基于核磁共振的益母草碱抗急性心肌缺血的代谢组学研究

目的应用核磁共振(NMR)代谢组学技术研究急性心肌缺血以及益母草碱给药大鼠血浆中代谢物组的变化,探讨益母草碱抗心肌缺血作用的机制。方法应用1H NMR分析假手术组、模型组、益母草碱给药组大鼠血浆代谢物组,应用模式识别多变量统计方法研究模型组与假手术组及给药组之间的代谢物组差异。结果正交偏最小二乘法-判别分析(OPLS-DA)结果显示,模型组与假手术组相比有6个代谢物(丙氨酸、赖氨酸、甘氨酸、肌酸、N-乙酰化及O-乙酰化糖蛋白)水平明显增加,而益母草碱干预治疗能明显降低模型组丙氨酸、赖氨酸、甘氨酸水平,并增加胆碱、磷酸胆碱、鲨肌醇含量。结论益母草碱能通过纠正急性心肌缺血氨基酸代谢紊乱,上调胆碱以及肌醇代谢通路发挥心肌保护作用。该研究为评价益母草碱抗心肌缺血作用提供了有力分析手段,并为研究其作用机制提供新的思路。     

黄芪甲苷的药理作用及其机制的研究进展

黄芪甲苷是黄芪的主要有效成分,随着对黄芪甲苷药理作用的深入研究发现,其具有调节免疫、缺血保护、心脏保护、抗炎、抗病毒和抗肿瘤等作用,综述黄芪甲苷药理作用的研究进展,并对其作用机制进行探讨,为进一步研究开发黄芪甲苷提供理论依据。     

益母草总生物碱抗炎镇痛作用的研究

目的:探讨益母草总生物碱的药理作用,从抗炎、镇痛两方面阐明其作用机制。方法:通过观察益母草总生物碱对小鼠腹腔毛细血管通透性的影响,了解其抗炎作用;通过观察益母草总生物碱对醋酸所致小鼠疼痛的影响,了解其镇痛作用;结果:益母草总生物碱具有明显的抗炎镇痛作用。     

小檗碱药理作用及其临床应用研究进展

小檗碱是从传统中药黄连和黄柏中提取出的一种异喹啉类生物碱,在我国拥有悠久的药用历史。小檗碱具有多种药理作用,包括抗病原微生物、抗炎、抗肿瘤、心脏保护、降血糖、调节脂质代谢以及免疫抑制等。多年以来,小檗碱用于肠道感染性疾病的治疗取得显著疗效。近年来,随着研究的不断进展,其临床应用潜力不断被开发,对心血管系统疾病、代谢综合征及其并发症、肿瘤、腹腔黏连和沙眼衣原体感染等均具有较好的效果。本文针对小檗碱多方面的药理作用、分子机制及临床应用现状进行梳理总结,为小檗碱的临床应用和推广提供参考。     

小檗碱抗肝癌药理作用及其机制的研究进展

小檗碱是一种具有广泛药理作用的生物活性物质,除了抗炎、抗菌、抗病毒、抗腹泻、抗高血压、抗缺氧、降血糖和降血脂等作用,还具有抗肿瘤作用。近些年,国内外科研团队对小檗碱在抗肝癌领域的作用进行了诸多深入的研究,并发表了很多重要发现。为此,笔者综述了小檗碱对动物体和人肝癌细胞的抗肝癌药理作用及其机制,并对相关研究做了分析。     

小檗碱调脂的研究进展

盐酸小檗碱（berberine）是从黄连中提取的一种天然的异喹啉类生物碱。小檗碱具有多种药理作用,包括抗病原微生物、抗炎、抗肿瘤、心脏保护、降血糖、调节脂质代谢以及免疫抑制等。近10年来,国内外学者对小檗碱调脂机制进行了广泛的研究。从调节血浆脂质合成、促进脂质分解等方面对小檗碱改善血脂机制加以综述,为其进一步开发和研究提供参考。     

五味子乙素器官保护作用的分子机制研究进展

五味子乙素是五味子中主要活性成分之一,具有多种药理作用.长期研究表明五味子乙素具有保护肝脏、肾脏、肺和心脑血管等作用.五味子乙素的多器官保护作用通过不同的途径起效,作用机制包括抗氧化、抗炎、抗纤维化、促进热休克反应、调节脂质代谢、抑制细胞凋亡.就五味子乙素对各器官的保护作用的分子机制进行了总结,为推进其药理研究和分子机...     

