Morinda citrifolia (noni) fruit juice has exhibited a variety of biological activities in human clinical trials, indicating that it influences multiple systems of the body. Since the 1990s, the endocannabinoid system ...Morinda citrifolia (noni) fruit juice has exhibited a variety of biological activities in human clinical trials, indicating that it influences multiple systems of the body. Since the 1990s, the endocannabinoid system (ECS) has been found to modulate the activity of other organ systems. To investigate noni’s potential impact on the ECS, extracts from freeze-dried noni fruit were evaluated in fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) inhibition assays. The ethyl acetate extract demonstrated the greatest activity against both enzymes. Lignans in this extract also inhibited enzyme activities, with americanin A being the most active in both assays. Americanoic acid and 3,3’-bisdemethylpinoresinol were the next most active compounds. These results suggest that lignans in noni fruit may influence endocannabinoid levels within the body via FAAH and MAGL inhibition. This reveals another set of probable mechanisms of action by which noni juice affects human health.展开更多
Background:The expression,localization,and function of the endocannabinoid system has been well characterized in recent years in the monkey retina and in the primary thalamic relay,the lateral geniculate nucleus(dLGN)...Background:The expression,localization,and function of the endocannabinoid system has been well characterized in recent years in the monkey retina and in the primary thalamic relay,the lateral geniculate nucleus(dLGN).Few data are available on cortical recipients’structures of the dLGN,namely the primary visual cortex(V1).The goal of this study is to characterize the expression and localization of the metabotropic cannabinoid receptor type 1(CB1R),the synthesizing enzyme N-acyl phosphatidyl-ethanolamine phospholipase D(NAPE-PLD),and the degradation enzyme fatty acid amide hydrolase(FAAH)in the vervet monkey area V1.Methods:Using Western blots and immunohistochemistry,we investigated the expression patterns of CB1R,NAPE-PLD,and FAAH in the vervet monkey primary visual cortex.Results:CB1R,NAPE-PLD,and FAAH were expressed in the primary visual cortex throughout the rostro-caudal axis.CB1R showed very low levels of staining in cortical layer 4,with higher expressions in all other cortical layers,especially layer 1.NAPE-PLD and FAAH expressions were highest in layers 1,2 and 3,and lowest in layer 4.Conclusions:Interestingly enough,CB1R was very low in layer 4 of V1 in comparison to the other cortical layers.The visual information coming from the dLGN and entering layer 4Calpha(magno cells)and 4Cbeta(parvo cells)may be therefore modulated by the higher expression levels of CB1R in cortical layers 2 and 3 on the way to the dorsal and ventral visual streams.This is further supported by the higher expression of NAPE-PLD and FAAH in the outer cortical layers.These data indicate that CB1R system can influence the network of activity patterns in the visual stream after the visual information has reached area V1.These novel results provide insights for understanding the role of the endocannabinoids in the modulation of cortical visual inputs,and hence,visual perception.展开更多
Background:The goal of this study is to determine the expression and localization of the cannabinoid receptor type 1(CB1R),the synthesizing enzyme N-acyl phosphatidyl-ethanolamine phospholipase D(NAPE-PLD),and the deg...Background:The goal of this study is to determine the expression and localization of the cannabinoid receptor type 1(CB1R),the synthesizing enzyme N-acyl phosphatidyl-ethanolamine phospholipase D(NAPE-PLD),and the degradation enzyme fatty acid amide hydrolase(FAAH)in the vervet monkey area V1 to better understand the mechanisms underlying the effects of eCB system modulation on cortical visual processing.Methods:Using Western blots and immunohistochemistry,we investigated the laminar and cellular expression patterns of CB1R,NAPE-PLD,and FAAH across the rostrocaudal axis of the vervet monkey(Chlorocebus sabaeus)primary visual cortex.Results:CB1R,NAPE-PLD,and