• Journal of Acupuncture Research
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• v.39 no.1
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• pp.40-48
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• 2022

Background: This study was performed to determine the effects of liposome-encapsulated bee venom (BV) treatment of inflammatory factors in atopic dermatitis (AD) compared with BV treatment. Methods: AD was induced by phthalic anhydride in mice and the effects of BV liposomes were measured. Using Leica Application Suite, thickened epidermis and dermis were measured after BV liposome treatment (0.05 and 0.1 ㎍/mL). The number of stained mast cells and the concentration of immunoglobulin (Ig)E were measured. Serum IgE concentration was analyzed using an enzyme-linked immunosorbent assay. The serum concentrations of interleukin (IL)-1, IL-4, and IL-6 inflammatory cytokines were measured. The levels of messenger ribonucleic acid expression of proinflammatory cytokines and chemokines were measured using reverse transcription polymerase chain reaction. Inhibition of mitogen-activated protein kinase activation, was analyzed on western blot. To measure the transcriptional activity (NF-κB inhibition by BV liposomes), western blots (p65, p-IκB, p50, and IκB) were also performed. Results: The weight of lymph nodes, serum IgE concentrations, morphological changes in the skins from the backs of the mice, and mast cell numbers in inflamed tissues were noticeably lower in the BV liposome treatment group compared with the BV treatment group. The concentrations of pro-inflammatory cytokines (IL-1, IL-4, IL-6) and chemokines (TSLP, CCL22) were also reduced. Activation of mitogen-activated protein kinase (p-ERK and p-p38), and transcriptional activity (p65, p-IκB, p50, and IκB) was strongly suppressed in the BV liposome group. Conclusion: BV liposomes may have a better therapeutic effect than BV for the treatment of AD.

• Natural Product Sciences
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• v.21 no.4
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• pp.240-247
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• 2015

Viridicatol (1) has previously been isolated from the extract of the marine-derived fungus Penicillium sp. SF-5295. In the course of further biological evaluation of this quinolone alkaloid, anti-inflammatory effect of 1 in RAW264.7 and BV2 cells stimulated with lipopolysaccharide (LPS) was observed. In this study, our data indicated that 1 suppressed the expression of well-known pro-inflammatory mediators such as inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2, and consequently inhibited the production of iNOS-derived nitric oxide (NO) and COX-2-derived prostaglandin E2 ($PGE_2$) in LPS stimulated RAW264.7 and BV2 cells. Compound 1 also reduced mRNA expression of pro-inflammatory cytokines such as $interleukin-1{\beta}$ ($IL-1{\beta}$), interleukin-6 (IL-6), and tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$). In the further evaluation of the mechanisms of these anti-inflammatory effects, 1 was shown to inhibit nuclear factor-kappa B ($NF-{\kappa}B$) pathway in LPS-stimulated RAW264.7 and BV2 cells. Compound 1 blocked the phosphorylation and degradation of inhibitor kappa B $(I{\kappa}B)-{\alpha}$ in the cytoplasm, and suppressed the translocation of $NF-{\kappa}B$ p65 and p50 heterodimer in nucleus. In addition, viridicatol (1) attenuated the DNA-binding activity of $NF-{\kappa}B$ in LPS-stimulated RAW264.7 and BV2 cells.

• Journal of Acupuncture Research
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• v.21 no.3
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• pp.121-131
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• 2004

