• Biomolecules & Therapeutics
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• 제24권2호
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• pp.184-190
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• 2016

Rosa rugosa Thunb, a deciduous shrub of the genus Rosa, has been widely used to treat stomach aches, diarrhoea, pain, and chronic inflammatory disease in eastern Asia. In recent years, our research team has extensively studied the Rosa rugosa flower extract, and specifically undertook pharmacological experiments which have optimized the extraction process. Our methods have yielded a standard extract enriched in phenolic compounds, named PRE. Herein, we expand our efforts and evaluated the anti-inflammatory activity of PRE on lipopolysaccharide (LPS)-induced inflammation in RAW 264.7 macrophages. PRE significantly inhibited production of nitric oxide (NO), prostaglandin $E_2(PGE_2)$, tumor necrosis factor (TNF)-${\alpha}$, interleukin (IL)-6, and interleukin $1{\beta}$ (IL-$1{\beta}$), as well as expression of their synthesizing enzymes, inducible nitric oxide synthase (iNOS) and cyclooxygenase2 (COX-2). Furthermore, PRE inhibited activity of mitogen-activated protein kinases (MAPK) as well as nuclear factor-kappa B (NF-${\kappa}B$) signaling pathway. Our findings are the first to explain the anti-inflammatory mechanism by PRE in LPS-stimulated macrophages. Given these results, we propose that PRE has therapeutic potential in the prevention of inflammatory disorders.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 2000년도 춘계학술대회
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• pp.10-14
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• 2000

The cycloooxygenase enzymes catalyze the oxidative conversion of arachidonic acid into prostag1andin H$_2$Which mediates both benificial and pathological effects. The COX-1 is constitutively expressed in most tissues and in blood platelets wherease the expression of COX-2 isoform is induced in response to inflmmatory stimuli such as cyctokynes. Thus the identification of a novel COX-2 selective inhibitor should offer excellent antiinflammatory activity with minimal side effects such as gastrointestinal toxicity. Recently, a group of structurally unique and biologically active pimarane diterpenoids has been isolated from indigenous Korean medicinal plants. These new diterpenoids turned out to be potential analgesic and antiinflammatory agent due to their potent inhibitory activities of prostaglandin synthesis. We have also found that the inhibition of PGE$_2$synthesis is attributed to the potent COX inhibition by pimarane diterpenoid in arachidonic acid cascade. In conjunction with development of new analgesic and nonsteroidal antiinflammatory agent, a series of works on these diterpenoids have been extensively carried out in our laboratories. These efforts involve the structure-activity relationship of pimaradienoic acid, molecular modelings and COX inibitory activities as well as actiinflammatory effects of its structural analogues. In addition, the total syntheses of the new natural pimarane diterpenoids, their stereoisomers and other structural variants were intensively investigated.

• Asian Pacific Journal of Cancer Prevention
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• 제15권7호
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• pp.3219-3226
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• 2014

Chemotherapy continues to be a mainstay of cancer treatment, although drug resistance is a major obstacle. Lipid metabolism plays a critical role in cancer pathology, with elevated ether lipid levels. Recently, alkylglyceronephosphate synthase (AGPS), an enzyme that catalyzes the critical step in ether lipid synthesis, was shown to be up-regulated in multiple types of cancer cells and primary tumors. Here, we demonstrated that silencing of AGPS in chemotherapy resistance glioma U87MG/DDP and hepatic carcinoma HepG2/ADM cell lines resulted in reduced cell proliferation, increased drug sensitivity, cell cycle arrest and cell apoptosis through reducing the intracellular concentration of lysophosphatidic acid (LPA), lysophosphatidic acid-ether (LPAe) and prostaglandin E2 (PGE2), resulting in reduction of LPA receptor and EP receptors mediated PI3K/AKT signaling pathways and the expression of several multi-drug resistance genes, like MDR1, MRP1 and ABCG2. ${\beta}$-catenin, caspase-3/8, Bcl-2 and survivin were also found to be involved. In summary, our studies indicate that AGPS plays a role in cancer chemotherapy resistance by mediating signaling lipid metabolism in cancer cells.

