• 제목/요약/키워드: Anti-dementia

검색결과 98건 처리시간 0.027초

Neuronal injury in AIDS dementia: Potential treatment with NMDA open-channel blockers and nitric oxide-related species

  • Lipton, Stuart A.
    • 한국응용약물학회:학술대회논문집
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    • 한국응용약물학회 1996년도 춘계학술대회
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    • pp.19-29
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    • 1996
  • The neurological manifestations of AIDS include dementia, encountered even in the absence of opportunistic superinfection or malignancy. The AIDS Dementia Complex appears to be associated with several neuropathological abnormalities, including astrogliosis and neuronal injury or loss. How can HIV-1 result in neuronal damage if neurons themselves are only rarely, if ever, infected by the vitus\ulcorner In vitro experiments from several different laboratiories have lent support to the existence of HIV- and immune-related toxins. In one recently defined pathway to neuronal injury, HIV-infected macrophages/microglia as well as macrophages activated by HIV-1 envelope protein gp120 appear to secrete excitants/neurotoxins. These substances may include arachidonic acid, platelet-activating factor, free radicals (NO - and O$_2$), glutamate, quinolinate, cysteine, cytokines (TNF-${\alpha}$, IL1-B, IL-6), and as yet unidentified factors emanating from stimulated macrophages and possibly reactive astrocytes. A final common pathway for newonal suscepubility appears to be operative, similar to that observed in stroke, trauma, epilepsy, and several neurodegenerative diseases, including Huntington's disease, Parkinson's disease, and amyotrophic lateral sclerosis. This mechanism involves excessive activation of N-methyl-D-aspartate (NMDA) receptor-operated channels, with resultant excessive influx of Ca$\^$2+/ leading to neuronal damage, and thus offers hope for future pharmacological intervention. This chapter reviews two clinically-tolerated NMDA antagonists, memantine and nitroglycerin; (ⅰ) Memantine is an open-channel blocker of the NMDA-associated ion channel and a close congener of the anti-viral and anti-parkinsonian drug amantadine. Memantine blocks the effects of escalating levels of excitotoxins to a greater degree than lower (piysiological) levels of these excitatory amino acids, thus sparing to some extent normal neuronal function. (ⅱ) Niuoglycerin acts at a redox modulatory site of the NMDA receptor/complex to downregulate its activity. The neuroprotective action of nitroglycerin at this site is mediated by n chemical species related to nitric oxide, but in a higher oxidation state, resulting in transfer of an NO group to a critical cysteine on the NMDA receptor. Because of the clinical safety of these drugs, they have the potential for trials in humans. As the structural basis for redox modulation is further elucidated, it may become possible to design even better redox reactive reagents of chinical value. To this end, redox modulatory sites of NMDA receptors have begun to be characterized at a molecular level using site-directed mutagenesis of recombinant subunits (NMDAR1, NMDAR2A-D). Two types of redox modulation can be distinguished. The first type gives rise to a persistent change in the functional activity of the receptor, and we have identified two cysteine residues on the NMDARI subunit (#744 and #798) that are responsible for this action. A second site, presumably also a cysteine(s) because <1 mM N-ethylmaleimide can block its effect in native neurons, underlies the other, more transient redox action. It appears to be at this, as yet unidentified, site on the NMDA receptor that the NO group acts, at least in recombinant receptors.

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몇 가지 채소와 약용 식물을 이용하여 제조한 식물 복합 추출물의 영양학적 특성과 생리기능성 (Nutritional Characteristics and Physiological Functionalities of Polyplant Extracts from Some Vegetables and Medicinal Plants)

  • 김현경;이은나;금종화;이종수
    • 한국식품영양학회지
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    • 제21권4호
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    • pp.410-415
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    • 2008
  • The nutritional characteristics and functionalities of the polyplant extracts(PPE) from the extraction of various plants were assessed for the development of a new functional food. The PPE contained 42.95 g of glucose, 22.61 g of fructose, and 12.48 g of sucrose per 100 g of PPE as free sugar, and its reducing sugar contents was measured at 480.6 mg per g of PPE. Among free amino acids, proline contents was the highest at 0.58 g per 100 g of PPE, and it contained only 12.65 mg of malic acid and 6.92 mg of tartaric acid per g of PPE as an organic acid. The antioxidant activity of PPE was the highest at 91.6%, whereas SOD-like activity and xanthin oxidase inhibitory activity, which are associated with anti-aging effects, were 21.6% and 9.3%, respectively. HMG-CoA reductase inhibitory activity was 10.0% and anti-dementia acetylcholinesterase inhibitory activity was quite low(5.1%).

