• 한국응용과학기술학회지
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• 제36권2호
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• pp.468-478
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• 2019

본 연구는 동충하초 추출물을 PC12 및 BV2 세포에서 인지능력 개선에 대한 효능을 평가하고자 하였다. 동충하초 추출물을 증류수로 추출하여 PC12 및 BV2 세포로 MTT 분석을 통해 세포 생존율을 확인하고 L-glutamate로 유도한 PC12 세포를 통해 세포 보호 효능과 아세틸콜린 함량 및 아세틸콜린에스테아제 활성을 평가하였다. 또한, LPS로 유도한 BV2 세포를 통해 nitric oxide (NO) 및 prostaglandin E2 (PGE2) 생성량 등의 항염증 효능을 측정하고 western blot 분석을 통해 $NK-{\kappa}B$, p38, JNK, caspase-3 등의 단백질 발현량을 확인하였다. 동충하초 추출물은 $200{\mu}g/m{\ell}$ 농도를 제외하고 1, 10, $100({\mu}g/m{\ell})$ 농도에서 세포 독성이 나타나지 않았다. L-glutamate로 유도한 PC12 세포에서 유의성있게 세포 보호 효능과 아세틸콜린 함량의 증가, 아세틸콜린에스테아제 활성 감소가 나타났다. 또한, 동충하초 추출물은 NO 및 PGE2 생성량과 $NK-{\kappa}B$, p38, JNK, caspase-3 등의 단백질 발현을 억제하였다. 이와 같은 결과는 동충하초 추출물이 인지능력에 대한 예방 및 개선 효능이 있음을 나타낸다. 따라서 동충하초 추출물은 인지능력 개선을 위한 새로운 천연 소재로 활용될 수 있다.

• Journal of Korean Neurosurgical Society
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• 제30권6호
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• pp.688-698
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• 2001

Objectives : Parkinson's disease is a well-known neurodegenerative disease characterized by dopaminergic cell death in the substantia nigra. The reactive gliosis by activated astrocytes and microglias is no more regarded as a simple sequel of neuronal cell death. Microglial activation takes place in a stereotypic pattern with graded morphologic and functional(resting, activated and phagocytic) changes. In Parkinson's disease animal model, the degree of microglial activation along the nigro-striatal dopaminergic tract has not been studied intensively. The purpose of this study was to elucidate the characteristics of microglial reaction and to grade its degree of activation at substantia nigra and corpus striatum using 6-hydroxydopamine induced rat model of Parkinson's disease. Methods : Using Sprague-Dawley rat, parkinsonian model was made by 6-hydroxydopamine(OHDA) induced destruction of medial and lateral substantia nigra(SN). The rat was sacrificed 3-, 5-, 7-, 14- and 21-day-after operation. For control group, we injected saline with same manner and sacrificed 3-day after operation. With immunohistochemistry, we examined dopaminergic neuronal cells and microglial expression using tyrosine hydroxylase (TH) and OX-42 antibodies, respectively. Also we performed in situ hybridization for osteopontin, a possible marker of subset in activated microglia. Results : 1) In lesioned side of substantia nigra and corpus striatum, the TH immunoreactivity was markedly decreased in whole experimental groups. 2) Using optical densitometry, microglia induced immunoreactivity of OX-42 was counted at SN and corpus striatum. At SN, it was increased significantly on the lesioned side in control and all time-dependent experimental groups. At striatum, it was increased significantly in post lesion 3-day group only(p <0.05). Compared to control group, immunoreactivity of OX-42 on lesioned side was increased in groups, except post lesion 21-day group, at SN. Only post lesion 3-day group showed significance at striatum(p <0.05). Compared to SN region, immunoreactivity of OX-42 was much weaker in striatum. 3) Microscopically, the microglias showed typically different activation pattern. At SN, numerous phagocytic microglias were found at pars compacta and reticularis of lesion side. At striatum, no phagocytic form was found and the intensity of staining was much weaker. 4) At SN, the immunoreactivity of osteopontin showed definite laterality and it was markedly increased at pars compacta of lesion side with relatively short duration time. At striatum, however, it was not detected by in situ hybridization technique. Conclusion : The nigral 6-OHDA induced rat model of Parkinson's disease revealed several characteristic patterns of microglial reaction. At SN, microglias was activated shortly after direct neuronal damage and maintained for about three weeks. In contrast, despite of sufficient dopaminergic insufficiency at striatum, activation of microglias was trivial, and distinguished 3 day later. Antegrade slow neuronal degeneration is major pathophysiology in striatal dopaminergic deficiency. So, the acuteness of neuronal damage and consequential degree of neuronal degeneration may be important factor for microglial activation in neurodegenerative diseases such as Parkinson's disease. Additionally, osteopontin may be a possible marker for several subsets of activated microglia, possibly the phagocytic form.

