• The Journal of Pediatrics of Korean Medicine
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• v.28 no.3
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• pp.47-58
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• 2014

Objectives GyejigaChulBuTang (GCBT) is a prescription used to treat acute and chronic arthritis in Korea, China, and Japan. This study assessed the anti-inflammatory and anti-oxidant activities of GCBT on lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells. Methods Raw264.7 cells were pretreated with or without GCBT for 1 hour prior to incubation with LPS. Anti-inflammatory activity of GCBT was evaluated with reference to gene expression and production levels of proinflammatory cytokines ($TNF{\alpha}$, IL-$1{\beta}$, IL-6, GM-CSF and $INF{\gamma}$) and inflammatory mediators (iNOS, COX-2, NO and $PGE_2$). In addition, intracellular ROS generation and signal transduction of MAPK family, PI3K/Akt and $I{\kappa}B{\alpha}/NF{\kappa}B$ was investigated. Results Prior treatment with GCBT inhibited elevation of $TNF{\alpha}$, IL-$1{\beta}$, IL-6, GM-CSF, $INF{\gamma}$, NO and $PGE_2$, together with their cognate mRNAs in a dose-dependent manner. Intracellular ROS contents were similarly reduced. These effects were due to inhibition of LPS-induced phosphorylation of MAPK family, PI3K/Akt and $I{\kappa}B{\alpha}$ as well as nuclear translocation of $NF{\kappa}B$. Conclusions GCBT suppresses pro-inflammatory mediators. GCBT has potential in the treatment of juvenile rheumatoid arthritis associated with inflammation.

• Korean Journal of Pharmacognosy
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• v.49 no.4
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• pp.305-311
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• 2018

Osteoarthritis (OA) is the most common form of joint disease, characterized by articular cartilage, osteonecrosis, and osteochondral bone erosion. It is an early, progressive disease that combines joint stiffness and joint pain and reduces cartilage function and condition. Interleukin-1 beta ($IL-1{\beta}$) is thought to be important to the pathogenesis of OA and significantly increases the expression of matrix metalloproteinases (MMPs), which play an important role in cartilage degradation in OA. Sparassis crispa (Wulf.) is an edible / medicinal mushroom that has been reported to variety of biological activities. In this study, investigated the Anti-inflammatory effect of Sparassis crispa (Wulf.) ethanol extract (SCE) on $IL-1{\beta}$ stimulated SW1353 chondrocytes. SCE decreased the expression and activity of MMPs by $IL-1{\beta}$ and decreased the levels of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) associated with the inhibition of prostaglandin E2($PGE_2$) in $IL-1{\beta}$ stimulated SW-1353 chondrocytes. In addition, SCE inhibits the expression of MAPK (mitogen-activated protein kinase) and $NF-{\kappa}B$ (nuclear factor-kappa B) signaling in $IL-1{\beta}$ stimulated SW-1353 cells, and SCE inhibits the production of reactive oxygen species (ROS) through heme oxygenase-1 (HO-1) expression. Thus, it is suggested that SCE has a potential as an anti-inflammatory agent in osteoarthritis treatments.

• Journal of Life Science
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• v.24 no.6
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• pp.664-670
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• 2014

In the present study, we investigate the role of V. vulnificus in promoting the inflammation of mouse ileal ephitelium and its related signaling pathways. ICR mice were infected orally with V. vulnificus ($1{\times}10^9CFU$) for 16 h as a representative model of food-borne infection. To find the major portal of entry of V. vulnificus in mouse intestine, we have measured the levels of bacterial colonization in small intestine, colon, spleen, and liver. V. vulnificus appeared to colonize in intestine and colon in the order of ileum >> jejunum> colon, but lack in the duodenum, spleen, and liver. V. vulnificus in ileum caused severe necrotizing enteritis and showed shortened villi heights accompanied by an expanded width and inflammation, compared with the control mice. V. vulnificus induced ileal epithelium inflammation by activating phosphorylation of PKC and membrane translocation of $PKC{\alpha}$. V. vulnificus induced the phosphorylation of ERK and JNK, but did not affect p38 MAPK phosphorylation. Notably, V. vulnificus stimulated the I-${\kappa}B$-dependent phosphorylation of NF-${\kappa}B$ in mouse ileal epithelium. Finally, the ileal infection of V. vulnificus resulted in a significant increase in expression of proinflammatory cytokines and Toll-like receptors, respectively, compared to the control. Collectively, our results indicate that V. vulnificus induces ileal epithelium inflammation by increasing NF-${\kappa}B$ phosphorylation via activation of PKC, ERK, and JNK, which is critical for host defense mechanism in food-borne infection by V. vulnificus.

