-6, as well as mRNA levels. Moreover, phosphorylation of mitogen-activated protein kinases (MAPKs) and nuclear translocation of nuclear factor-kappa B (NF-kB) were also strongly attenuated by RE in RAW264.7 cell. Furthermore, RE induced HO-1 expression through nuclear translocation of nuclear factor E2-related factor 2 (Nrf2) and increase HO-1 activity in RAW264.7 macrophages. Therefore, these results indicate that RE strongly inhibits LPS-induced inflammatory responses by blocking NF-kB activation, inhibiting MAPKs phosphorylation, and enhancing HO-1 expression in macrophages, suggesting that RE of H. dulicis and a major component, 27-O-protocatechuoylbetulinic acid could be applied as a valuable natural anti-inflammatory material.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.6
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• pp.1622-1627
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• 2004

Nephrite has been widely used as a medicinal mineral resource to treat a numerous chronic diseases and to replenish vital essence and blood in the Korean traditional medicine. However, as of yet, there is little understanding of the pharmacological and biochemical mechanisms of its therapeutic effects as regards anti-inflammation. We therefore examined whether nephrite represses the expression of major inflammation mediators, such as interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2), in LPS-stimulated murine macrophage cell line, RAW264.7 by using RT-PCR. The powder suspension and water extracts of nephrite significantly inhibited the mRNA expression of the mediators, despite a little toxic effects on growth of RAW 264.7 cells within the concentration range tested. These experimental results suggested that the nephrite can be utilized as a functional mineral exerting the anti-inflammation medicinal effect.

• BMB Reports
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• v.55 no.8
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• pp.370-379
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• 2022

Human pregnancy is a delicate and complex process where multiorgan interactions between two independent systems, the mother, and her fetus, maintain pregnancy. Intercellular interactions that can define homeostasis at the various cellular level between the two systems allow uninterrupted fetal growth and development until delivery. Interactions are needed for tissue remodeling during pregnancy at both fetal and maternal tissue layers. One of the mechanisms that help tissue remodeling is via cellular transitions where epithelial cells undergo a cyclic transition from epithelial to mesenchymal (EMT) and back from mesenchymal to epithelial (MET). Two major pregnancy-associated tissue systems that use EMT, and MET are the fetal membrane (amniochorion) amnion epithelial layer and cervical epithelial cells and will be reviewed here. EMT is often associated with localized inflammation, and it is a well-balanced process to facilitate tissue remodeling. Cyclic transition processes are important because a terminal state or the static state of EMT can cause accumulation of proinflammatory mesenchymal cells in the matrix regions of these tissues and increase localized inflammation that can cause tissue damage. Interactions that determine homeostasis are often controlled by both endocrine and paracrine mediators. Pregnancy maintenance hormone progesterone and its receptors are critical for maintaining the balance between EMT and MET. Increased intrauterine oxidative stress at term can force a static (terminal) EMT and increase inflammation that are physiologic processes that destabilize homeostasis that maintain pregnancy to promote labor and delivery of the fetus. However, conditions that can produce an untimely increase in EMT and inflammation can be pathologic. These tissue damages are often associated with adverse pregnancy complications such as preterm prelabor rupture of the membranes (pPROM) and spontaneous preterm birth (PTB). Therefore, an understanding of the biomolecular processes that maintain cyclic EMT-MET is critical to reducing the risk of pPROM and PTB. Extracellular vesicles (exosomes of 40-160 nm) that can carry various cargo are involved in cellular transitions as paracrine mediators. Exosomes can carry a variety of biomolecules as cargo. Studies specifically using exosomes from cells undergone EMT can carry a pro-inflammatory cargo and in a paracrine fashion can modify the neighboring tissue environment to cause enhancement of uterine inflammation.

• The Korea Journal of Herbology
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• v.31 no.6
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• pp.1-9
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• 2016

Objectives : Gamisoyosan (GMS) is a useful prescription for treating insomnia, dysmenorrhea and infertility induced by a stress. Also, GMS has been used traditionally to improve systemic circulation and biological energy production. The purpose of this study was to assess the anti-oxidant activity and anti-inflammatory effects of Gamisoyosan Formulation (Soft extract, GMS-SE). Methods : The biological activities such as anti-oxidant and anti-inflammatory effects were measured through cell line-based in vitro assay. We investigated the anti-oxidant properties of GMS-SE on the 1,1-diphenyl-2-picryhydrazyl (DPPH) radical, contents of total flavonoid and polyphenol. GMS-SE compared to butyl hydroxy anizole (BHA). Furthermore, based on this result the anti-inflammatory effects of GMS-SE have verified by mechanism from LPS- treated Raw264.7 macrophages. Results : The anti-oxidant activities of GMS-SE increased markedly, in a dose-dependent manner. The GMS-SE showed significant scavenging activity (GMS-SE $500{\mu}g/m{\ell}$ : $32.77{\pm}1.65%$, GMS-SE $1000{\mu}g/m{\ell}$ : $45.06{\pm}1.04%$ and BHA $100{\mu}g/m{\ell}$ : $39.25{\pm}2.41%$ for DPPH assay). and, The total phenolic compound and flavonoids contents of GMS-SE were $73.93{\pm}6.87{\mu}g/mg$ and $698.75{\pm}6.78{\mu}g/mg$. GMS-SE which is LPS has diminished in the LPS-induced release of inflammatory mediators (NO, iNOS, COX2 and PGE2) and pro-inflammatory cytokines (TNF-${\alpha}$, IL-6 and IL-$1{\beta}$) from the RAW264.7 macrophages. Moreover, GMS-SE inhibited the activation of phosphorylation of p38 and ERK MAPKs by induced LPS. Conclusion : The present results indicate that GMS-SE has an anti-oxidant and anti-inflammatory properties, therefore may be beneficial in diseases which related to oxidative stress-mediated inflammatory disorders.