Objective : The purpose of this study was investigation how the bee venom(BV) prevents inflammation in human cell. Methods : we induced inflammation on human synoviocyte cell by lipopolysaccharide(LPS) and sodium nitroprusside(SNP), treated the bee venom and melittin on this cell, surveyed the expression of Nisotric oxide(NO), inducible nitric oxide synthase(iNOS), Cyclooxygenease-2(COX-2), cytolic phospholipase $A_2(cPLA_2)$, Prostaglandin $E_2(PGE_2)$ and nuclear factor-${\kappa}B$(NF-${\kappa}B$), and got below conclusions. Results : Compared with control 1. Expressions of LPS-induced $PGE_2$(BV 1, $5{\mu}g/m{\ell}$) and SNP-induced PGE2(BV 0.5, 1, $5{\mu}g/m{\ell}$)were decreased significantly. 2. Expressions of LPS-induced NO(BV 0.5, 1, $5{\mu}g/m{\ell}$) and SNP-induced NO(BV 1, $5{\mu}g/m{\ell}$)were decreased significantly. 3. Expressions of LPS-induced COX-2(BV 1, $5{\mu}g/m{\ell}$) and SNP-induced COX-2(BV $5{\mu}g/m{\ell}$)were decreased significantly. 4. Expressions of LPS-induced iNOS(BV 0.5, 1, $5{\mu}g/m{\ell}$) and SNP-induced iNOS(BV $5{\mu}g/m{\ell}$) were meanless by all dose. 5. Expressions of LPS-induced $cPLA_2$(BV 1, $5{\mu}g/m{\ell}$) and SNP-induced cPLA2(BV 1, $5{\mu}g/m{\ell}$)were decreased significantly. 6. Expressions of LPS-induced NF-${\kappa}B$(BV $5{\mu}g/m{\ell}$, melittin $5{\mu}g/m{\ell}$) and SNP-induced NF-${\kappa}B$(BV 0.5, 1, $5{\mu}g/m{\ell}$, melittin 5, $10{\mu}g/m{\ell}$)were decreased significantly. 7. Expressions of LPS-induced NF-${\kappa}B$ binding activity (BV $1{\mu}g/m{\ell}$, melittin $5{\mu}g/m{\ell}$, melittin $5{\mu}g/m{\ell}$+ DTT 20mM) were decreased significantly. Conclusion : The bee venom treatments on synoviocyte showed significant changes in LPS and SNP induced NO, iNOS, COX-2, cPLA2, PGE2 and NF-${\kappa}B$, these results suggest that bee venom is effective to inflammations and establish the process of bee venom therapy, so we expect active use of bee venom to control the inflammation.

• Journal of Marine Bioscience and Biotechnology
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• v.12 no.1
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• pp.29-39
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• 2020

In this study, we investigated the inhibitory potential of an ethanol extract of Carpomitra costata (EECC) (Stackhouse) Batters, a brown alga, against neuroinflammatory responses in lipopolysaccharide (LPS)-stimulated BV2 microglia. Our results showed that EECC significantly suppressed the LPS-induced secretion of pro-inflammatory mediators, including nitric oxide (NO) and prostaglandin E₂, with no significant cytotoxic effects. EECC also inhibited the LPS-induced expression of their regulatory enzymes, such as inducible NO synthase and cyclooxygenase-2. In addition, EECC downregulated the LPS-induced expression and production of the proinflammatory cytokines, tumor necrosis factor-α and interleukin-1β. In the mechanistic assessment of the antineuroinflammatory effects, EECC was found to inhibit the nuclear translocation and DNA binding of nuclear factor-kappa B (NF-κB) by disrupting the degradation of the κB-α inhibitor in the cytoplasm. Moreover, EECC effectively suppressed the enhanced expression of Toll-like receptor 4 (TLR4) and myeloid differentiation factor 88, as well as the binding of LPS to TLR4 in LPS-treated BV2 cells. Furthermore, EECC markedly reduced the LPS-induced generation of reactive oxygen species (ROS), demonstrating a strong antioxidative effect. Collectively, these results suggest that EECC repressed LPS-mediated inflammatory action in the BV2 microglia through the inactivation of NF-κB signaling by antagonizing TLR4 and/or preventing ROS accumulation. While further studies are needed to fully understand the anti-inflammatory effects associated with the antioxidant activity of EECC, the current findings suggest that EECC has a potential advantage in inhibiting the onset and treatment of neuroinflammatory diseases.

