Neuroprotective effects of Longxue Tongluo Capsule on ischemic stroke rats revealed by LC-MS/MS-based metabolomics approach

Objective: The present study aimed to evaluate the therapeutic effect and explore the underlying mechanisms of Longxue Tongluo Capsule (LTC) on ischemic stroke rats. Methods: Twenty-six rats were randomly divided into four groups, including sham group, sham + LTC group, MCAO group, and MCAO + LTC group. Ischemic stroke rats were simulated by middle cerebral artery occlusion (MCAO), and LTC treatment group were orally administrated with 300 mg/kg of LTC once daily for seven consecutive days. LTC therapy was validated in terms of neurobehavioral abnormality evaluation, cerebral infarct area, and histological assessments. The plasma metabolome comparisons amongst different groups were conducted by UHPLC-Q Exactive MS in combination with subsequent multivariate statistical analysis, aiming to finding the molecules in respond to the surgery or LTC treatment. Results: Intragastric administration of LTC significantly decreased not only the neurobehavioral abnormality scores but also the cerebral infarct area of MCAO rats. The interstitial edema, atrophy, and pyknosis of glial and neuronal cells occurred in the infarcted area, core area, and marginal area of cerebral cortex were improved after LTC treatment. A total of 13 potential biomarkers were observed, and Youden index of 11 biomarkers such as LysoPC, SM, and PE were more than 0.7, which were involved in neuroprotective process. The correlation and pathway analysis showed that LTC was beneficial to ischemic stroke rats via regulating glycerophospholipid and sphingolipid metabolism, together with nicotinate and nicotinamide metabolism. Heatmap and ternary analysis indicated the synergistic effect of carbohydrates and lipids may be induced by flavonoid intake from LTC. Conclusion: The present study could provide evidence that metabolomics, as systematic approach, revealed its capacity to evaluate the holistic efficacy of TCM, and investigate the molecular mechanism underlying the clinical treatment of LTC on ischemic stroke.     

基于BDNF/TrkB/p-CREB信号通路探讨血府逐瘀胶囊促进神经再生防治卒中后抑郁的作用及机制

目的 探讨血府逐瘀胶囊对卒中后抑郁（post-stroke depression,PSD）大鼠抑郁症状的改善作用,并基于神经再生关键通路脑源性神经营养因子（brain derived neurotrophic factor,BDNF）/酪氨酸激酶受体B(tyrosine kinase receptor,TrkB)/磷酸化环腺苷酸应答元件结合蛋白（phosphorylated cAMP response element-binding protein,p-CREB）探讨其机制。方法 采用短暂大脑中动脉梗塞（transient middle cerebral artery occlusion,tMCAO）复合慢性不可预知应激（chronic unpredictable mild stimulation,CUMS）方法复制PSD大鼠模型。大鼠随机分为假手术组、模型组及血府逐瘀低、高剂量（0.43、0.86 g/kg）组和氟西汀（1.8 mg/kg）组,每组18只。连续给予药物干预28 d,利用神经功能评分、糖水偏好实验、旷场实验、强迫游泳实验考察血府逐瘀胶囊对PSD大鼠神经功能损伤以及抑郁症...     

痹祺胶囊治疗类风湿性关节炎的药效研究及网络机制预测

目的 基于Ⅱ型胶原诱导的类风湿性关节炎（rheumatoid arthritis,RA）大鼠模型和网络药理学方法探讨痹祺胶囊的药效作用及作用机制。方法 SD大鼠采用Ⅱ型胶原蛋白造模,造模成功大鼠随机分为模型组,痹祺胶囊（0.05、0.10、0.20、0.40 g/kg）组及泼尼松（10 mg/kg）组和雷公藤总苷（10 mg/kg）组,连续给药15 d。持续监测大鼠体质量、足趾肿胀度和关节炎评分,苏木素-伊红染色考察大鼠踝关节病理变化,ELISA法测定血清细胞因子含量,初步评价痹祺胶囊治疗效果。选择痹祺胶囊中39个化合物为研究对象,依据反向药效团匹配方法和TCMSP、Uniprot等数据库预测化合物作用靶点,与通过OMIM、Dis Ge Net等数据库收集的RA相关靶点相互交互,将交互靶点借助Omicsbean、STRING等数据库平台对获得靶点进行基因本体功能和京都基因与基因组百科全书（Kyoto encyclopedia of genes and genomes,KEGG）通路富集分析,利用Cytoscape软件构建“药材-化合物-靶点-通路-功效-疾病”网络,预测其可能的作用机制...     

