• Korean Journal of Pharmacognosy
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• v.50 no.4
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• pp.291-298
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• 2019

Phlox subulata is a perennial herbaceous flower and is a member of the Polemoniaceae family. This plant is known to resist to various stresses including salt, drought, heat, and cold stresses. In this investigation, we evaluated the ant-inflammatory effect of the methanolic extract of P.subulata(PSM) on lipopolysaccharide(LPS)-induced RAW264.7 macrophages and BV2 microglia. PSM reduced the production of nitric oxide(NO) in LPS-stimulated both RAW264.7 and BV2 cells, but did not affect to the production of prostaglandin E2(PGE₂). It inhibited the expression of inducible nitric oxide synthase(iNOS) and cyclooxygenase(COX)-2 in both cells. In addition, PSM suppressed the production of pro-inflammatory cytokines including interleukin(IL)-6 and tumor necrosis factor(TNF)-α. These inhibitory effects were contributed by inactivation of nuclear factor kappa B(NF-κB) and mitogen-activated protein kinases(MAPKs) pathways by PSM. Thus, these results suggested that P.subulata can be a candidate material to treat inflammatory diseases.

• 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.

• Biomolecules & Therapeutics
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• v.17 no.3
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• pp.263-269
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• 2009

4-Hydroxybenzaldehyde, a phenolic compound found in a variety of natural sources, was previously shown to contain anti-inflammatory and related anti-angiogenic and anti-nociceptive activities. The present work was designed to assess some pharmacological activities of 2,4-dihydroxybenzaldehyde (DHD), an analogue of 4-hydroxybenzaldehyde. DHD exhibited a significant inhibition in the chick chorioallantoic membrane (CAM) angiogenesis, and its $IC_{50}$ value was $2.4\;{\mu}g/egg$. DHD also contained in vivo anti-inflammatory activity using acetic acid-induced permeability and carrageenan-induced air pouch models in mice. In the air pouch model, DHD showed significant suppression in exudate volume, number of polymorphonuclear leukocytes and nitrite content. DHD showed an anti-nociceptive activity in the acetic acid-induced writhing test in mice. It also suppressed enhanced production of nitric oxide (NO) and elevated expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells. It was able to slightly decrease the level of reactive oxygen species in the stimulated macrophages. DHD at the used concentrations couldn't modulate the viabilities of RAW264.7 cells. Taken together, like 4-hydroxybenzaldehyde, DHD contains anti-angiogenic, anti-inflammatory and anti-nociceptive activities.

• Nutrition Research and Practice
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• v.8 no.5
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• pp.487-493
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• 2014

BACKGROUND/OBJECTIVES: D. candidum is a traditional Chinese food or medicine widely used in Asia. There has been little research into the anticancer effects of D. candidum, particularly the effects in colon cancer cells. The aim of this study was to investigate the anticancer effects of D. candidum in vitro and in vivo. MATERIALS/METHODS: The in vitro anti-cancer effects on HCT-116 colon cancer cells and in vivo anti-metastatic effects of DCME (Dendrobium canidum methanolic extract) were examined using the experimental methods of MTT assay, DAPI staining, flow cytometry analysis, RT-PCR, and Western blot analysis. RESULTS: At a concentration of 1.0 mg/mL, DCME inhibited the growth of HCT-116 cells by 84%, which was higher than at concentrations of 0.5 and 0.25 mg/mL. Chromatin condensation and formation of apoptotic bodies were observed in cancer cells cultured with DCME as well. In addition, DCME induced significant apoptosis in cancer cells by upregulation of Bax, caspase 9, and caspase 3, and downregulation of Bcl-2. Expression of genes commonly associated with inflammation, NF-${\kappa}B$, iNOS, and COX-2, was significantly downregulated by DCME. DCME also exerted an anti-metastasis effect on cancer cells as demonstrated by decreased expression of MMP genes and increased expression of TIMPs, which was confirmed by the inhibition of induced tumor metastasis in colon 26-M3.1 cells in BALB/c mice. CONCLUSIONS: Our results demonstrated that D. candidum had a potent in vitro anti-cancer effect, induced apoptosis, exhibited anti-inflammatory activities, and exerted in vivo anti-metastatic effects.