麦冬皂苷D的药理作用研究进展

麦冬皂苷D是从中药麦冬中提取出的甾体皂苷类成分,具有抗炎、抗肿瘤、降脂、心肌保护作用、神经保护作用、胃肠道保护、调节骨代谢等广泛的药理作用。该文对近些年麦冬皂苷D的药理作用研究进行了综述和分析,为其进一步开发提供参考。     

红景天苷对肾脏保护作用的药理机制研究进展

药理学研究已经证实红景天苷具有抗炎、抗肿瘤、免疫调节、促进骨和骨骼肌生长、抗氧化、增体质以及抗疲劳、抗肌萎缩、抗骨质疏松、抗痴呆和保护肝脏、神经、肺、呼吸道、心脏、血管的作用,以及具有降血糖、调血脂、抗肥胖等药理作用。综述红景天苷保护肾脏作用的研究资料,并认为红景天苷极有可能被开发成防治代谢综合征、心脑血管病及其并发症药物,并对其药理机制研究进展做了分析。     

甲基莲心碱治疗心血管疾病的药理作用及其机制研究进展

甲基莲心碱是从睡莲科植物莲Nelumbo nucifera成熟种子的胚芽中提取出的一种双苄基异喹啉类生物碱,具有抗动脉粥样硬化、抗高血压、抗血栓、抗糖尿病血管病变和血管保护作用、抗心律失常等作用。心血管疾病是全球发病率和死亡率最高的一类疾病,包括心绞痛、高血压、高血脂、动脉粥样硬化。近年来,有研究表明甲基莲心碱对心血管疾病防治具有疗效好、副作用低的特点。对甲基莲心碱在心血管疾病中的药理作用及其机制进行综述,为甲基莲心碱的药物研发和临床应用提供参考。     

PROTECTIVE EFFECTS OF LEONURINE IN NEONATAL RAT HYPOXIC CARDIOMYOCYTES AND RAT INFARCTED HEART

• 1 Previous studies have shown that extracts of Herba leonuri, predominantly containing the phytochemical components leonurine and stachydrine, provide protective effects in the ischaemic myocardium by acting as free radical scavengers and inhibiting the formation of reactive oxygen species.
• 2 The present study was designed to investigate the cardioprotective effects of 10^?6 mol/L leonurine on neonatal rat cardiomyocytes treated with hypoxia plus serum deprivation, a component of ischaemia, and to determine the mechanisms underlying the protective effects with regard to cardiac anti‐oxidant enzymes and apoptosis genes. Cardiomyocytes were treated with leonurine 8 h prior to exposure to hypoxia. In addition, we investigated the effects of 7.5 and 15 mg/kg leonurine, administered to rats i.p. for 7 days prior to left coronary artery ligation, on subsequent infarct size of the ischaemic heart.
• 3 Leonurine significantly increased the viability of cardiomyocytes injured by hypoxia. In the leonurine‐treated group, gene expression levels of pro‐apoptotic genes, namely Bax and Fas, were significantly downregulated (by 0.95‐ and 0.72‐fold, respectively; P < 0.001) compared with the hypoxic control group, whereas the expression of Bcl‐2 and Bcl‐xl was upregulated following leonurine treatment (by 1.03‐ and 1.07‐fold, respectively; P < 0.05). Correspondingly, leonurine treatment increased Bcl‐2 protein levels and decreased Bax protein levels. Assays investigating cardiac anti‐oxidant enzymes provided further evidence for a protective effect of leonurine, as indicated by the induction of the anti‐oxidant enzymes superoxide dismutase and catalase. Furthermore, leonurine decreased infarct size in ischaemic rat heart.
• 4 The results of the present study suggest that the mechanisms of action of leonurine in hypoxic neonatal rat cardiomyocytes and infarcted rat heart may be related to its anti‐oxidant and anti‐apoptotic properties.

