• 대한의생명과학회지
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• 제24권4호
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• pp.365-371
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• 2018

In this study, antioxidant and anti-neuroinflammatory of ethanol extracts from walnuts's (Juglans regia L.) shell were investigated in vitro. Radical-scavenging activities of the walnuts's shell ethanol extracts (WSE) were examined by using ABTS radicals and ${\alpha},{\alpha}$-diphenyl-${\beta}$-picrylhydrazyl (DPPH) radicals assay. In the ABTS and DPPH radical scavenging activity, $RC_{50}$ of WSE were measured as 15.74 and $40.13{\mu}g/mL$, respectively. Also, to evaluate the anti-neuroinflammatory effects of WSE in lipopolysaccharide (LPS)-stimulated BV-2 microglial cells. The production of proinflammatory cytokines NO were examined by LPS in BV-2 cell. BV-2 cells activated with LPS were treated with various doses (10, 25, 50, $100{\mu}g/mL$) of WSE. Supernatants were analyzed for the production of NO using Griess reagent. WSE up to $10{\mu}g/mL$ still required to inhibit NO induced by LPS. These results showed that walnuts's (Juglans regia L.) shell can be used as an easily accessible source of natural anti-neuroinflammatory and natural antioxidants.

• 대한본초학회지
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• 제37권5호
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• pp.83-88
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• 2022

Objectives : Jakyakgamcho-tang (JGT) has been traditionally used to treat muscular convulsion and pain in South Korea. According to recent studies, JGT has been reported to have anti-depression, anti-inflammation, anti-oxidative, anti-diabetics, anti-spasm and analgesic effects, but studies on its anti-neuroinflammatory and neuroprotective effect have not been deeply conducted. Thus, we investigated the anti-neuroinflammatory activity of JGT on lipopolysaccharide (LPS)-stimulated mouse microglia cells. Methods : To investigate the anti-neuroinflammatory effects of JGT on BV2 microglial cells, we examined the production of nitric oxide (NO) using griess assay, and mRNA expressions of pro-inflammatory cytokines such as interleukin (IL)-1𝛽, IL-6, and tumor necrosis factor (TNF)-𝛼 using real time RT-PCR. Furthermore, to determine the regulating mechanisms of JGT, we investigated the heme oxygenase (HO)-1 by real time RT-PCR. Results : Pre-treatment of JGT effectively decreased NO production in LPS-stimulated BV2 cells at concentrations without cytotoxicity. Additionally, JGT significantly suppressed the production of IL-1𝛽, IL-6, and TNF-𝛼 in LPS-stimulated BV2 cells. Furthermore, JGT activated the HO-1 expression, which is one of the immunomodulatory signaling molecules. And the abolishment of HO-1 by tin protoporphyrin IX (SnPP, the HO-1 inhibitor) reversed the anti- inflammatory activity of JGT in LPS-stimulated BV2 cells. Conclusions : Our results suggest that the JGT has anti-neuroinflammatory effect through the activation of HO-1 in LPS-stimulated BV2 cells. Thereby, JGT could expected to be used for the prevention and treatment of neurodegenerative disease related to neuroinflammation.

• 대한한의학회지
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• 제43권1호
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• pp.99-111
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• 2022

Objectives: Rehmanniae Radix Preparata (RRP) has been used as a traditional remedy to treat gynecology and endocrine diseases. Recently, studies on antioxidant and anti-inflammatory effects of RRP have been reported, so it was judged that RRP extracts would have an anti-depressive effect. Methods: We investigated the anti-neuroinflammatory and anti-depressive effect of RRP on lipopolysaccharide (LPS)-induced depression and LPS-stimulated BV2 microglia. RRP inhibited the LPS-stimulated excessive release of nitrite in the BV2 cells. RRP also significantly inhibited the inflammatory cytokines such as tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta and IL-6 in LPS-stimulated BV2 microglial cells. Results: RRP significantly suppressed the LPS-induced mitogen-activated protein kinase (MAPKs) and nuclear factor (NF)-𝜅B activation. In addition, administration of RRP not only inhibited the immobility time in the forced swimming test (FST) but also increased the total travel distance in the open field test (OFT). Also, RRP inhibited the elevation of TNF-alpha, IL-1beta, and IL-6 in brain of LPS-injected mice. Conclusions: Considering the overall results, our study showed that RRP exhibited the anti-neuroinflammatory and anti-depressive activities via deactivation of MAPKs and NF-𝜅B.

