基于代谢通路调控的沙棘籽油抗抑郁作用机制研究

目的采用1H-NMR代谢组学技术结合KEGG数据库,分析沙棘籽油干预慢性温和不可预知应激(CUMS)抑郁大鼠血清和尿液中代谢物及其代谢通路的变化,探讨沙棘籽油抗抑郁的作用机制。方法复制CUMS模型,同步给予沙棘籽油干预,连续4周。采集大鼠血清和尿液进行1H-NMR检测,利用代谢组学技术分析血清和尿液中代谢物的变化,搜索KEGG数据库分析代谢通路。结果在血清和尿液中共寻找出17个与抑郁症相关的潜在生物标志物,其中血清中有9个,包括与对照组比较升高的脂质、β-羟基丁酸、乳酸、N-乙酰糖蛋白和降低的丙氨酸、甜菜碱、氧化三甲胺、α-葡萄糖、β-葡萄糖;尿液中有8个,包括与对照组比较升高的琥珀酸酯、天冬氨酸盐和降低的醋酸、2-酮戊二酸、柠檬酸、三甲胺、甜菜碱、苯丙氨酸。沙棘籽油干预后上述差异代谢物均出现了不同程度的回调,接近对照组水平。结论沙棘籽油主要是通过调节体内的能量代谢、脂质代谢、氨基酸代谢、甲胺代谢和神经递质的合成等代谢通路发挥抗抑郁作用。     

人参皂苷对慢性应激抑郁模型大鼠行为学及HPA轴、BDNF的影响

目的:探讨人参皂苷对慢性应激所致大鼠抑郁模型的干预作用.方法:通过测定大鼠血清中皮质酮(COR)、糖皮质激素受体(GR)、盐皮质激素受体(MR)和脑组织中神经营养(BDNF)的mRNA表达水平,探讨人参皂苷的抗抑郁机制.结果:与正常组大鼠比较,经过慢性应激6周后大鼠糖水偏好显著下降,强迫游泳测试不动时间明显增加,表明慢性应激导致大鼠产生抑郁样行为.同时,抑郁大鼠的血清COR水平增加,海马GR、海马及皮层BDNF的mRNA表达水平均明显降低.给予人参皂苷(12.5,25,50 mg·kg-1)6周后,发现其能显著改善由慢性应激所致的大鼠抑郁行为及生化指标.各个组间海马MR的mRNA表达水平没有显著差异.结论:人参皂苷的抗抑郁作用机制可能通过调节下丘脑-垂体-肾上腺轴功能,进而提高脑组织BDNF 表达水平.     

表没食子儿茶素没食子酸酯对慢性温和不可预知应激抑郁小鼠的保护作用

目的研究表没食子儿茶素没食子酸酯(EGCG)的抗抑郁作用。方法制备慢性温和不可预知应激(CUMS)刺激小鼠抑郁模型;通过旷场实验、体质量、糖水偏爱率、强迫游泳实验和悬尾实验静止时间等指标考察EGCG的抗抑郁作用;检测血清皮质酮(CORT)、促肾上腺皮质激素(ACTH)水平;检测海马组织丙二醛(MDA)水平及超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-Px)活性;实时定量PCR(RT-PCR)检测海马组织中吲哚胺2,3-双加氧酶(IDO)、白细胞介素-1β(IL-1β)、IL-6 m RNA表达。结果 EGCG改善小鼠抑郁状态行为活动;降低血清CORT、ACTH水平;减少海马中MDA的量,提高SOD、GSH-Px活性,下调IDO、IL-6及IL-1βm RNA表达。结论 EGCG可改善小鼠抑郁症状,其机制可能与降低血清中CORT、ACTH水平,抑制海马中MDA的生成,促进SOD、GSH-Px分泌,以及下调IDO、IL-6、IL-1β基因表达有关。     