납작파래(Enteromorpha compressa) 추출물의 항산화성 및 생리활성 (Comparison of the Antioxidant and Physiological Activities of Different Solvent Extracts Derived from Enteromorpha compressa)

  • 최지원;박선아;김원석;김용태
    • 한국수산과학회지
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    • 제57권2호
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    • pp.137-144
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    • 2024
  • In this study, we investigated the antioxidant and physiological activities of the Korean marine algae, Enteromorpha compressa. Solvent extracts of E. compressa were prepared using 70% ethanol, 80% methanol, and water, with extraction yields ranging from 9.55% to 25.67%. The total polyphenol and flavonoid contents ranged from 20.76-28.41 mg/g and 2.56-18.59 mg/g, respectively. Compared with the water extract, the ethanol and methanol extracts were found to have higher antioxidant activities. All three extracts were found to promote alcohol dehydrogenase and aldehyde dehydrogenase activities in a concentration-dependent manner, whereas the methanol and ethanol extracts were established to have the highest angiotensin-converting enzyme (ACE) inhibitory activity (IC50=1.40 ㎍/mL) and β-secretase inhibitory activity (IC50=0.17 ㎍/mL), respectively. These findings thus indicate that E. compressa could have beneficial application as a supplementary antioxidant and functional constituent in food and pharmaceutical materials.

pCT105로 유도된 치매모델에서 석창포(石菖蒲) 수추출액(水抽出液)이 미치는 영향 (The effects of Rhizoma Acori Graminei water extract in Alzheimer's Disease Model induced by pCT105)

  • 최혁;김상호;이대용;안대종;강형원;류영수
    • 동의신경정신과학회지
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    • 제13권2호
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    • pp.173-194
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    • 2002
  • Alzheimer's disease(AD) is a geriatric dementia that is widespread in old age. In the future AD will be the largest problem in public health service. From old times, Much medicines have been used for treatment of dementia, but there is no medicine having obvious effect. AD is one of brain retrogression disease. So We studied on herbal medicine that have a relation of brain retrogression. From old times, In Oriental Medicine, Rhizoma Acori Graminei has been used for disease in relation to brain retrogression. We studied on the effects of anti-Alzheimer in pCT105-induced neuroblastoma cell lines by Rhizoma Acori Graminei extract As the result of this study, In RAG group, the apoptosis in the nervous system is inhibited, the repair against the degerneration of Neuroblastoma cells by CT105 expression is promoted. These results indicate that RAG possess strong inhibitory effect of apoptosis in the nervous system and repair effect against the degeneration of Neuroblastoma cells by CT105 expression.

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홍삼(紅蔘) 수추출물(水抽出物)이 치매조백질(痴呆蚤白質) APP 형질전환(形質轉換) 초파리에 미치는 영향(影響) (Study of anti-Alzheimer Activities from Ginseng Radix Rubra Water Extract by Alzheimer's Protein APP-transgenic Fly)

  • 김영준;김진형;윤종현;정은영;김태헌;유영수;강형원
    • 동의신경정신과학회지
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    • 제20권1호
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    • pp.235-247
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    • 2009
  • Objectives : Ginseng Radix Rubra water extract(RGE) has been used in vivo test for its beneficial effects on neuronal survival and neuroprotective functions, particularly in connection with APP-related dementias and Alzheimer's disease (AD). APP derived from proteolytic processing of the ${\beta}$-amyloid precursor protein (APP), including the amyloid-${\beta}$ peptide (A${\beta}$), plays a critical role in the pathogenesis of Alzheimer's dementia. Methods : We determined that RGE inhibits formation of APP, which are the behavior, and possibly causative, feature of AD. Results and Conclusions : In the cells, RGE significantly activated antiapoptosis and decreased the activity of APP-grim, a key enzyme in the apoptosis cell-signaling cascade. These results suggest that neuronal damage in AD might be due to two factors: a direct APP toxicity and multiple cellular and molecular neuroprotective mechanisms, including attenuation of apoptosis and direct inhibition of APP, underlie the neuroprotective effects of RGE.