通脉活血灵胶囊对实验性高脂血症家兔血脂及动脉粥样硬化的影响

观察通脉活血灵胶囊对实验性高脂血症家兔血脂调节变化和动脉粥样经形成的影响。实验结果表明,高脂饲料喂养家兔可导致高脂血症,并可诱发动脉弱样硬化。     

正交试验法优选银翘解毒软胶囊的水煮提取工艺

采用Ｌ９（３＾４）正交设计,以浸膏得率,正丁醇浸出率,绿原酸含量为考察指标,优选银翘解毒软胶囊的水煮提取工艺。结果表明：最佳提取工艺为首次加１０倍量水,浸泡３０ｍｉｎ,煎煮２ｈ,第２次加８倍量水,煎煮１．５ｈ。     

晶珠肝泰舒胶囊治疗肝炎肝硬变60例

观察了服用晶珠肝泰舒胶囊治疗慢性肝炎 ５２例、肝炎后肝硬化（代偿期） ８例。经 ３个月（ １疗程）治疗,全部病例临床症状、体征与肝功改善均较显著,显效率达８３ ３３％。其中对肝炎后肝硬变作用明显,提示晶珠肝泰舒胶囊在保肝同时,还有一定抗肝纤维化作用。对乙肝病毒血清标志物ＨＢＶ－ＤＮＡ阴转率１２ ５％,ＨＢｓＡｇ阴转率１５．７８％,ＨＢｃＡｇ转阴率７ ４％,提示晶珠肝泰舒胶囊具有抗病毒作用。     

益气通络方对大鼠短暂性脑缺血后海马DND的保护作用

目的 :探讨益气通络方对大鼠短暂性脑缺血后海马迟发性神经元死亡 (DND)的保护作用及其机制。方法 :用Pulsinelli四血管闭塞法制作全脑缺血模型。实验动物随机分为假手术对照组、脑缺血加生理盐水组和脑缺血加益气通络方组。缺血再灌 3天后进行HE染色、TUNEL染色。结果 :①HE染色 ,光镜下观察CA1区组织病理学变化 ,并用显微测微尺测量CA1区存活锥体细胞密度 (存活锥体细胞的个数 /mm) ,表明益气通络口服液组 ( 1 1 4 .5± 1 9.0 )与生理盐水组 ( 1 0 .5± 3.0 )比较 ,P <0 .0 1。②TUNEL染色 ,光镜下假手术组未见阳性结果 ,缺血再灌流加生理盐水组CA1区大部分锥体神经元发生凋亡 ( 1 2 4 .0± 1 1 .5) ,益气通络方组CA1区凋亡的锥体神经元明显减少 ( 2 4 .5± 3.0 ) ,存活细胞增多。结论 :益气通络方能够显著降低大鼠短暂性脑缺血后海马迟发性神经元死亡 ,抑制细胞凋亡可能是其临床疗效的机制之一。     

“生精胶囊”对大鼠的生精作用的研究

本文用病理学的计数方法研究了“生精胶囊”对大鼠的生精作用。结果表明“生精胶囊”能明显增加睾丸曲细精管内生殖细胞数目、睾丸内精子数目、曲细精管数量及其直径和曲细精管内细胞层数,增加精子活率而对初级精母细胞直径及精子活动力无明显影响。为临床该药治疗“男性不育少精症”提供了科学依据。     

中药壮骨胶囊治疗Ⅰ型原发性骨质疏松症74例临床研究

目的　探讨中药壮骨胶囊对Ⅰ型原发性骨质疏松症的疗效及其与骨代谢的关系。方法　采用益肾健脾的中药壮骨胶囊治疗７４ 例绝经后妇女原发性骨质疏松症,并与钙尔奇Ｄ 治疗的３１ 例作对照。结果　３ 个月后,其总有效率达９１ ．８９ ％ ,骨质疏松程度、血ＡＬＰ、ＣＴ、Ｅ２ 皆显著改善,且显著优于对照组（ Ｐ＜ ０．０５ ～０．０１）。无明显副反应。结论　绝经后妇女骨质疏松症主要由肾虚所致,采用中药补肾健脾治疗,疗效显著优于补钙、雌激素的替代疗法等。壮骨胶囊有调整骨代谢作用。该药安全可长期服用     

Pharmacokinetic aspects of rectal formulations of Temazepam

An in vitro/in vivo study was carried out with different rectal formulations of temazepam. Pharmacokinetic data were determined in a cross-over study in 10 volunteers after rectal administration of 10 mg temazepam as a polyethylene glycol based suppository (selected from in vitro data), a liquid-filled capsule and a micro-enema respectively, using oral administration of a liquid-filled capsule as a reference. Serum levels of temazepam indicate an instantaneous and complete release from the micro-enema (F_rel=0.94±0.21, C_max 205±36.9 g/l, t_max 0.49±0.31 hour) and a slower but complete release of temazepam from the suppository (F_rel=1.01±0.25, C_max 202±41.3 g/l, t_max 1.48±0.41 hour). A high interindividual variation in absorption profiles was observed after rectal administration of the liquid-filled capsule (F_rel 0.72±0.36, C_max 182±122 g/l, t_max 4.08±4.28 hour), which makes it less suitable for rectal use. The micro-enema and suppository appear to be useful as rectal formulations for temazepam.