FAAH were expressed in V1 throughout the rostrocaudal axis.CB1R showed very low staining in layer(L)4,with higher expression in all other layers,especially L1,followed by L2 and L3.NAPE-PLD and FAAH expression patterns were similar,but not quite as low in L4.CB1R,NAPE-PLD,and FAAH were localized in vGlut2-positive cells,representing glutamatergic projection neurons,and in somatostatin(SST)-positive cells,a class of GABAergic interneurons.Conclusions:The low level of CB1R in L4 indicates less direct endocannabinoid modulation of V1 afferents from the dLGN,but that greater modulation may occur via the higher expression of CB1R in L2 and L3 on the way to the dorsal and ventral visual streams.This is further supported by the higher expression of NAPE-PLD and FAAH in these layers.Expression in vGlut2-positive and SST-positive cells represents a role at both glutamatergic and GABAergic neurons.These data indicate that CB1R may influence the network of activity patterns in the visual streams after the visual information has reached V1,and thus may influence visual perception.展开更多
背景:内脏感觉过敏是功能性胃肠病的重要病理生理机制之一,快眼动(REM)睡眠剥夺可降低大鼠内脏感觉,但具体机制尚不明。目的:研究外周内源性大麻素系统在REM睡眠剥夺所致大鼠内脏感觉降低中的作用。方法:24只雄性Sprague-Dawley大鼠随...背景:内脏感觉过敏是功能性胃肠病的重要病理生理机制之一,快眼动(REM)睡眠剥夺可降低大鼠内脏感觉,但具体机制尚不明。目的:研究外周内源性大麻素系统在REM睡眠剥夺所致大鼠内脏感觉降低中的作用。方法:24只雄性Sprague-Dawley大鼠随机分为实验对照组、睡眠剥夺组和利莫那班干预组。采用花瓶技术制作REM睡眠剥夺大鼠模型。睡眠剥夺48 h后行结直肠扩张(CRD),记录腹壁肌电图,以反映内脏感觉功能的变化。采用逆转录聚合酶链反应(RT-PCR)和蛋白质印迹法分别测定大鼠肠道组织中1型大麻素(CB1)受体、脂肪酰胺水解酶(FAAH)和单酰基甘油脂酶(MAGL)mRNA和蛋白表达。结果:予不同扩张压力(40、60和80 mm Hg)后,睡眠剥夺组大鼠腹外斜肌放电次数显著低于实验对照组(P<0.05);利莫那班干预组放电次数显著高于睡眠剥夺组(P<0.05),但与实验对照组无明显差异。与实验对照组相比,睡眠剥夺组大鼠肠道CB1受体mRNA表达上调(P<0.05),结肠FAAH和MAGLmRNA和蛋白表达显著下调(P<0.05)。结论:REM睡眠剥夺降低大鼠内脏感觉的作用与外周内源性大麻素代谢降低有关。展开更多
目的:探讨慢性心衰大鼠室旁核(PVN)内脂肪酸酰胺水解酶(FAAH)表达失衡导致中枢交感传出增加的机制。方法:雄性Wistar大鼠左冠状动脉结扎8周后,用超声心动图检测心功能,并通过组织病理学测定心肌梗死面积,鉴定大鼠心衰模型构建成功;酶联...目的:探讨慢性心衰大鼠室旁核(PVN)内脂肪酸酰胺水解酶(FAAH)表达失衡导致中枢交感传出增加的机制。方法:雄性Wistar大鼠左冠状动脉结扎8周后,用超声心动图检测心功能,并通过组织病理学测定心肌梗死面积,鉴定大鼠心衰模型构建成功;酶联免疫吸附法测血浆去甲肾上腺素(NE)水平;Western blot测定PVN内FAAH蛋白表达量;高效液相色谱法测定PVN内N-花生四烯酰乙醇胺(AEA)的生成量;PVN微量注射AEA、FAAH抑制剂PF3845或r AAV2-FAAH sh RNA病毒,记录交感驱动和心功能指标的变化。结果:与假手术组相比,心衰组心功能显著降低,血浆NE显著增加,PVN内FAAH表达量显著上调,AEA生成量显著减少(P<0.05);PVN微量灌注PF3845、AEA或r AAV2-FAAH sh RNA病毒后,心衰组交感驱动指标显著降低,心功能明显改善。结论:心衰状态下PVN内FAAH蛋白表达上调可能引起AEA生成量的减少,从而增强交感神经兴奋性,恶化心衰。展开更多
Morinda citrifolia (noni) fruit juice has been shown to have a wide variety of potential health benefits in human clinical trials. It may also influence the endocannabinoid system of the body. Since the main ingredien...Morinda citrifolia (noni) fruit juice has been shown to have a wide variety of potential health benefits in human clinical trials. It may also influence the endocannabinoid system of the body. Since the main ingredient of the product studied in these clinical trials was juice made from noni fruit puree from French Polynesia, it was evaluated for its ability to inhibit the two major endocannabinoid degradation enzymes in vitro. Noni fruit juice inhibited both fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) in a concentration-dependent manner, suggesting that it may help maintain anandamide and 2-arachidonoylglycerol levels. Samples of the puree were also analyzed for the presence of characteristic phytochemical markers of authentic noni fruit such as scopoletin, rutin, quercetin, deacetylasperulosidic acid and asperulosidic acid, all of which were present. Also present was scandoside, which is reported for the first time as being identified in noni fruit or its juice. Some of these compounds may contribute to the FAAH and MAGL inhibiting activity of noni juice. These results reveal another set of mechanisms by which noni juice possibly supports mental health, maintains joint health, relieves discomfort and modulates the immune system.展开更多