交泰丸对慢性温和不可预知性应激抑郁模型大鼠炎性细胞因子的影响

目的探讨交泰丸对慢性温和不可预知性应激(CUMS)抑郁模型大鼠致炎、抗炎细胞因子的影响。方法大鼠采用CUMS方法制备抑郁模型,比较体质量变化,进行糖水消耗实验和开场实验;并采用酶联免疫吸附测定法(ELISA)测定大鼠血清及海马组织中炎性细胞因子白细胞介素(IL)-1β、IL-6、肿瘤坏死因子(TNF)-α、IL-4、IL-10的水平,尼氏染色法观察大鼠海马神经元形态。结果与对照组比较,模型组大鼠糖水消耗量、穿越横格数和直立次数均明显减少;血清及海马内IL-1β、IL-6、TNF-α、IL-4明显升高,IL-10明显降低;海马神经元分层不清,排列紊乱,尼氏体浅染或消失。与模型组比较,交泰丸给药组大鼠糖水消耗量、穿越横格数和直立次数均明显增加;血清及海马内IL-1β、IL-6、TNF-α明显降低,IL-4、IL-10明显升高;海马神经元分层较明显,尼氏体浅染。结论交泰丸可明显改善大鼠抑郁样行为及海马神经元损伤,其机制可能与下调血清及海马致炎细胞因子IL-1β、IL-6、TNF-α和上调抗炎细胞因子IL-4、IL-10表达有关。     

Effects of Marapuama in the chronic mild stress model: further indication of antidepressant properties

ETHNOPHARMACOLOGY RELEVANCE: Ptychopetalum olacoides Bentham (PO) (Olacaceae), known as Marapuama, is regarded as a "nerve tonic" in the Amazon. Traditional uses include states of lassitude with noticeable lack of desire/motivation, and to manage particularly stressful (physical and/or psychological) circumstances. Suggestive of antidepressant activity, we have established that a specific PO ethanol extract (POEE) significantly decreases immobility in the tail suspension and forced swimming tests. AIM OF THE STUDY: The aim of this study was to verify the effects of POEE in the unpredictable chronic mild stress (UCMS) depression model in mice, given the construct and face values of the UCMS as an experimental model of depression and the traditional use of this species. MATERIALS AND METHODS: Over 6 weeks BALB/c mice were subjected to the UCMS protocol. The effects of POEE (50, 100, 300mg/kg, p.o.) and imipramine (20mg/kg, i.p.) were evaluated in relation to coat state, splash-test grooming, and corticosterone levels. RESULTS: The coat state degradation, decreased grooming and increased serum corticosterone induced by UCMS were prevented by POEE and imipramine treatments. CONCLUSION: In addition to supporting traditional claims and previously reported antidepressant properties for POEE, this study shows that POEE prevents stress-induced HPA hyperactivity.     

Essential oil of Perilla frutescens-induced change in hippocampal expression of brain-derived neurotrophic factor in chronic unpredictable mild stress in mice

Ethnopharmacological relevance

Perilla frutescens (Perilla leaf), a traditional Chinese medicinal herb, has been used for centuries to treat various conditions including depression. A previous study of the authors demonstrated that essential oil of Perilla frutescens (EOPF) attenuated the depressive-like behavior in mice.

Aim of the study

This study was undertaken to explore the dynamic change of behaviors and brain-derived neurotrophic factor (BDNF) expression induced by chronic unpredictable mild stress (CUMS), and improved by EOPF.

Materials and methods

Four separate CUMS experimental groups (1-week, 2-week, 3-week and 4-week treatment) were treated with EOPF (3 mg/kg and 6 mg/kg, p.o.) or fluoxetine (20 mg/kg, p.o.), followed by sucrose preference, locomotor activity, immobility and hippocampal BDNF measurement.

Results

EOPF, as well as fluoxetine, restored the CUMS-induced decreased sucrose preference and increased immobility time, without affecting body weight gain and locomotor activity. Furthermore, CUMS (3 or 4-week) produced a reduction in both BDNF mRNA and protein expression in the hippocampus, which were ameliorated by EOPF (4-week) and fluoxetine (3 or 4-week) treatment.

Conclusion

These results presented here show that BDNF is expressed depending on length of CUMS procedure and EOPF administration. And this study might contribute to the underlying reason for the slow onset of antidepressant activity in clinic.     