• 대한의생명과학회지
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• 제23권4호
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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.

• Biomolecules & Therapeutics
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• 제26권2호
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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.

• 한방재활의학과학회지
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• 제31권4호
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• pp.1-11
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• 2021

Objectives Hwanggeumjakyak-tang (HJT) has traditionally been used to treat gastrointestinal inflammatory diseases; however, its protective effects against neuronal inflammation are still undiscovered. Methods We investigated the anti-neuroinflammatory effects of HJT water extract on lipopolysaccharide (LPS)-stimulated BV2 mouse microglia cells. BV2 cells were treated with LPS (1 ㎍/mL) 1 hour prior to the addition of HJT. We measured cell viability using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and nitrite production using the Griess assay. We performed a reverse transcription-polymerase chain reaction assay to measure messenger RNA expression of inflammatory cytokines including interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α. Western blot analysis was performed to determine protein expression of mitogen-activated protein kinases (MAPKs) and inhibitor of nuclear factor kappa B (NF-κB)α. Results HJT inhibited excessive nitrite release in LPS-stimulated BV2 cells and also significantly inhibited inflammatory cytokines such as IL-1β, IL-6, and TNF-α in LPS-stimulated BV2 cells. Moreover, HJT significantly suppressed LPS-induced MAPK and NF-κB activation and inhibited the elevation of IL-1β, IL-6, and TNF-α in the brain of LPS-injected mice. Conclusions Our study highlights the anti-neuroinflammatory effects of HJT via MAPK and NF-κB deactivation.

• 대한본초학회지
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• 제39권5호
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• pp.31-38
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• 2024

Objectives : Achyranthes japonica Nakai (AJ) and Achyranthes bidentata Blume (AB) have been used without distinguishment. Moreover, comparative studies of AJ and AB on physiological activity in the organism levels remain fully understood. In this study, we aimed to evaluate and compare the effects of AJ and AB on anti-neuroinflammatory and neuroprotective effects. Methods : AJ and AB were extracted with distilled water (DW) and 70% ethanol (EtOH) extract. For the evaluation of anti-neuroinflammatory effects, we measured the production of nitric oxide (NO) in lipopolysaccharide (LPS)-treated BV2 microglial cells. To evaluate the neuroprotective effects, we assessed cell viability against toxicity, including hydrogen peroxide (H₂O₂), 6-hydroxydopamine (6-OHDA), and amyloid-beta (A𝛽), respectively, in PC12 or HT22 cells. Results : DW and 70% EtOH extracts of AJ and AB inhibited LPS-induced NO production in BV2 cells, with no significant differences between the origins and extraction solvents. Additionally, AJ and AB had no cytotoxicity, and exhibited the similar neuroprotective effects against H₂O₂ and 6-OHDA toxicities in PC12 cells, showing stronger activity in 70% EtOH extract compared to the DW extract. Furthermore, 70% EtOH extracts of AJ and AB protected neuronal cell against A𝛽 toxicity-induced cytotoxicity in HT22 cells. Conclusions : We demonstrated that AJ and AB have anti-neuroinflammatory and neuroprotective effects in the 70% EtOH extract compared to DW extract, with no significant differences between the species. These results suggested that AJ and AB would be the potential candidates for neurodegenerative diseases.

• 한국식품과학회지
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• 제53권3호
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• pp.296-303
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• 2021