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Interaction of HIV-1 Core p24 Antigen with Human Monocytic Cell Line THP1 Results in TNF-${\alpha}$ Dependent Secretion of Matrix Metalloproteinase-9

  • Sung, Ji-Hye;Yoo, Seung-Hee;Park, Hae-Kyung;Chong, Young-Hae
    • 대한미생물학회지
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    • 제35권1호
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    • pp.9-18
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    • 2000
  • Immunological mechanisms involving the release of inflammatory factors by HIV-1 infected microglia in the brain have been implicated in the pathogenesis of HIV dementia (HIVD). Since the regulation of matrix metalloproteinases (MMPs) activity can be influenced by variety of inflammatory mediators, this study was undertaken to look for a correlation between the MMP-9 release and the production of TNF-${\alpha}$ in response to HIV-1 p24 in the human monocyte cell line THP-1 as a model for microglia. First, it was shown that HIV-l core p24 antigen induced THP-1 to secrete MMP-9 in a dose response manner while it elicited a little effect on MMP-2 release in human astroglial cell line T98G. Next, it was found that p24 induced THP-1 to secrete TNF-${\alpha}$ without prior differentiation into macrophages by phorbol myristate acetate (PMA) treatment. Furthermore, anti-TNF-${\alpha}$ neutralizing antibodies significantly blocked p24-induced MMP-9 release in a dose dependent manner. Our data indicate that p24 antigen induces monocytic MMP-9 release by triggering up-regulation of TNF-${\alpha}$ secretion.

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원지(遠志)와 석창포(石菖蒲)의 단독 및 혼합추출액이 CT105 로 유도된 신경세포암 세포주에 미치는 영향 (Comparative effects of Radix Polygalae and Rhizoma Acori Graminei on CT105-induced neuroblastoma cell lines)

  • 한원주;김형수;김상태;김태헌;류영수;강형원
    • 동의신경정신과학회지
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    • 제14권2호
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    • pp.95-105
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    • 2003
  • Alzheimer's disease(AD) is a geriatric dementia that is widespread in old age. In the future AD will be the largest problem in public health service. From old times, Much medicines have been used for treatment of dementia, but there is no medicine having obvious effect. AD is one of brain retrogression disease. So We studied on herbal medicine that have a relation of brain retrogression. From old times, In Oriental Medicine, Radix Polygalae and Rhizoma Acori Graminei have been used for disease in relation to brain retrogression. We studied of anti-Alzheimer effect on CT105-induced neuroblastoma cell lines by Radix Polygalae(RP) and Rhizoma Acori Graminei(RAG) water extract. As the result of this study, In RP and RAG group, the apoptosis in the nervous system is inhibited, the repair against the degeneration of Neuroblastoma cells by CT105 expression is induced. These results indicate that In RP and RAG, RAG possess the strongest in inhibitory effect of apoptosis in the nervous system and repair effect against the degeneration of Neuroblastoma cells by CT105 expression.

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RAW 264.7 대식세포에서 청뇌명신환(淸腦明神丸)에 의한 염증성 및 산화적 스트레스 반응 억제 효능 (Anti-inflammatory and Antioxidant Effects of Cheongnoimyungshin-hwan in RAW 264.7 Macrophages)