• Herbal Formula Science
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• v.25 no.4
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• pp.471-481
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• 2017

Objectives : Noemyeong-san (NMS) is a novel herbal prescription composed of five oriental medicinal herbs including Prunellae Spica, Betulae Cortex, Foeniculi Fructus, Asiasari Radix, and Clematidis Radix for treating Alzheimer's disease. In the present study, we investigated the effects and molecular mechanisms of NMS on BV2 microglia to evaluate the potential action of this formula for preventing or treating neurodegenerative disease such as Alzheimer's disease. Methods : To determine the cytotoxicity of NMS on BV2 microglia, the MTT assay was performed. The effects of NMS on lipopolysaccharide (LPS)-stimulated BV2 microglia were determined with a nitric oxide (NO) assay and western blots for inflammatory mediator-related proteins, mitogen activated protein kinases (MAPKs), nuclear factor kappa B (NF-${\kappa}B$) pathway-related proteins, and heme oxygenase-1 (HO-1). Result : NMS inhibited induction of iNOS and COX-2 as well as NO production without affecting the cell viability in LPS-stimulated BV2 microglia. NMS also suppressed activation of ERK and p38 MAPK among main kinases of MAPKs as well as NF-${\kappa}B$ by LPS stimulation. Furthermore, NMS dose-dependently induced the expression of HO-1 and the inhibitory effect of NMS on the production of NO were blocked by pretreatment with an HO-1 inhibitor, Snpp. Conclusions : These results demonstrate that NMS has potent anti-neuroinflammatory effect on the LPS-stimulated microglia. These findings provide evidences for NMS to be considered as a new prescription for preventing or treating neurodegenerative disease such as Alzheimer's disease.

• BMB Reports
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• v.51 no.7
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• pp.362-367
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• 2018

A major feature of type 1 diabetes mellitus (T1DM) is hyperglycemia and dysfunction of pancreatic ${\beta}$-cells. In a previous study, we have shown that Tat-DJ-1 protein inhibits pancreatic RINm5F ${\beta}$-cell death caused by oxidative stress. In this study, we examined effects of Tat-DJ-1 protein on streptozotocin (STZ)-induced diabetic mice. Wild type (WT) Tat-DJ-1 protein transduced into pancreas where it markedly inhibited pancreatic ${\beta}$-cell destruction and regulated levels of serum parameters including insulin, alkaline phosphatase (ALP), and free fatty acid (FFA) secretion. In addition, transduced WT Tat-DJ-1 protein significantly inhibited the activation of $NF-{\kappa}B$ and MAPK (ERK and p38) expression as well as expression of COX-2 and iNOS in STZ exposed pancreas. In contrast, treatment with C106A mutant Tat-DJ-1 protein showed no protective effects. Collectively, our results indicate that WT Tat-DJ-1 protein can significantly ameliorate pancreatic tissues in STZ-induced diabetes in mice.

• Biomolecules & Therapeutics
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• v.19 no.3
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• pp.331-335
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• 2011

In this study, we determined the anti-inflammatory activity and mechanism of action of a hexane fraction (hWRF) obtained from white Rosa hybrida flowers by employing various assays such as quantitative real-time PCR, Western blotting, and Electrophoretic-Mobility Shift Assay (EMSA). The results revealed that the hWRF had excellent anti-inflammatory potency by reducing inflammatory repertoires, such as inducible nitric oxide synthase (iNOS), interleukin-$1{\beta}$, and cyclooxygenase-2 (COX-2) in RAW264.7 cells when stimulated with lipopolysaccharide (LPS), a pro-inflammatory mediator. The reduction of nitric oxide (NO) release from RAW 264.7 cells supported the anti-inflammatory effect of hWRF. Interestingly, hWRF effectively inhibited LPS-mediated nuclear factor-${\kappa}B$ (NF-${\kappa}B$) p65 subunit translocation into the nucleus and extracellular signal-regulated kinase (ERK)1/2 phosphorylation, suggesting that hWRF anti-inflammatory activity may be based on inhibition of the NF-${\kappa}B$ and MAPK pathways. Based on the findings described in this study, hWRF holds promise for use as a potential anti-inflammatory agent for either therapeutic or functional adjuvant purposes.