• 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.

• Journal of Life Science
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• v.33 no.6
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• pp.463-470
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• 2023

Desmarestia tabacoides Okamura is a brown macroalgae that is found worldwide. Although several genera of Desmarestia have been reported as having anti-tumorigenic, anti-melanogenic, and photoprotective properties, the anti-inflammatory activity of D. tabacoides Okamura has not yet been evaluated. In this study, we analyzed the anti-inflammatory mechanisms of D. tabacoides Okamura ethanol extract (DTEE) via the inhibition of nitric oxide (NO) and prostaglandin (PG) E₂ production and the expression of their corresponding enzymes, inducible NO synthase (iNOS), and cyclooxygenase (COX)-2. In addition, their upstream signaling molecules were evaluated by Western blot analysis, such as nuclear factor (NF)-κB, mitogen-activated protein kinase (MAPK), and phosphoinositide-3-kinase (PI3K)/Akt, in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. The DTEE treatment significantly inhibited LPS-induced NO and PGE₂ production as well as the expression of their corresponding enzymes, iNOS, and COX-2 without cytotoxicity. The stimulated transcription factor NF-κB and upstream signaling molecules extracellular signal-regulated kinase (ERK), c-Jun NH₂-terminal kinase (JNK), and p38 were attenuated by the DTEE treatment, which was statistically significant, while Akt did not provide any inhibitory effect. Moreover, the DTEE treatment significantly mitigated the LPS-activated adaptor molecules, toll-like receptor 4 (TLR4), and myeloid differentiation primary response 88 (MyD88) in the RAW 264.7 cells. These results suggest that DTEE attenuates TLR4-mediated inflammatory responses by inhibiting NF-κB activation and suppressing MAPK phosphorylation in LPS-stimulated RAW 264.7 cells.

• Korean Journal of Pharmacognosy
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• v.46 no.3
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• pp.195-202
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• 2015

Cnidium monnieri (L). Cussion is used as a tonic agent in traditional oriental medicine. However, the molecular mechanism of mast cell-mediated anti-inflammatory modulation has not been fully understood. The aim of the present study was to demonstrate the effects of Cnidium monnieri (L). Cussion eathyl acetate fraction on the expression of pro-inflammatory cytokines, as well as to elucidate its mechanism of action in the human mast cell line (HMC-1). Cells were stimulated with phorbol 12-myristate 13-acetate (PMA) plus A23187 in the presence or absence of Cnidium monnieri (L). Cussion eathyl acetate fraction. Cnidium monnieri (L). Cussion eathyl acetate fraction significantly inhibited the PMA plus A23187-induction of inflammatory cytokines such as tumor necrosis factor (TNF)-$\alpha$, interleukin (IL)-6 and IL-8. Moreover, EtOAc fraction attenuated cyclooxygenase (COX)-2 expression. In activated HMC-1 cells, phosphorylation of extra-signal response kinase (ERK) 1/2 decreased after treatment with EtOAc fraction. Moreover EtOAc fraction inhibited PMA plus A23187-induced nuclear factor (NF)-${\kappa}B$ activation, $I{\kappa}B$ degradation. EtOAc fraction suppressed the expression of TNF-$\alpha$, IL-6, IL-8 through a decrease in the ERK 1/2, as well as activation of NF-${\kappa}B$. These results indicated that Cnidium monnieri (L). Cussion EtOAc fraction exerted a regulatory effect on inflammatory reactions mediated by mast cells.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2018.04a
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• pp.89-89
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• 2018

Abeliophyllum distichum is a medicinal plant used in regional traditional medicine to relieve pain in inflammatory processes. In this study, anti-inflammatory effects of Abeliophyllum distichum stem (ADS) ethyl acetate extract were examined. Furthermore, possible molecular mechanisms of the anti-inflammatory effects were dissected. The anti-inflammatory activity was investigated by inhibition of lipopolysaccharide (LPS) induced pro-inflammatory cytokine production in murine macrophage-like cell line Raw264.7 cells and human microglial cell line BV2 cells. The measurement of the induced pro-inflammatory cytokine levels were carried out by ELISA. The phosphorylation of ERK1/2, JNK, and MAPK, and the nuclear expression of nuclear factor $NF-{\kappa}B$ p65 were investigated by Western blot analysis. The extract of ADS significantly decreased the production of pro-inflammatory cytokines. In addition, the extract suppressed the phosphorylation of ERK1/2, JNK, and p38 MAPK, and the nuclear translocation of $NF-{\kappa}B$ p65 in activated cells. Our findings provide evidence for the popular use of Abeliophylli distichum in inflammation around Goesan region and also suggest that the stem extract has potential therapeutic benefits against several inflammatory diseases.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2018.04a
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• pp.90-90
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• 2018