     

Molecular basis for the regenerative properties of a secretion of the mollusk Cryptomphalus aspersa

A screen for natural products bearing pharmacological properties has yielded a secretion of the mollusk Cryptomphalus aspersa (SCA), which possesses skin-regenerative properties. In this report, we outline some of the cellular and molecular effects underlying this observation. First, we found that SCA contained antioxidant SOD and GST activities. In addition, SCA stimulated fibroblast proliferation and rearrangement of the actin cytoskeleton. Additional mechanisms involved in the regenerative effect of SCA included the stimulation of extracellular matrix assembly and the regulation of metalloproteinase activities. Together, these effects provide an array of molecular mechanisms underlying SCA-induced cellular regeneration and postulate its use in regeneration of wounded tissue.     

Nicotine,body weight and potential implications in the treatment of obesity

Obesity is an epidemic problem in the U. S. and many other industrialized nations. Historically, the drugs used for the treatment of obesity generally targeted small molecule neurotransmitters. As research grows to decipher the underlying molecular mechanisms behind energy homeostasis, it is becoming evident that the modulating effects of neuropeptides also are critical in the regulation of appetite and metabolism. The search for drugs to modify these monoaminergic and peptidergic pathways may eventually prove successful in the treatment of obesity. While tobacco smoking has long been used as one strategy to maintain a lower body weight, especially in female smokers, its adverse associations with addiction and disease overshadow its potential use as an antiobesity agent. Potential pharmacological effects of nicotine could be better understood as the intricacies of the nicotinic acetylcholine receptor are revealed. The objective of this review is threefold: first is to provide an overview of the physiological effects of nicotine on body weight while focusing on the drugs that are available as antiobesity and smoking cessation agents. Second is to provide the present status of the nicotinic acetylcholine receptor as it relates to energy homeostasis and its potential as an effective treatment modality for obesity. Third is to present the current knowledge with respect to nicotine's effects on energy homeostatic and reward related pathways at the molecular level. A better understanding of the regulatory mechanisms underlying the pharmacological effects of nicotine on body weight will provide insights in identification of potential targets for the development of appropriate medicines in the treatment of obesity.     

Effect of leonurine on the activity of creatine kinase

The effects of leonurine (1) on the activity of creatine kinase (CK) have been studied. The results show that leonurine inhibits enzyme activity in concentration- and time-dependent manners (at 0.75 and 1.51 mmol from 12 to 72 h). There are two mechanisms for the inhibition process. Compound 1 first acts as a non-competitive inhibitor and then as an irreversible inhibitor. Changes of CK were not found in 10% SDS-PAGE, but the amount of dimeric CK decreased in 10% non-SDS gel. The results suggest that 1 can inhibit CK activity by degrading its dimeric structure.     

Neuroprotective effects of leonurine on ischemia/reperfusion-induced mitochondrial dysfunctions in rat cerebral cortex

Ischemic brain is particularly susceptible to free radicals mediated secondary neuronal damage, especially mitochondrial dysfunctions. Chinese Herbal Medicine with antioxidant properties is believed to have potential therapeutic effect. Leonurine, an alkaloid present in Herba Leonuri (HL), has shown biological effects such as antioxidant, anticoagulant, anti-apoptosis and protection against ischemic heart disease. In this study, neuroprotective effects of leonurine against cerebral ischemia/reperfusion-induced mitochondrial dysfunctions in cortex were evaluated. We used transient rat middle cerebral artery occlusion (MCAO) model of brain ischemia. The rats were treated with their respective treatments for 1 week prior to the MCAO. We found that leonurine significantly improved neurological outcome and reduced ischemia/reperfusion (I/R)-induced cerebral infarction 24 h after MCAO. Leonurine decreased reactive oxygen species (ROS) level in mitochondria isolated from ischemic cortex, which was increased by MCAO. Terminal deoxyuridine triphosphate (dUTP) Nick-End Labeling (TUNEL) staining showed anti-apoptotic effect of leonurine on ischemic cortex. Western blot analysis showed a marked decrease in the expression of Bax and an increase of Bcl-2 as a result of leonurine treatment. The attenuation of mitochondrial membrane swelling, restore of mitochondrial membrane potential and content of cytochrome c (Cyt-C) in mitochondria isolated from ischemic cortex could also be observed in leonurine treated group. The findings of this study suggest that leonurine has promising therapeutic effect for ischemic stroke treatment through antioxidant and anti-apoptotic mechanisms.     