  • 손변우;이명화;황원덕
    • 대한한의학방제학회지
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    • 제26권1호
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    • pp.1-12
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    • 2018
  • Objectives : Cheongnoimyungshin-hwan (CNMSH) is a Herbal compound prescription that is composed mainly of herbal medicines such as Ginseng Radix Alba, Angelicae Gigantis Radix, Dioscoreae Rhizoma, Longan Arillus and cornus cervi parvum, and for the purpose of improving memory and preventing dementia. Methods : In this study, it was investigated whether CNMSH could suppress inflammatory response and oxidative stress in the lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells. As a result, CNMSH decreased expression of inducible nitric oxide (NO) synthase and cyclooxygenase-2, and also inhibited production of NO, prostaglandin E2. Results : This effect was associated with the suppression of the expression of p65, one of the nuclear factor-kappaB ($NF-{\kappa}B$) subunits, and increased expression of $I{\kappa}B-{\alpha}$, inhibit the $NF-{\kappa}B$ transcription factor. In addition, CNMSH significantly blocked intracellular reactive oxygen species accumulation in response to LPS stimulation. Furthermore, CNMSH increased expression of nuclear factor erythroid 2-related factor (Nrf)-2 activation and heme oxygenase (HO)-1. Conclusions : Therefore, it has been shown anti-inflammatory and antioxidant effects by inhibiting the expression and production of inflammatory mediators in LPS-stimulated macrophages, and is associated with ROS generation and is activated by Nrf2/HO-1 signaling pathway.

식품학적 가공에 의한 생약의 성분 및 활성 변화 IV - Roasting처리에 의한 진피 중 5-HMF 함량증가 - (Changes in Chemical Composition and Biological Activities of Oriental Crude Drugs by Food Processing Techniques IV - Increase in 5-HMF Content of Aurantii nobilis Pericarpium During Roasting Process -)

  • 예근학;허종문;최선하;양은주;이유미;강영화;송경식
    • 생약학회지
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    • 제38권2호통권149호
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    • pp.133-138
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    • 2007
  • Regarding chemical changes in oriental drugs after food processing such as roasting, fermentation, and extrusion, fifty commonly-used medicinal plants were investigated. As a result, Aurantii nobilis Pericarpium (a tangerine peel from Citrus unshu Markovich) showed remarkably different HPLC profiles after being roasted. An increased peak was isolated by repeated chromatography and identified as 5-hydroxymethyl furfral (5-HMF) by means of instrumental analyses. The 5-HMF content of Aurantii nobilis Pericarpoum reached its maximum level after being roasted for 30 min at 225$^{\circ}C$ (49.2 mg/g extract, ca 42 times of increase over untreated control). Although there were no significant changes in in vitro biological activity such as antioxidative, anti-dementia, anti-hypertension, anti-coagulation, or cytotoxicity, before and after roasting process, our results suggested that simple heat treatment might improve the value of the above oriental drug since 5-HMF has been known to possess inhibitory activities toward nitric oxide formation, tyrosinase, and sickling of red blood cells.

Sodium Cyanide로 유도된 신경아세포종 세포주에서 오수유의 신경상해 보호효과 (Anti-neuronal Injury Effect of Evodiae Fructus Water Extract in Sodium Cyanide-induced SK-N-SH Cell Lines)

  • 장우석;이소연;윤현덕;신오철;박창국;박치상
    • 대한한의학회지
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    • 제26권3호
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    • pp.135-145
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    • 2005
  • Objectives : This study investigated effect of Evodiae fructus water extract (EVOR) on apoptotic cell death induced by NaCN in SK-N-SH neuroblastoma cell lines. NaCN stimulates glutamate release which can activate glutamate receptors to initiate excitotoxic processes. This study examines the role of EVOR in mediating NaCN-induced cytotoxicity. Methods & Results : Cytotoxicity was assessed by measuring lactate dehydrogenase (LDH) in the culture media. NaCN(0.1mM) produced cytotoxicity following 12hrs of incubation. NaCN-induced cytotoxicity was partially blocked by EVOR. The treatment of EVOR in simultaneous exposure of cultures to NaCN provided complete protection against cytotoxicity. NaCN-induced cytotoxicity was found to inhibit DNA fragmentation, repaired by cell cycle and simultaneous exposure to NaCN, regenerated with neurite outgrowh by EVOR. These results indicate thaf damage by NaCN in neumnal cell cultures was repaired by EVOR, whereas NaCN-induced cytotoxicity is blocked Primarily by activation of anti-apoptosis. Conclusions : These results suggest that EVOR may be beneficial for the treatment of dementia and other degenerative problems of the central nervous system.

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