文摘Morinda citrifolia (noni) fruit juice has exhibited a variety of biological activities in human clinical trials, indicating that it influences multiple systems of the body. Since the 1990s, the endocannabinoid system (ECS) has been found to modulate the activity of other organ systems. To investigate noni’s potential impact on the ECS, extracts from freeze-dried noni fruit were evaluated in fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) inhibition assays. The ethyl acetate extract demonstrated the greatest activity against both enzymes. Lignans in this extract also inhibited enzyme activities, with americanin A being the most active in both assays. Americanoic acid and 3,3’-bisdemethylpinoresinol were the next most active compounds. These results suggest that lignans in noni fruit may influence endocannabinoid levels within the body via FAAH and MAGL inhibition. This reveals another set of probable mechanisms of action by which noni juice affects human health.
文摘Background:The expression,localization,and function of the endocannabinoid system has been well characterized in recent years in the monkey retina and in the primary thalamic relay,the lateral geniculate nucleus(dLGN).Few data are available on cortical recipients’structures of the dLGN,namely the primary visual cortex(V1).The goal of this study is to characterize the expression and localization of the metabotropic cannabinoid receptor type 1(CB1R),the synthesizing enzyme N-acyl phosphatidyl-ethanolamine phospholipase D(NAPE-PLD),and the degradation enzyme fatty acid amide hydrolase(FAAH)in the vervet monkey area V1.Methods:Using Western blots and immunohistochemistry,we investigated the expression patterns of CB1R,NAPE-PLD,and FAAH in the vervet monkey primary visual cortex.Results:CB1R,NAPE-PLD,and FAAH were expressed in the primary visual cortex throughout the rostro-caudal axis.CB1R showed very low levels of staining in cortical layer 4,with higher expressions in all other cortical layers,especially layer 1.NAPE-PLD and FAAH expressions were highest in layers 1,2 and 3,and lowest in layer 4.Conclusions:Interestingly enough,CB1R was very low in layer 4 of V1 in comparison to the other cortical layers.The visual information coming from the dLGN and entering layer 4Calpha(magno cells)and 4Cbeta(parvo cells)may be therefore modulated by the higher expression levels of CB1R in cortical layers 2 and 3 on the way to the dorsal and ventral visual streams.This is further supported by the higher expression of NAPE-PLD and FAAH in the outer cortical layers.These data indicate that CB1R system can influence the network of activity patterns in the visual stream after the visual information has reached area V1.These novel results provide insights for understanding the role of the endocannabinoids in the modulation of cortical visual inputs,and hence,visual perception.
文摘Background:The goal of this study is to determine the expression and localization of the cannabinoid receptor type 1(CB1R),the synthesizing enzyme N-acyl phosphatidyl-ethanolamine phospholipase D(NAPE-PLD),and the degradation enzyme fatty acid amide hydrolase(FAAH)in the vervet monkey area V1 to better understand the mechanisms underlying the effects of eCB system modulation on cortical visual processing.Methods:Using Western blots and immunohistochemistry,we investigated the laminar and cellular expression patterns of CB1R,NAPE-PLD,and FAAH across the rostrocaudal axis of the vervet monkey(Chlorocebus sabaeus)primary visual cortex.Results:CB1R,NAPE-PLD,and FAAH were expressed in V1 throughout the rostrocaudal axis.CB1R showed very low staining in layer(L)4,with higher expression in all other layers,especially L1,followed by L2 and L3.NAPE-PLD and FAAH expression patterns were similar,but not quite as low in L4.CB1R,NAPE-PLD,and FAAH were localized in vGlut2-positive cells,representing glutamatergic projection neurons,and in somatostatin(SST)-positive cells,a class of GABAergic interneurons.Conclusions:The low level of CB1R in L4 indicates less direct endocannabinoid modulation of V1 afferents from the dLGN,but that greater modulation may occur via the higher expression of CB1R in L2 and L3 on the way to the dorsal and ventral visual streams.This is further supported by the higher expression of NAPE-PLD and FAAH in these layers.Expression in vGlut2-positive and SST-positive cells represents a role at both glutamatergic and GABAergic neurons.These data indicate that CB1R may influence the network of activity patterns in the visual streams after the visual information has reached V1,and thus may influence visual perception.