Leonurine attenuates lipopolysaccharide-induced inflammatory responses in human endothelial cells: involvement of reactive oxygen species and NF-κB pathways

Leonurine, an active alkaloid of Traditional Chinese Medicine Herba leonuri, displayed cardioprotective effects by anti-oxidative and anti-apoptotic activities in vitro and in vivo. Herein, we explored the effects and possible mechanisms of leonurine on lipopolysaccharide (LPS)-induced inflammatory responses in human umbilical vein endothelial cells (HUVEC). We found that leonurine pretreatment concentration-dependently attenuated LPS-induced mRNA expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E-selectin, and monocyte chemoattractant protein-1. Meanwhile, LPS-mediated expression/release of ICAM-1, VCAM-1, and cyclooxygenase-2, and tumor necrosis factor-α was also reduced by leonurine. In addition, we confirmed that leonurine suppressed degradation of IκBα and phosphorylation of nuclear factor-κB (NF-κB) p65 as well as production of intracellular reactive oxygen species in a concentration dependent manner. Furthermore, the cytoprotective enzyme heme oxygenase-1 could be upregulated in leonurine-treated HUVEC. Our present results indicated leonurine exerted beneficial effects in inflammatory conditions partly through inhibition of reactive oxygen species and NF-κB signaling pathways.     

Progress in pharmacological effects and clinical applications of berberine北大核心CSCD

Berberine is an isoquinoline alkaloid isolated from Rhizoma Coptidis and Cortex Phellodendri, which has a long medical history in China. Recent studies have indicated that berberine has multiple pharmacological activities including anti-inflammatory, anti-microorganisms, anti-cancer, cardiac protection, glucose lowering, regulating lipid metabolism and immune suppression. Berberine has been used for the treatment of intestinal infectious diseases for many years. With the continuous progress of the research, it is reported that berberine has many new clinical applications, including treatment of the cardiovascular disease, metabolic syndrome and its complications, cancers, abdominal adhesions and chlamydia trachomatis infection. This review is intended to introduce the role of berberine in various aspects of pharmacological effects, molecular mechanisms and clinical applications.     

Muscarinic cationic current in gastrointestinal smooth muscles: signal transduction and role in contraction

1 The muscarinic receptor plays a key role in the parasympathetic nervous control of various peripheral tissues including gastrointestinal tract. The neurotransmitter acetylcholine, via activating muscarinic receptors that exist in smooth muscle, produces its contraction. 2 There is the opening of cationic channels as an underlying mechanism. The opening of cationic channels results in influxes of Ca2+ via the channels into the cell and also via voltage-dependent Ca2+ channels which secondarily opened in response to the depolarization, providing an amount of Ca2+ for activation of the contractile proteins. 3 Electrophysiological and pharmacological studies have shown that the cationic channels as well as muscarinic receptors exist in many visceral smooth muscle cells. However, the activation mechanisms of the cationic channels are still unclear. 4 In this article, we summarize the current knowledge of the muscarinic receptor-operated cationic channels, focusing on the receptor subtype, G protein and other signalling molecules that are involved in activation of these channels and on the molecular characteristics of the channel. This will improve strategies aimed at developing new selective pharmacological agents and understanding the activation mechanism and functions of these channels in physiological systems.