• Biomolecules & Therapeutics
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• 제22권1호
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• pp.10-16
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• 2014

Derivatives of caffeic acid have been reported to possess diverse pharmacological properties such as anti-inflammatory, anti-tumor, and neuroprotective effects. However, the biological activity of methyl p-hydroxycinnamate, an ester derivative of caffeic acid, has not been clearly demonstrated. This study aimed to elucidate the anti-inflammatory mechanism of methyl p-hydroxycinnamate in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells. Methyl p-hydroxycinnamate significantly inhibited LPS-induced excessive production of pro-inflammatory mediators such as nitric oxide (NO) and $PGE_2$ and the protein expression of iNOS and COX-2. Methyl p-hydroxycinnamate also suppressed LPS-induced overproduction of pro-inflammatory cytokines such as IL-$1{\beta}$ and TNF-${\alpha}$. In addition, methyl p-hydroxycinnamate significantly suppressed LPS-induced degradation of $I{\kappa}B$, which retains NF-${\kappa}B$ in the cytoplasm, consequently inhibiting the transcription of pro-inflammatory genes by NF-${\kappa}B$ in the nucleus. Methyl p-hydroxycinnamate exhibited significantly increased Akt phosphorylation in a concentration-dependent manner. Furthermore, inhibition of Akt signaling pathway with wortmaninn abolished methyl p-hydroxycinnamate-induced Akt phosphorylation. Taken together, the present study clearly demonstrates that methyl p-hydroxycinnamate exhibits anti-inflammatory activity through the activation of Akt signaling pathway in LPS-stimulated RAW264.7 macrophage cells.

• 생약학회지
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• 제43권3호
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• pp.217-223
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• 2012

In the present study, we investigated anti-inflammatory activity of artemisinic acid in HaCaT cells and RAW264.7 cells. Artemisinic acid showed inhibitory activity on macrophage-derived chemokines (MDC) expression, a factor related with atopic dermatitis (AD), in interferon (IFN)-${\gamma}$ and tumor necrosis factor (TNF)-${\alpha}$-stimulated HaCaT cells. In the study on action mechanism, pretreated artemisinic acid reduced the phosphorylation of STAT1 and p38 and the degradation of $I{\kappa}B$ by IFN-${\gamma}$ and TNF-${\alpha}$ stimulations. However, artemisinic acid didn't show the inhibitory activity on LPS-induced inflammatory mediators (NO, $PGE_2$, IL-6) in RAW264.7 cell. These results indicate that artemisinic acid inhibits IFN-${\gamma}$ and TNF-${\alpha}$-induced MDC expression through inhibition of signal factors, STAT1, NF-${\kappa}B$, and p38, in HaCaT keratinocytes.

• Natural Product Sciences
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• 제16권3호
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• pp.153-158
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• 2010

To fine out the anti-inflammatory activities of the C. fragile. and its mechanism were investigated in macrophages induced by Peptidoglycan (PGN). Treatments of macrophages with 100 ug/ml of ethanol extract of Codium fragile (EECF) inhibited PGN-induced IL-6, NO and PGE2 production in a dose-dependent manner as well as expression of iNOS and COX-2. EECF inhibited PGN-induced extracellular signal-regulated kinase (ERK) 1/2, JNK 1/2 and p38 MAPK phosphorylation, which suggests that EECF inhibits IL-6 and NO secretion by blocking MAPKs phosphorylation. These findings may help elucidate the mechanism by which EECF modulates RAW 264.7 cell activation under inflammatory conditions.

• 한국약용작물학회지
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• 제26권3호
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• pp.233-239
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• 2018

Background: Inflammation plays an important role in various diseases, including ulcerative colitis, Behcet's disease, and rheumatoid arthritis. In this study, we investigated the anti-inflammatory effects of Morus alba L. extracts obtained using different extraction methods (water extraction or high temperature extraction) on RAW264.7 cells. Methods and Results: Extracts from the central part (including the heartwood, sapwood, cambiun, and phloem) and bark (including the periderm and cortex) of Morus alba L. were obtained using either water or high temperature extraction. The following extract were obtained: MA1, water extract from the central part of Morus alba L., MA2, high temperature extract from the central part of Morus alba L., MA3, water extract from the bark of Morus alba L., and MA4, high temperature extract from the bark of Morus alba L. None of these extracts was observed to be cytotoxic to RAW264.7 cells. The MA2 extract reduced the production of LPS-induced NO (nitric oxide), $PGE_2$ (prostaglandin $E_2$), $TNF-{\alpha}$, IL-6, and $IL-1{\beta}$ production in LPS-stimulated RAW264.7 cells. Conclusions: These results indicated that the inflammatory response was moderated by MA2. Treatment with MA2 could be used as a natural medicine for treating diseases involving inflammation. However, further experiments are required to determine how the high temperature extraction method alters the active ingredients in the extract and influences the anti-inflammatory effects of Morus alba L..