Antidepressant-like effect of magnolol on BDNF up-regulation and serotonergic system activity in unpredictable chronic mild stress treated rats

Magnolol is the main constituent identified in the barks of Magnolia officinalis, which has been used for the treatment of mental disorders including depression in China. In this study, we investigated the antidepressant‐like effect of magnolol, and its possible mechanisms in rats subjected to unpredictable chronic mild stress (UCMS). High performance liquid chromatography with electrochemical detection (HPLC‐ECD) and immunohistochemical staining analysis were applied to explore the mechanisms underlying the antidepressant‐like effect of magnolol. Magnolol (20, 40 mg/kg) significantly reversed UCMS‐induced reduction in sucrose consumption and deficiency in locomotor activity. In addition, it was observed that administration of magnolol (20, 40 mg/kg) restored brain‐derived neurotrophic factor (BDNF) expression, and normalized the serotonergic system changes in the UCMS‐treated rats. These results confirmed the antidepressant‐like effect of magnolol, which might be based primarily on its ability to increase the BDNF expression and enhance the activity of the serotonergic system in rat brains. Copyright © 2012 John Wiley & Sons, Ltd.     

氟西汀对小鼠慢性不可预知温和应激所致学习记忆减退的改善作用

目的探讨抗抑郁药氟西汀对小鼠慢性不可预知温和应激所致的学习、记忆能力减退的影响。方法将30只健康雄性昆明种小鼠随机分为正常组、模型组、氟西汀组,每组10只。模型组、氟西汀组均给予慢性不可预知温和应激刺激,11种应激因子随机给予,共6周。在刺激过程中,氟西汀组每天给予氟西汀20 mg/kg灌胃,模型组给予同等体积的双蒸水灌胃。刺激结束后,应用水迷宫实验方法评价小鼠学习、记忆能力。结果刺激6周后,模型组小鼠空间学习、记忆能力均显著低于正常组(P均<0.05),氟西汀组学习、记忆能力均较模型组明显改善(P均<0.05)。结论氟西汀对慢性不可预知温和应激所致学习、记忆能力损伤具有明显改善作用。     

基于NO-cGMP信号转导通路交泰丸对慢性温和不可预知性应激抑郁大鼠的抗抑郁作用研究

目的基于一氧化氮-环磷酸鸟苷酸(NO-cGMP)信号转导通路探讨交泰丸对慢性温和不可预知性应激(CUMS)抑郁模型大鼠的抗抑郁作用。方法采用CUMS进行大鼠抑郁模型造模,实验第21天各给药组连续ig治疗药物14 d。采用ELISA法检测大鼠海马组织及血浆中NO和cGMP水平;RT-PCR法检测大鼠海马组织中一氧化氮合酶(包括iNOS、nNOS)及NMDA受体亚单位NR1、NR2A和NR2B基因mRNA表达。结果与对照组比较,模型组大鼠海马组织及血浆中NO、cGMP水平明显升高;大鼠海马组织中iNOS mRNA、nNOS mRNA、NR1 mRNA、NR2A mRNA、NR2B mRNA表达显著升高。与模型组相比,交泰丸高、中、低剂量(3.00、1.50、0.75 g/kg)及阳性药盐酸氟西汀均可逆转以上指标的改变。结论交泰丸可通过调节NO-cGMP信号转导通路达到抗抑郁作用。     

基于慢性温和不可预知应激模型内源性代谢物变化探讨抑郁症病理机制

代谢组学是对某一生物或细胞所有低相对分子质量代谢产物进行定性和定量分析的一门新学科,由于其应用前景广泛,目前已成为系统生物学的重要组成部分.采用代谢组学技术发现慢性温和不可预知应激(CUMS)模型诱导的抑郁症病理机制与多种内源性代谢物有关,按化学类别该内源性代谢物可以分为氨基酸、脂肪酸、糖类、核苷酸、脂蛋白、N-乙酰糖蛋白、苯丙乙酰甘氨酸、胆碱、胆酸、溶血磷脂酰胆碱等物质;按代谢途径可以分为氨基酸代谢、能量代谢、肠微生物代谢、酮体代谢等途径.抑郁症病理机制不是某个代谢途径异常或某个特定区域单独受到扰动的结果,而是多个代谢途径异常或者多个区域的联合效应.对基于代谢组学技术分析CUMS诱导的抑郁症发病机制的研究进展进行综述.     

Effects of peony glycosides on mice exposed to chronic unpredictable stress: Further evidence for antidepressant-like activity

Ethnopharmacology relevance

Peony, the processed root of Paeonia lactiflora Pall. (Ranunculaceae), is a component herb of many traditional formulae for the treatment of depression-like disorders.