• Biomolecules & Therapeutics
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• v.26 no.2
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• pp.210-217
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• 2018

Neuroinflammation is an immune response within the central nervous system against various proinflammatory stimuli. Abnormal activation of this response contributes to neurodegenerative diseases such as Parkinson disease, Alzheimer's disease, and Huntington disease. Therefore, pharmacologic modulation of abnormal neuroinflammation is thought to be a promising approach to amelioration of neurodegenerative diseases. In this study, we evaluated the synthetic flavone derivative 3',4'-dihydroxyflavone, investigating its anti-neuroinflammatory activity in BV2 microglial cells and in a mouse model. In BV2 microglial cells, 3',4'-dihydroxyflavone successfully inhibited production of chemokines such as nitric oxide and prostaglandin $E_2$ and proinflammatory cytokines such as tumor necrosis factor alpha, interleukin 1 beta, and interleukin 6 in BV2 microglia. It also inhibited phosphorylation of mitogen-activated protein kinase (MAPK) and nuclear factor $(NF)-{\kappa}B$ activation. This indicates that the anti-inflammatory activities of 3',4'-dihydroxyflavone might be related to suppression of the proinflammatory MAPK and $NF-{\kappa}B$ signaling pathways. Similar anti-neuroinflammatory activities of the compound were observed in the mouse model. These findings suggest that 3',4'-dihydroxyflavone is a potential drug candidate for the treatment of microglia-related neuroinflammatory diseases.

• Journal of Acupuncture Research
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• v.23 no.3
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• pp.117-127
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• 2006

Alzheimer's disease (AD) is the most prevalent form of neurodegenerative disease associated with aging in the human population. This disease is characterized by the following 4 structural changes : Atrophy of the Cortex, Parasympathetic, and other neural cells, the existence of Neurofibrillary tangles (NFTs), and the accumulation of Senile plaques. NFTs and Senile plaques is known to be the index of this disease. Senile plaques disturbs the neutro transmission and depletes of Acetylcholine. So, Recovery of Acetylcholine is the primal objective for treating Alzheimer's disease. So, Inhibiting the activity of Acetylcholine Esterase (AChE), which causes the hydrolysus of acetylcholine into choline and acetate, can be seen as a key role for treating Alzheimer's disease. Increasing body of evidence has been demonstrated that Bee Venom Acupuncture (BV) could compete with complex protein involving in multiple step of $NF-_{\kappa}B$ activation and exert the anti-inflammatory potential of combined inhibition of the prostanoid and nitric oxide synthesis systems by inhibition of IKK and $NF-_{\kappa}B$. BV dose-dependently attenuated Scopolamine-induced Acetylcholine esterase activities in cerebral cortex and hippocampus of the mice brain. This study therefore suggests that BV acupuncture method may be useful for prevention of development or progression of AD.

• 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.

• Journal of Acupuncture Research
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• v.23 no.3
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• pp.103-115
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• 2006

Alzheimer's disease (AD) is the most prevalent form of neurodegenerative disease associated with aging in the human population. This disease is characterized by the following 4 structural changes : Atrophy of the Cortex, Parasympathetic, and other neural cells, the existence of Neurofibrillary tangles (NFTs), and the accumulation of Senile plaques. NFTs and Senile plaques is known to be the index of this disease. Senile plaques disturbs the neutro transmission and depletes of Acetylcholine. So, Recovery of Acetylcholine is the primal objective for treating Alzheimer's disease. So, Inhibiting the activity of Acetylcholine Esterase (AChE), which causes the hydrolysus of acetylcholine into choline and acetate, can be seen as a key role for treating Alzheimer's disease. Increasing body of evidence has been demonstrated that Bee Venom Acupuncture (BV) could compete with complex protein involving in multiple step of $NF-_{\kappa}B$ activation and exert the anti -inflammatory potential of combined inhibition of the prostanoid and nitric oxide synthesis systems by inhibition of IKK and $NF-_{\kappa}B$. The effect of BV through behavioral tests after memory impairment induced by Scopolamine. We examined the improving effect of BV on the Scopolamine (1 mg/Kg, i.p.)-induced memorial impairment using passive avoidance response and water maze tests in the mice. BV (0.84, $1.67\;{\mu}g/ml$) reversed the Scopolamine-induced memorial impairment in dose dependent manner. This study therefore suggests that BV acupuncture method may be useful for prevention of development or progression of AD.

• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.4
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• pp.921-933
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• 2007

This experiment was designed to investigate the effects of the KBCMT hot water extract & ultra-fine powder on Alzheimer's Disease Model Induced by ${\beta}A$. The effects of the KBCMT hot water extract on expression of $IL-1{\beta}$, IL-6, $TNF-{\alpha}$, NOS-II, COX-2 mRNA and production of $IL-1{\beta}$, IL-6, $TNF-{\alpha}$, NO in BV2 microglial cell line treated by lipopolysacchaide(LPS). The effects of the KBCMT hot water extract & ultra-fine powder on (1) the behavior (2) expression of $IL-1{\beta}$, $TNF-{\alpha}$, MDA, CD68 and CD11b; (3) AChE in serum (4) the infarction area of the hippocampus, and brain tissue injury in Alzheimer's diseased mice induced with ${\beta}A$ were investigated. The KBCMT hot water extract suppressed the expression of $IL-1{\beta}$, IL-6 and $TNF-{\alpha}$ mRNA in BV2 microglia cell line treated with LPS. The KBCMT hot water extract suppressed the production of $IL-1{\beta}$, IL-6, $TNF-{\alpha}$, NO in BV2 microglial cell line treated with LPS. The KBCMT hot water extract & ultra-fine powder a significant inhibitory effect on the memory deficit was shown for the mice with Alzheimer's disease induced by ${\beta}A$ in the Morris water maze experiment, which measured stop-through latency and distance movemet-through latency The KBCMT ultra-fine powder suppressed the expression of TNF-a protein significantly in the microglial cell of mice with Alzheimer's disease induced by ${\beta}A$. The KBCMT hot water extract & ultra-fine powder reduced the MDA and suppressed the over-expression of CD68, CD11b in the mice with Alzheimer's disease induced by ${\beta}A$. The KBCMT hot water extract & ultra-fine powder decreased AChE significantly in the serum of the mice with Alzheimer's disease induced by ${\beta}A$. The KBCMT hot water extract & ultra-fine powder reduced infarction area of hippocampus, and controlled the injury of brain tissue in the mice with Alzheimer's disease induced by ${\beta}A$. The KBCMT hot water extract & ultra-fine powder reduced the tau protein, GFAP, and presenilin1, 2 of hippocampus in the mice with Alzheimer's disease induced by ${\beta}A$. These results suggest that the KBCMT hot water extract & ultra-fine powder may be effective for the prevention and treatment of Alzheimer's disease. Investigation into the clinical use of the KBCMT hot water extract & ultra-fine powder for Alzheimer's disease is suggested for future research.

• Korean Journal of Pharmacognosy
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• v.51 no.4
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• pp.244-254
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• 2020

Atractylodes macrocephala is a perennial herb and is a member of the Compositae family. This plant is known to contain various bioactive constituents indicating anti-inflammatory, neuroprotective, anti-oxidant, immunological enhancement, and gastroprotective effects. In this investigation, we isolated four compounds with similar chemical structures from A. macrocephala, and evaluated their anti-inflammatory effects. Among the four compounds, compound 2(atractylenolide II) showed the second-best inhibitory effect on the lipopolysaccharide(LPS)-induced production of nitric oxide in RAW264.7 macrophages and BV2 microglial cells. Compound 2 also inhibited the LPS-induced the production of prostaglandin E2(PGE2), and the expression of inducible nitric oxide synthase(iNOS) and cyclooxygenase(COX)-2 proteins in both cells. In addition, compound 2 suppressed the production of pro-inflammatory cytokines including interleukin(IL)-1β, 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 treatment with compound 2. This compound did not induce the expression of heme oxygenase(HO)-1 protein indicating that the anti-inflammatory effect of compound 2 was independent with HO-1 protein. Taken together, these results suggested that atractylenolide II can be a candidate material to treat inflammatory diseases.