• Molecules and Cells
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• 제43권5호
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• pp.431-437
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• 2020

The hypothalamus is a crucial organ for the maintenance of appropriate body fat storage. Neurons in the hypothalamic arcuate nucleus (ARH) detect energy shortage or surplus via the circulating concentrations of metabolic hormones and nutrients, and then coordinate energy intake and expenditure to maintain energy homeostasis. Malfunction or loss of hypothalamic ARH neurons results in obesity. Accumulated evidence suggests that hypothalamic inflammation is a key pathological mechanism that links chronic overconsumption of a high-fat diet (HFD) with the development of obesity and related metabolic complications. Interestingly, overnutrition-induced hypothalamic inflammation occurs specifically in the ARH, where microglia initiate an inflammatory response by releasing proinflammatory cytokines and chemokines in response to excessive fatty acid flux. Upon more prolonged HFD consumption, astrocytes and perivascular macrophages become involved and sustain hypothalamic inflammation. ARH neurons are victims of hypothalamic inflammation, but they may actively participate in hypothalamic inflammation by sending quiescence or stress signals to surrounding glia. In this mini-review, we describe the current state of knowledge regarding the contributions of neurons and glia, and their interactions, to HFD-induced hypothalamic inflammation.

• Archives of Pharmacal Research
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• 제28권2호
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• pp.216-219
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• 2005

Wogonin (5,7-dihydroxy-8-methoxyflavone) has been reported to exhibit a variety of biological properties including anti-inflammatory and neuroprotective functions. In this study, biological activities of diverse synthetic wogonin derivatives have been evaluated in two experimental cell culture models. Inhibitory activities of wogonin derivatives on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in BV2 microglial cells and on hydrogen peroxide ($H_{2}O_2$)-induced neuronal cell death in SH-SY5Y human neuroblastoma were examined. Wogonin derivatives such as WS2 and WS3 showed more potent suppressive activities on LPS-induced NO production and $H_{2}O_2$-induced cytotoxicity than wogonin itself. In addition, thiol substitution played a minor role in enhancing the activities of the derivatives. These findings may contribute to the development of novel anti-inflammatory and neuroprotective agents derived from wogonin.

• 대한의생명과학회지
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• 제26권2호
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• pp.109-113
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• 2020

Dangyuja (Citrus maxima (Burm.) Merr.) is a native fruit of great economic importance in Jeju island in Korea. To provide experimental evidence for the antioxidant and anti-inflammation properties on extraction ethanol concentration of Dangyuja, 2 cultivars, including 30-year-old and 120-year-old were evaluated. 30-year-old Dangyuja 50%, 70% ethanol extracts had the highest polyphenol and flavonoid content, and the strongest 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging activity. To investigate the anti-inflammatory activity of Dangyuja ethanol extracts, we used BV-2 microglia cells and induced inflammation using lipopolysaccharide (LPS). Then, we measured levels of inflammatory mediators as nitric oxide (NO). Among the 6 extracts, 30-year-old Dangyuja 50% ethanol extracts show the highest anti-inflammatory activity. The results suggest that 30-year-old Dangyuja 50% ethanol extracts provides significant health benefits and may be used for developing new functional materials.

• BMB Reports
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• 제53권1호
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• pp.20-27
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• 2020

Translocator protein (TSPO), also known as peripheral benzodiazepine receptor, is a transmembrane protein located on the outer mitochondria membrane (OMM) and mainly expressed in glial cells in the brain. Because of the close correlation of its expression level with neuropathology and therapeutic efficacies of several TSPO binding ligands under many neurological conditions, TSPO has been regarded as both biomarker and therapeutic target, and the biological functions of TSPO have been a major research focus. However, recent genetic studies with animal and cellular models revealed unexpected results contrary to the anticipated biological importance of TSPO and cast doubt on the action modes of the TSPO-binding drugs. In this review, we summarize recent controversial findings on the discrepancy between pharmacological and genetic studies of TSPO and suggest some future direction to understand this old and mysterious protein.

• Archives of Pharmacal Research
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• 제27권7호
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• pp.751-756
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• 2004

Flavonoids have been demonstrated to exhibit a wide range of biological activities including anti-inflammatory and neuroprotective actions. Although a significant amount of flavonoids has been identified to be present as glycosides in medicinal plants, determinations of the biological activities of flavonoids were mainly carried out with aglycones of flavonoids. Therefore, the exact role of the glycosidation of flavonoid aglycones needs to be established. In an attempt to understand the possible role of glycosidation on the modulation of the biological activities of flavonoids, diverse glycosides of kaempferol, quercetin, and aromadendrin were examined in terms of their anti-inflammatory activity determined with the suppression of lipopolysaccharide (LPS)-induced nitric oxide (NO) production in BV2 microglial cells. The results indicated that glycosidation of aglycones attenuated the suppressive activity of aglycones on LPS-induced NO production. Although attenuated, some of glycosides, depending on the position and degree of glycosidation, maintained the inhibitory capability of LPS-induced NO production. These findings suggest that glycosidation of flavonoid aglycones should be considered as an important modulator of the biological activities of flavonoids.