• Biomolecules & Therapeutics
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• v.21 no.5
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• pp.398-404
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• 2013

During a screening program to search the anticolitic herbal medicines, 80% ethanol extract of the rhizome of Anemarrhena asphodeloides (AA) was found to potently inhibit the expression of proinflammatory cytokines TNF-${\alpha}$ and IL-1${\beta}$, as well as the activation of NF-${\kappa}B$ in LPS-stimulated colonic macrophages, followed by that of the rhizome of C. chinensis (CC). AA also potently inhibited TNBS-induced colitic markers, shortening of the colon and increase of macroscopic score, myeloperoxidase activity, TNF-${\alpha}$, IL-1${\beta}$, and IL-6, in mice. The synergistic effect of CC against the anticolitic effect of AA was investigated. CC synergistically inhibited the anticolitic effect of AA. AC-mix (AA+CC, 1:1) potently inhibited them. AC-mix also inhibited the activation of NF-${\kappa}B$, as well as the expression of TNF-${\alpha}$, IL-1${\beta}$, IL-6, iNOS and COX-2. The effects of AC-mix against oxazolone-induced colitis were investigated in mice. AC-mix also potently inhibited oxazolone-induced inflammatory markers, colon shortening, macroscopic score, myeloperoxidase activity, NF-${\kappa}B$ activation and proinflammatory cytokines. Overall, the anti-colitic effect of AC-mix was superior to that of mesalazine. Based on these findings, AC-mix may improve colitis by inhibiting NF-${\kappa}B$ activation.

• Biomolecules & Therapeutics
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• v.25 no.5
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• pp.519-527
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• 2017

Excessive activation of microglia causes the continuous production of neurotoxic mediators, which further causes neuron degeneration. Therefore, inhibition of microglial activation is a possible target for the treatment of neurodegenerative disorders. Balanophonin, a natural neolignoid from Firmiana simplex, has been reported to have anti-inflammatory and anti-cancer effects. In this study, we aimed to evaluate the anti-neuroinflammatory effects and mechanism of balanophonin in lipopolysaccharide (LPS)-stimulated BV2 microglia cells. BV2 microglia cells were stimulated with LPS in the presence or absence of balanophonin. The results indicated that balanophonin reduced not only the LPS-mediated TLR4 activation but also the production of inflammatory mediators, such as nitric oxide (NO), prostaglandin E2 (PGE2), $Interleukin-1{\beta}$ ($IL-1{\beta}$), and tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$), in BV2 cells. Balanophonin also inhibited LPS-induced inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX2) protein expression and mitogen activated protein kinases (MAPKs), including extracellular signal-regulated kinase (ERK1/2), c-Jun N-terminal kinase (JNK), and p38 MAPK. Interestingly, it also inhibited neuronal cell death resulting from LPS-activated microglia by regulating cleaved caspase-3 and poly ADP ribose polymerase (PARP) cleavage in N2a cells. In conclusion, our data indicated that balanophonin may delay the progression of neuronal cell death by inhibiting microglial activation.

• Korean Journal of Pharmacognosy
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• v.45 no.1
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• pp.17-22
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• 2014

Grapes has long been used for food, and reported as containing polyphenol which has antioxidant and anti-cancer effects. Neuroinflammation is chronic inflammation at the brain, lead to neurodegenerative diseases. In this study, quercetin-3-O-glucuronide (QG) isolated from the leaf of Vitis labruscana has anti-neuroinflammatory effects. QG were investigated using MTT assay, western blot, nitric oxide (NO) assay, prostaglandin $E_2$ ($PGE_2$) assay, cytokine assay in lipopolysaccharide (LPS)-induced inflammation in BV2 cells. QG dose-dependently attenuated the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), accordingly inhibited the production of NO and $PGE_2$. QG decreases the levels of proinflammatory cytokine such as tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), interlukin-$1{\beta}$ (IL-$1{\beta}$). Thereby, QG may offer therapeutic potential for treatment of neurodegenerative disease related to neuroinflammation.