• Herbal Formula Science
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• v.27 no.2
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• pp.101-120
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• 2019

PURPOSE : Euonymi Lignum Suberalatum (EL) is the stem fin of Euonymi alatus. In traditional Korean medicine, EL is used for treatment of uterine bleeding, metritis and static blood. Recently, many studies have reported several pharmacological effects of EL including anticancer, antimicrobial, antidiabetic activity, and anti-oxidative stress. However, the mechanisms underlying anti-inflammatory effects by the EL is not established. METHODS : To investigate anti-inflammatory effects of Euonymi Lignum Suberalatum Water (ELWE), Raw 264.7 cells were pre-treated with $10-300{\mu}g/mL$ of ELWE, and then exposed to $1{\mu}g/mL$ of LPS. Levels of NO, IL-6, $IL-1{\beta}$ and $TNF-{\alpha}$ were detected by ELISA kit. Expression of pro-inflammatory proteins were determined by immunoblot analysis. To evaluate the anti-inflammatory effect in vivo, rat paw edema volume, and expressions of COX-2 and iNOS proteins in carrageenan (CA)-induced rat paw edema model. RESULTS : NO production activated by LPS, was decreased by $30-300{\mu}g/mL$ of ELWE. Production of inflammatory mediators such as $TNF-{\alpha}$, ILs, $PGE_2$ were decreased by ELWE 100 and $300{\mu}g/mL$. In addition, ELWE reduced LPS-mediated iNOS and COX-2 expression. Moreover, ELWE increased $I-{\kappa}B{\alpha}$ expression in cytoplasm and decreased $NF-{\kappa}B$ expression in nucleus. In vivo study, ELWE reduced the increases of paw swelling, and expression of iNOS and COX-2 proteins in paw edema induced by CA injection. CONCLUSION : The results indicate that ELWE could inhibit the acute inflammatory response, via modulation of $NF-{\kappa}B$ activation. Furthermore, inhibition of rat paw edema induced by CA is considered as clear evidence that ELWE may be a useful source to treat acute inflammation.

• Korean Journal of Plant Resources
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• v.34 no.1
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• pp.31-36
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• 2021

Berchemia berchemiaefolia (Makino) Koidz. is found not only in korea, but also in japan and is known as a rare plant all over the world. In this study, we evaluated anti-inflammatory effect of B. berchemiaefolia (Makino) Koidz. leaves (BBK-L) in LPS-stimulated RAW264.7 cells. BBK-L inhibited the generation of NO through the suppression of iNOS experession. BBK-L attenuated the expression of iNOS, COX-2, TNF-α, IL-1β, IL-6 induced by LPS. BBK-L decreased LPS-mediated IκB-α degradation inhibite which resulted in the inhibition of NF-κB activation in RAW264.7 cells. In addition, BBK-L suppressed ERK1/2, JNK phosphorylation induced by LPS. BBK-L showed anti-inflammatory effect through blocking the generation of the inflammatory mediators such as NO, iNOS, COX-2, TNF-α, IL-1β, IL-6 via the inhibiting of NF-κB and MAPK signaling activation. These results suggests that BBK-L may have great potential for the development of anti-inflammatory drug to treat acute and chronic inflammatory disorders.

• Biomedical Science Letters
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• v.23 no.4
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• pp.411-415
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• 2017

To evaluate the protective effects of Plantago Major extract (PME) in stimulated BV-2 microglial cells and its anti-oxidant properties, cell viability assessment was performed by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Lipopolysaccharide (LPS) was used to activate BV-2 microglia. Nitric oxide (NO) levels were measured using Griess assay. Tumor necrosis factor-alpha (TNF-${\alpha}$) production was evaluated by enzyme-linked immunosorbent assay (ELISA). Antioxidant properties were evaluated by 1, 1-diphenyl-2-picryl-hydrazyl (DPPH) radical scavenging assay. LPS-activated excessive release of NO in BV-2 cells was significantly inhibited by PME (P < 0.001 at $100{\mu}g/mL$). PME also scavenged DPPH radicals in a dose-dependent manner (P < 0.05 at $10{\mu}g/mL$ and P < 0.001 at $20{\sim}200{\mu}g/mL$). These results indicate that PME attenuated neuroinflammatory responses in LPS-activated BV-2 microglia by inhibiting excessive production of pro-inflammatory mediators such as NO and TNF-${\alpha}$. The anti-neuroinflammatory potential of PME may be related to its strong antioxidant properties.