• BMB Reports
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• 제43권4호
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• pp.225-232
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• 2010

Parkinson's Disease (PD) is a common neurodegenerative disease characterized by the progressive degeneration of nigrostriatal dopaminergic (DA) neurons. Although the causative factors of PD remain elusive, many studies on PD animal models or humans suggest that glial activation along with neuroinflammatory processes contribute to the initiation or progression of PD. Additionally, several groups have proposed that dysfunction of the blood-brain barrier (BBB) combined with infiltration of peripheral immune cells play important roles in the degeneration of DA neurons. However, these neuroinflammatory events have only been investigated separately, and the issue of whether these phenomena are neuroprotective or neurotoxic remains controversial. We here review the current knowledge regarding the functions of these neuroinflammatory processes in the brain. Finally, we describe therapeutic strategies for the regulation of neuroinflammation with the goal of improving the symptoms of PD.

• 대한한의학회지
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• 제39권3호
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• pp.1-16
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• 2018

Objectives: The purpose of this study was to investigate the effects of 56 herbal formulae covered by the National Health Insurance Corporation (NHIC) on dementia-related biomarkers and neuronal cell changes. Methods: The 56 herbal formulae were extracted with 70% ethanol at $100^{\circ}C$ for 2 h. The antioxidant properties was measured by radical scavenging assay using ABTS+ radical. The acetylcholinesterase (AChE) activity was tested by Ellman's assay and $amyloid-{\beta}$ ($A{\beta}$) aggregation was determined using fluorescence method. To estimate the inhibitory effects of herbal formulae on neuronal cell death and inflammation using HT22 hippocampal cells and BV-2 microglia, respectively. Results: Among the 56 herbal formulae, Dangguiyukhwangtang, Banhasasimtang, Samhwangsasimtang, Cheongwiesan, Hwangryunhaedoktang, Banhabaekchulchunmatang, Jaeumganghwatang, Cheongseoikgitang, and Hoechunyanggyuksan has a significant inhibitory effects on acetylcholinesterase (AChE) activity. Doinseunggitang and Samhwangsasimtang exerted the effect on the inhibition of $amyloid-{\beta}$ ($A{\beta}$) aggregation. Additionally, 10 herbal formulae affected AChE and $A{\beta}$ aggregation revealed antioxidant activity as well as neuroprotective and anti-neuroinflammation effects in neuronal cell lines. Conclusions: 10 herbal formulae that have been shown to be effective against the major dementia markers have been shown to have antioxidant activity, neuronal cell protection and inhibition of brain inflammation. Further investigation of these herbal formulae will need to be validated in dementia animal models.

• Natural Product Sciences
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• 제24권2호
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• pp.132-138
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• 2018

Phytochemical investigation of 80% MeOH extract of the aerial parts of Capsella bursa-pastoris yielded fourteen compounds (1 - 14). The structures of the compounds were elucidated by spectroscopic methods to be methyl-1-thio-${\beta}$-D-glucopyranosyl disulfide (1), 10-methylsulphinyl-decanenitrile (2), 11-methyl-sulphinyl-undecanenitrile (3), 1-O-(lauroyl)glycerol (4), phytene-1, 2-diol (5), (3S,5R,6S,7E)-5,6-epoxy-3-hydroxy-7-megastigmen-9-one (6), loliolide (7), ${\beta}$-sitosterol (8), 3-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-1-propanone (9), 1-feruloyl-${\beta}$-D-glucopyranoside (10), pinoresinol-4'-O-${\beta}$-D-glucopyranoside (11), luteolin (12), quercetin-3-O-${\beta}$-D-glucopyranoside (13), and luteolin 6-C-${\beta}$-glucopyranoside (14). Although compound 1 was reported as synthetic compound, 1 was first isolated from natural source. NMR spectral data assignments of 1, 2 and 3 were reported for the first time, and compounds 1 - 14 were for the first time reported from this plant source. The anti-inflammatory effects of 1 - 14 were evaluated in lipopolysaccharide (LPS)-stimulated murine microglia BV-2 cells. Compounds 12 exhibited strong inhibitory effects on nitric oxide production in LPS-activated BV-2 cells with $IC_{50}$ values of $9.70{\mu}M$.