Kochiae Fructus is a medicinal plant used as medicine of the urinary organs, skin disease and inflammation. In this study, anti-inflammatory activity of Kochiae Fructus extract and its possible mechanisms of action were examined. The anti-inflammatory activity was investigated by inhibition of lipopolysaccharide (LPS) induced nitric oxide (NO), pro-inflammatory cytokine production and matrix metalloprotease-9 (MMP-9) in murine macrophage-like cell line Raw 264.7 cells. The measurement of the induced pro-inflammatory cytokine levels were carried out by ELISA. The phosphorylation of ERK1/2, JNK and MAPK and the nuclear expression of nuclear factor $NF-{\kappa}B$ p65 were investigated by Wesern blot analysis. The extract suppressed the phosphorylation of ERK1/2, JNK, and p38 MAPK, and the nuclear translocation of $NF-{\kappa}B$ p65 in activated cells. As a result, we suggest that the extract of Kochiae Fructus decreased the production of pro-inflammatory cytokines ($TNF-{\alpha}$, IL-6), nitric oxide, MMP-9 in LPS-induced Raw264.7 cells. Kochiae Fructus has possibility to be used as therapeutic benefits against inflammatory diseases.

• Journal of Ginseng Research
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• v.45 no.5
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• pp.575-582
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• 2021

Background: In ginseng, there exists a glycolipoprotein complex with a special form of lipid LPAs called Gintonin. The purpose of this study is to show that Gintonin has a therapeutic effect on rheumatoid arthritis through LPA2 receptors. Methods: Fibroblast-like synoviocytes (FLS) were treated with Gintonin and stimulated with interleukin (IL)-1β. The antioxidant effect of Gintonin was measured using MitoSOX and H₂DCFDA experiments. The anti-arthritic efficacy of Gintonin was examined by analyzing the expression levels of inflammatory mediators, phosphorylation of mitogen-activated protein kinase (MAPK) pathways, and translocation of nuclear factor kappa B (NF-κB)/p65 into the nucleus through western blot. Next, after treatment with LPAR2 antagonist, western blot analysis was performed to measure inflammatory mediator expression levels, and NF-κB signaling pathway. Carrageenan/kaolin-induced arthritis rat model was used. Rats were orally administered with Gintonin (25, 50, and 100 mg/kg) every day for 6 days. The knee joint thickness, squeaking score, and weight distribution ratio (WDR) were measured as the behavioral parameters. After sacrifice, H&E staining was performed for histological analysis. Results: Gintonin significantly inhibited the expression of iNOS, TNF-α, IL-6 and COX-2. Gintonin prevented NF-κB/p65 from moving into the nucleus through the JNK and ERK MAPK phosphorylation in FLS cells. However, pretreatment with an LPA2 antagonist significantly reversed these effects of Gintonin. In the arthritis rat model, Gintonin suppressed all parameters that were measured. Conclusion: This study suggests that LPA2 receptor plays a key role in mediating the anti-arthritic effects of Gintonin by modulating inflammatory mediators, the MAPK and NF-κB signaling pathways.

• The Korea Journal of Herbology
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• v.27 no.3
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• pp.31-38
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• 2012

Objectives : Mori Folium is one of the traditional medicinal herb. It was commonly used for sericulture in the world and has been traditionally administered as natural therapeutic agent for the treatment of filariasis, diabetes and dropsy in East Asia. This study investigated an anti-inflammatory potential of Mori Folium ethanol extract (MFE). Methods : We examined the effects of MFE on the lipopolysaccharide (LPS)-induced production of nitric oxide (NO) and prostaglandin $E_2$ ($PGE_2$) in a murine macrophage cell line, RAW 264.7. Results : MFE inhibited production of NO and $PGE_2$ in a dose dependent manner and also decreased the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2, interleukin (IL)-1, IL-6 and tumor necrosis factor-${\alpha}$. As a plausible molecular mechanism, increased degradation of I-${\kappa}B{\alpha}$ and phosphorylation of I-${\kappa}B{\alpha}$, NF-${\kappa}B$ and MAP kinases by LPS were partly blocked by MFE treatment. Conclusions : These results suggest that MFE has an anti-inflammatory therapeutic potential, which may result from inhibition of NF-${\kappa}B$ activation and MAPK phosphorylation, thereby decreasing the expression of pro-inflammatory genes.