Aim of the study

The present study aimed to investigate whether the total glycosides of peony (TGP) could prevent depression induced by chronic stress.

Materials and methods

Mice were subjected to an experimental setting of chronic unpredictable stress (CUS). The effect of TGP treatment on CUS-induced depression was examined by measuring behavioral and neurochemical parameters of depression and the antioxidant status of brain tissue.

Results

CUS-induced depression, as indicated by a significant increase in immobility time in the tail suspension test, was associated with increases in the activities of monoamine oxidases, depletion of reduced glutathione, and an increase in malondialdehyde level, in mice brains. TGP treatment alleviated the extent of CUS-induced depression and the associated impairment of antioxidant status in the mouse brain.

Conclusion

The results suggest that TGP alleviates depression induced by chronic unpredictable stress. The antidepressant-like activity of TGP is probably mediated by inhibition of monoamine oxidases and the attenuation of oxidative stress in mouse brain.     

Antidepressant-like effect of essential oil of Perilla frutescens in a chronic,unpredictable, mild stress-induced depression model mice

Perilla frutescens（Perilla leaf）, a garnishing vegetable in East Asian countries, as well as a plant-based medicine, has been used for centuries to treat various conditions, including depression. Several studies have demonstrated that the essential oil of P. frutescens（EOPF） attenuated the depressive-like behavior in mice. The present study was designed to test the anti-depressant effects of EOPF and the possible mechanisms in an chronic, unpredictable, mild stress（CUMS）-induced mouse model. With the exposure to stressor once daily for five consecutive weeks, EOPF（3, 6, and 9 mg·kg-1） and a positive control drug fluoxetine（20 mg·kg-1） were administered through gastric intubation to mice once daily for three consecutive weeks from the 3rd week. Open-field test, sucrose consumption test, tail suspension test（TST）, and forced swimming test（FST） were used to evaluate the behavioral activity. The contents of 5-hydroxytryptamine（5-HT） and its metabolite, 5-hydroxyindoleacetic acid（5-HIAA）, in mouse hippocampus were determined by HPLC–ECD. Serum interleukin（IL）-1, IL-6, and tumor necrosis factor（TNF）-α levels were evaluated by enzyme-linked immunosorbent assay（ELISA）. The results showed that CUMS significantly decreased the levels of 5-HT and 5-HIAA in the hippocampus, with an increase in plasma IL-6, IL-1β, and TNF-α levels. CUMS also reduced open-field activity, sucrose consumption, as well as increased immobility duration in FST and TST. EOPF administration could effectively reverse the alterations in the concentrations of 5-HT and 5-HIAA; reduce the IL-6, IL-1β, and TNF-α levels. Moreover, EOPF could effectively reverse alterations in immobility duration, sucrose consumption, and open-field activity. However, the effect was not dose-dependent. In conclusion, EOPF administration exhibited significant antidepressant-like effects in mice with CUMS-induced depression. The antidepressant activity of EOPF might be related to the relation between alteration of seroto     

柴胡白芍药对对慢性温和不可预知性应激抑郁模型大鼠行为学的影响

目的 观察柴胡白芍药对对慢性温和不可预知性应激(CUMS)抑郁模型大鼠行为学的影响,验证柴胡白芍药对的抗抑郁作用。方法基于CUMS抑郁大鼠模型观察给予柴胡白芍药对后大鼠的行为学改变,包括大鼠的体质量、糖水消耗情况以及旷场实验活动行为情况。结果给大鼠柴胡白芍药对14 d后,柴胡白芍药对低、中、高各剂量组大鼠的体质量、糖水消耗量以及旷场实验中穿越横格数及直立次数均显著增加。说明柴胡白芍药对可以改善大鼠的抑郁行为。单用柴胡和单用白芍也可以不同程度改善部分指标。结论柴胡白芍药对对大鼠有明显抗抑郁作用。     

去势法联合慢性不可预知性温和应激法建立围绝经期综合征肝郁证动物模型的研究

目的:采用去势法联合慢性不可预知性温和应激法(CUMS)建立围绝经期综合征肝郁证大鼠动物模型.方法:SPF级雌性3月龄SD大鼠30只,按照体质量分层随机分为假手术组、去势组以及模型组,每组10只.假手术组大鼠摘除卵巢旁脂肪组织,去势组及模型组大鼠行去势手术,采用苏木素—伊红染色(HE)观察大鼠阴道脱落细胞涂片,判断是否...     