본 연구에서는 국내에 자생하는 대나무 중 3종(왕대, 조릿대, 오죽)의 죽엽을 4종의 추출용매(물, 30% 주정, 70% 주정, 100% 주정)를 이용하여 추출 후 추출물별 항산화 활성 탐색, 신경염증 억제 효과 및 HPLC-UV 분석 방법에 의한 3가지 지표성분(caffeic acid, p-coumaric acid 및 Tricin)의 함량을 측정하였다. FRAP 방법과 DPPH 라디칼 및 ABTS 라디칼 소거능 측정방법을 이용하여 항산화 활성을 탐색하였으며, 3종의 대나무 중에서는 오죽 추출물이 총폴리페놀 및 총플라보노이드 함량이 가장 높았다. FRAP 방법, DPPH 라디칼 및 ABTS 라디칼 소거능 방법을 이용하여 항산화 활성을 측정한 결과 또한 오죽 추출물이 가장 우수하였다. Caffeic acid의 함량은 오죽의 물추출물이 6.247±0.049 ㎍/mg으로 가장 높았으며, p-coumaric acid의 함량은 오죽의 70% 주정추출물이 10.931±1.467 ㎍/mg으로 가장 높았으며 다음으로는 오죽의 100% 주정추출물이 9.374±1.140 ㎍/mg으로 높게 나타났으며 3종 죽엽의 물추출물을 제외한 주정추출물은 모두 p-coumaric acid 함량이 높음을 확인하였다. Tricin의 함량을 측정한 결과 또한 물추출물에서는 함량이 낮았으나, 70% 주정추출물이나 100% 주정추출물은 3종의 죽엽추출물 모두에서 3.094±0.875-5.233±2.698 ㎍/mg로 비슷한 함량을 나타내었다. LPS를 사용하여 미세아교세포의 활성화를 유도하여 신경염증반응의 지표인 NO의 생성량을 측정한 결과 3종의 죽엽추출물(70% 주정추출물) 모두 농도 의존적으로 NO의 생성량을 억제하였다. 따라서 본 연구의 결과는 죽엽추출물이 미세아교세포의 과도한 신경염증 활성화로 인해 발생되는 뇌 신경질환의 치료 소재로서 활용 가능성을 제시하였다.

• Journal of Microbiology and Biotechnology
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• 제28권1호
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• pp.12-21
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• 2018

Photorhabdus temperata (PT), a gram-negative bacterium, lives symbiotically within entomopathogenic nematodes. The insecticidal compounds derived from Photorhabdus are used as biopesticides in agriculture. However, the physiological properties are not well characterized. In the course of our screening for neuroprotective and anti-neuroinflammatory substances from natural products, the culture broth of PT showed considerable activities. By activity-guided purification, five anthraquinones, namely, 3-methoxychrysazine (1), 1,3-dimethoxy-8-hydroxy-9,10-anthraquinone (2), 1,3,8-trihydroxy-9,10-anthraquinone (3), 3,8-dihydroxy-1-methoxy-9,10-anthraquinone (4), and 1,3,4-trimethoxy-8-hydroxy-9,10-anthraquinone (5), were isolated from the ethyl acetate fraction of the PT culture broth. Among the isolated compounds, $75{\mu}M$ 3 significantly protected mouse hippocampal neuronal cells (HT22) against 5 mM glutamate-induced cell death via the inhibition of reactive oxygen species production, $Ca^{2+}$ influx, and lipid peroxidation. Additionally, 3 and 4 effectively suppressed the interferon-${\gamma}$-induced neuroinflammation of mouse-derived microglial cells (BV2) at 10 ng/ml, via the reduction of nitric oxide, interleukin-6, and tumor necrosis factor-${\alpha}$. Anthraquinones 3 and 4 derived from the PT culture broth are a potential starting point to discover neuroprotective and anti-neuroinflammatory drug leads. The novel compound 5 is reported for the first time in this study.

• 생약학회지
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• 제52권4호
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• pp.212-218
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• 2021

Fatsia japonica is grown wild to Eastern Asia, including Korea, Japan, and Taiwan and it is known as ornamental plant, and it is also known that pharmacological action. In this study, we have selected the stem of F. japonica with consideration about biological activities and amount of yield. In addition, four compounds (1-4) were isolated from the stem of F. japonica. Extensive spectroscopic and chemical studies established the structures of these compounds as maltose (1), begoniifolide A (2), leiyemudanoside B (3), leonticin F (4). All of the compounds were investigated for their anti-inflammatory, anti-neuroinflammatory, and neuro-protective effects on RAW264.7, BV2, and HT22 cells. However, among four compounds, there were no effects by maltose (1), begoniifolide A (2), leiyemudanoside B (3), leonticin F (4) on the anti-inflammatory, anti-neuroinflammatory, and neuro-protective action. This is the first report on the isolation of maltose (1), begoniifolide A (2), leiyemudanoside B (3), leonticin F (4) from the stem of F. japonica. Begoniifolide A (2), leiyemudanoside B (3), leonticin F (4) were isolated for the first time from this plant. It might be necessary to continue the further studies to find the biological active compounds isolated from the stem of F. japonica.