基金supported by the National Natural Science Foundation of China(20773089)Scientific Research Foundation for the Returned Overseas Chinese Scholars,Ministry of Education,China(20071108-18-15)~~
文摘背景:内脏感觉过敏是功能性胃肠病的重要病理生理机制之一,快眼动(REM)睡眠剥夺可降低大鼠内脏感觉,但具体机制尚不明。目的:研究外周内源性大麻素系统在REM睡眠剥夺所致大鼠内脏感觉降低中的作用。方法:24只雄性Sprague-Dawley大鼠随机分为实验对照组、睡眠剥夺组和利莫那班干预组。采用花瓶技术制作REM睡眠剥夺大鼠模型。睡眠剥夺48 h后行结直肠扩张(CRD),记录腹壁肌电图,以反映内脏感觉功能的变化。采用逆转录聚合酶链反应(RT-PCR)和蛋白质印迹法分别测定大鼠肠道组织中1型大麻素(CB1)受体、脂肪酰胺水解酶(FAAH)和单酰基甘油脂酶(MAGL)mRNA和蛋白表达。结果:予不同扩张压力(40、60和80 mm Hg)后,睡眠剥夺组大鼠腹外斜肌放电次数显著低于实验对照组(P<0.05);利莫那班干预组放电次数显著高于睡眠剥夺组(P<0.05),但与实验对照组无明显差异。与实验对照组相比,睡眠剥夺组大鼠肠道CB1受体mRNA表达上调(P<0.05),结肠FAAH和MAGLmRNA和蛋白表达显著下调(P<0.05)。结论:REM睡眠剥夺降低大鼠内脏感觉的作用与外周内源性大麻素代谢降低有关。
文摘目的:探讨慢性心衰大鼠室旁核(PVN)内脂肪酸酰胺水解酶(FAAH)表达失衡导致中枢交感传出增加的机制。方法:雄性Wistar大鼠左冠状动脉结扎8周后,用超声心动图检测心功能,并通过组织病理学测定心肌梗死面积,鉴定大鼠心衰模型构建成功;酶联免疫吸附法测血浆去甲肾上腺素(NE)水平;Western blot测定PVN内FAAH蛋白表达量;高效液相色谱法测定PVN内N-花生四烯酰乙醇胺(AEA)的生成量;PVN微量注射AEA、FAAH抑制剂PF3845或r AAV2-FAAH sh RNA病毒,记录交感驱动和心功能指标的变化。结果:与假手术组相比,心衰组心功能显著降低,血浆NE显著增加,PVN内FAAH表达量显著上调,AEA生成量显著减少(P<0.05);PVN微量灌注PF3845、AEA或r AAV2-FAAH sh RNA病毒后,心衰组交感驱动指标显著降低,心功能明显改善。结论:心衰状态下PVN内FAAH蛋白表达上调可能引起AEA生成量的减少,从而增强交感神经兴奋性,恶化心衰。
文摘Morinda citrifolia (noni) fruit juice has been shown to have a wide variety of potential health benefits in human clinical trials. It may also influence the endocannabinoid system of the body. Since the main ingredient of the product studied in these clinical trials was juice made from noni fruit puree from French Polynesia, it was evaluated for its ability to inhibit the two major endocannabinoid degradation enzymes in vitro. Noni fruit juice inhibited both fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) in a concentration-dependent manner, suggesting that it may help maintain anandamide and 2-arachidonoylglycerol levels. Samples of the puree were also analyzed for the presence of characteristic phytochemical markers of authentic noni fruit such as scopoletin, rutin, quercetin, deacetylasperulosidic acid and asperulosidic acid, all of which were present. Also present was scandoside, which is reported for the first time as being identified in noni fruit or its juice. Some of these compounds may contribute to the FAAH and MAGL inhibiting activity of noni juice. These results reveal another set of mechanisms by which noni juice possibly supports mental health, maintains joint health, relieves discomfort and modulates the immune system.