慢性轻度不可预见性应激对动脉粥样硬化模型大鼠内皮功能的影响

目的:探讨慢性轻度不可预见性应激对高脂诱导动脉粥样硬化模型大鼠内皮功能的影响。方法:雄性大鼠分为空白对照组、应激组、高脂组、应激+高脂组。高脂组给予高脂饲料,应激组给予慢性轻度不可预见性应激。10周后取主动脉弓,做HE染色,并测定血清中血脂、皮质醇(CORT)、一氧化氮(NO)、内皮素-1(ET-1)水平。结果:高脂组与应激+高脂组均可引起大鼠主动脉弓发生AS病变,其中应激+高脂组的病变程度明显强于高脂组;高脂组与应激+高脂组的血清CHO、LDL-C、HDL-C值均高于空白对照组(P<0.05),其中应激+高脂组的CHO、LDL-C、HDL-C值高于高脂组(P<0.01);高脂组与应激+高脂组血清NO和ET-1的含量也明显高于空白对照组(P<0.01),同时应激+高脂组的血清中NO和ET-1的含量高于高脂组(P<0.05);其他三组的皮质醇浓度都比空白对照组低,与其比较都具有统计学意义。结论:慢性应激能够从影响内皮功能上,促进大鼠动脉粥样硬化的发展进程。     

米邦塔仙人掌果胶对慢性不可预知温和应激小鼠绝望症状的改善作用

目的研究米邦塔仙人掌果胶(MCP)对慢性不可预知温和应激(CUMS)小鼠绝望症状的改善作用。方法雄性昆明种小鼠随机分为空白对照组、模型组、MCP低剂量组(50 mg/kg)、MCP中剂量组(100 mg/kg)、MCP高剂量组(200 mg/kg)。除空白对照组不进行任何应激处理外,其余组均进行CUMS,各MCP组均在进行CUMS期间每天灌胃相应剂量MCP。造模结束24 h后进行悬尾实验,48 h后进行强迫游泳实验。结果模型组悬尾实验潜伏期显著短于空白对照组(P0.01),累计不动时间显著长于空白对照组(P0.01);MCP高剂量组潜伏期显著长于模型组(P0.05),MCP中、高剂量组累计不动时间显著短于模型组(P均0.01)。模型组强迫游泳实验潜伏期显著短于空白对照组(P0.01),累计不动时间显著长于空白对照组(P0.01);MCP各给药组潜伏期与空白对照组比较差异均无统计学意义(P均0.05),而MCP高剂量组累计不动时间显著短于模型组(P0.05)。结论 MCP能较好地缓解CMS小鼠的行为绝望症状。     

慢性温和不可预知应激抑郁模型大鼠粪便1H-NMR代谢组学研究

目的 采用¹H-NMR代谢组学技术研究慢性温和不可预知应激（CUMS）抑郁模型大鼠粪便中内源性代谢产物的变化规律,寻找潜在的生物标志物。方法 大鼠分成模型组与对照组。采用CUMS程序对模型组大鼠进行为期4周的造模,造模结束后收集大鼠粪便。应用¹H-NMR技术及多元统计分析方法分析大鼠粪便提取物中内源性代谢产物的变化规律。结果 模型组与对照组大鼠的行为学指标差别明显,表明CUMS大鼠抑郁模型复制成功。在大鼠粪便的¹H-NMR图谱中可以指认出30种内源性代谢产物,模型组中谷氨酰胺、乳酸、天冬氨酸的量明显增加,而尿嘧啶、酪氨酸、苯丙氨酸的量明显降低,且与对照组相比差异显著（P＜0.05、0.01）。结论 通过研究CUMS抑郁模型大鼠粪便中内源性代谢产物的变化规律,阐明与抑郁症有关的潜在生物标志物,为抑郁症的发病机制及临床诊断研究提供实验依据。     