• 사상체질의학회지
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• 제22권4호
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• pp.56-64
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• 2010

1. Objectives 4 herbal formulas (Yanggyeoksanhwa-tang, Yeoldahanso-tang, Cheongsimyeonja-tang and Taeeumjowi-tang) were applied to investigate the anti-inflammatory activities. In many studies, plant-derived anti-inflammatory efficacies have been investigate for their potential inhibitory effects on lipopolysaccharide (LPS)-stimulated macrophages. This study was performed to examine the anti-inflammatory activities of 4 herbal formulas on LPS-stimulated RAW 264.7 cells. 2. Methods The productions of nitric oxide (NO), prostaglandin (PG)$E_2$, interleukin(IL)-6 and tumor necrosis factor (TNF)-${\alpha}$ were examined in the presence of the 4 herbal formulas in RAW 264.7 cells. The cells were incubated with LPS 1 ${\mu}g/mL$ and 4 herbal formulas for 18 hrs. The anti-inflammatory activity of 4 herbal formulas were investigate by carrageenin-induced paw edema in rats. The paw volume was measured at 2 and 4 hrs following carrageenininduced paw edema in rats. 3. Results Yanggyeoksanhwa-tang and Cheongsimyeonja-tang showed inhibitory effect on $PGE_2$ production in LPS-stimulated RAW 264.7 cells and a reduction in carrageenin-induced paw edema on rats. Yanggyeoksanhwa-tang showed inhibitory effect on IL-6 in LPS-stimulated RAW 264.7 cells. 4 herbal formulas not affect on NO and TNF-${\alpha}$ inhibition in LPS-stimulated RAW 264.7 cells. 4. Conclusions These results suggested that Yanggyeoksanhwa-tang and Cheongsimyeonja-tang have anti-inflammatory activity.

• 대한한의학회지
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• 제31권3호
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• pp.47-54
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• 2010

Objective: To derive information on the efficacy of Sam-chul-kun-bi-tang (SKT), by evaluating its anti-inflammatory effect. SKT is a widely-used herbal formula in traditional Korean medicine. In man y studies, plant-derived anti-inflammatory efficacies have been investigated for their potential inhibitory effects on lipopolysaccharide (LPS)-stimulated macrophages. This study was performed to examine the anti-inflammatory effects of SKT extract on LPS-stimulated RAW 264.7 cells. Methods: The production of nitric oxide (NO), prostaglandin $(PG)E_2$, tumor necrosis factor (TNF)-$\alpha$ and interleukin (IL)-6 were examined in a macrophage cell line, RAW 264.7 cells, in the presence of SKT. RAW 264.7 cells were incubated with LPS 1 ${\mu}g/mL$ and SKT for 18 hrs. The anti-inflammatory activity of SKT was investigated by carrageenan-induced paw edema in rats. The paw volume was measured at 2 and 4 hrs following carrageenan-induced paw edema in rats. Results: SKT showed inhibitory effect on $PGE_2$, TNF-$\alpha$ and IL-6 in LPS-stimulated RAW 264.7 cells. But SKT was not inhibitory effect on NO by LPS-stimulated RAW 264.7 cells. Administration of SKT (1 g/kg) also showed a reduction in carrageenan-induced paw edema on rats. Conclusion: These results suggest that SKT has anti-inflammatory activities in both in vitro and in vivo models.

• 한방안이비인후피부과학회지
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• 제30권1호
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• pp.74-86
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• 2017

Objectives : This study aimed to assess the scientific evidence for the use of Hwanglyeonhaedok-tang, a traditional herbal formula, in the treatment of rhinitis, and prepare the basis for the investigational new drug application by analyzing the experimental studies. Methods : Ten electronic databases were searched up to December, 2016 without language limitation. Experimental studies on the anti-inflammatory and anti-allergic effects of Hwanglyeonhaedok-tang against rhinitis were included. We extracted data about study design, characteristics of intervention, outcomes, and pharmacological effects from the included studies and summarized them. Results : Eight hundred and thirty-three potentially relevant studies were identified, of which 18 experimental studies met our inclusion criteria. Of 18 included studies, 5 had conducted cell viability test, and all studies had reported that Hwanglyeonhaedok-tang was non-cytotoxic. Hwanglyeonhaedok-tang exhibits anti-inflammatory effect by regulating the inflammation-related cytokines including nitric oxide(NO), prostaglandin $E_2(PGE_2)$, interleukin-6(IL-6), and tumor necrosis $factor-{\alpha}(TNF-{\alpha})$ in vitro and in vivo. Hwanglyeonhaedok-tang exhibits anti-allergic effect by suppressing eosinophil, and histamine levels. Hwanglyeonhaedok-tang helps in the recovery of nasal mucous membrane by supressing goblet cells, heat shock protein 70, and substance P. Conclusions : This study suggests that Hwanglyeonhaedok-tang has the potential to be developed as therapeutic agent for rhinitis. Further experimental and clinical studies needed to be performed to prove the safety and efficacy.