舒郁抑斑方对慢性心理应激促发动脉粥样硬化大鼠的保护作用

舒郁抑斑方(SYYB)对伴有慢性心理应激的冠心病患者有较好的治疗作用。为观察SYYB对慢性心理应激促发大鼠动脉粥样硬化(athero-sclerosis,As)早期病变形成及其炎症反应的影响,采用高脂饵食+维生素D3(VD3)腹腔注射建立大鼠As早期病变模型(As),在此基础上采用不可预知慢性应激刺激法(As+CUMS),观察慢性心理应激是否加重大鼠病变及SYYB(6.6,13.2,26.4 mg·kg~(-1))的干预作用。采用悬尾实验和新奇实验法观察大鼠行为学改变,检测血清应激激素促肾上腺素(adrenocortico-tropic hormone,ACTH)、皮质醇(cortisol,Cor)、去甲肾上腺素(noradrenaline,NE)的含量,称量胸腺、肾上腺的质量,综合评价SYYB对模型大鼠心理应激的影响。取主动脉弓HE染色观察血管组织病理改变,测定血清甘油三酯(triglycerides,TG)、总胆固醇(total cholesterol,TC)、高密度脂蛋白(HDL-C),评价SYYB对大鼠As病变的影响。检测血清高敏C反应蛋白(high-sensitivity C-reactive protein,hs CRP)、白细胞介素-1β(interleukin-1β,IL-1β)、白细胞介素-6(interleukin-6,IL-6),评价SYYB对As大鼠炎症反应的影响。实验结果显示,与空白组相比,As组TC,TG含量增高,HDL-C明显降低,HE染色可见主动脉壁增厚。As+CUMS组TC,TG含量显著增高,HDL-C明显降低,HE染色可见主动脉弓内膜增厚,泡沫细胞形成,行为学评价及血清应激激素检测结果显示动物存在慢性应激反应,该实验As+CUMS模型复制成功。SYYB可降低血清中TC,TG含量,减轻主动脉泡沫细胞、钙化灶及炎性细胞浸润,对血清中ACTH和Cor,NE有明显的降低作用,同时有效降低了血清中动脉粥样硬化相关的炎性标志物hs-CRP,IL-1和IL-6。提示SYYB对心理应激促发As大鼠的保护作用,其作用与改善神经-内分泌网络平衡及调节相关炎症反应有关。     

Rehmannia glutinosa: review of botany, chemistry and pharmacology

Rehmannia glutinosa, a widely used traditional Chinese herb, belongs to the family of Scrophulariaceae, and is taken to nourish Yin and invigorate the kidney in traditional Chinese medicine (TCM) and has a very high medicinal value. In recent decades, a great number of chemical and pharmacological studies have been done on Rehmannia glutinosa. More than 70 compounds including iridoids, saccharides, amino acid, inorganic ions, as well as other trace elements have been found in the herb. Studies show that Rehmannia glutinosa and its active principles possess wide pharmacological actions on the blood system, immune system, endocrine system, cardiovascular system and the nervous system. Currently, the effective monomeric compounds or active parts have been screened for the pharmacological activity of Rehmannia glutinosa and the highest quality scientific data is delivered to support the further application and exploitation for new drug development.     

加味四逆散对慢性轻度不可预计性心理应激模型大鼠神经内分泌免疫网络调控作用的研究

目的:观察慢性心理应激对模型大鼠神经内分泌免疫(NIM)网络的影响以及加味四逆散的调治作用。方法:大鼠随机分为6组:雌性正常组,雌性模型组,雌性加味四逆散组,雄性正常组,雄性模型组,雄性加味四逆散组。建立慢性轻度不可预计性心理应激模型,采用放射免疫方法检测大鼠下丘脑促肾上腺皮质激素释放激素(CRH)、血清肾上腺酮(CORT)和促肾上腺皮质激素(ACTH)含量,观察肾上腺/胸腺器官形态学改变,流式细胞仪计数外周血T淋巴细胞CD3+、CD4+、CD8+。结果:慢性心理应激大鼠下丘脑—垂体—肾上腺皮质(HPA)轴功能亢进,免疫功能受到抑制。加味四逆散可调节慢性心理应激大鼠HPA轴的兴奋性,改善慢性心理应激大鼠免疫功能改变。结论:慢性轻度不可预计性心理应激模型大鼠NIM网络功能发生异常改变,而加味四逆散对其具有一定的调治作用。