厚朴提取物、厚朴酚及和厚朴酚的抗氧化和抗衰老药理作用研究进展

厚朴系木兰科植物厚朴Magnolia officinalis或凹叶厚朴M.officinalis Rehd.et Wils.var.biloba的干燥干皮、根皮及枝皮,具有燥湿消痰、下气除满的功效。厚朴提取物、厚朴酚及和厚朴酚都具有抗炎、抗氧化和抗衰老作用,厚朴酚及和厚朴酚是厚朴抗炎、抗氧化和抗衰老的主要活性成分。它们的抗氧化能力是通过对自由基的直接清除作用以及提高机体的抗氧化酶活性间接猝灭自由基表现出来。因此厚朴提取物、厚朴酚及和厚朴酚能防治各种氧化应激性炎性疾病,长期应用可能有防治机体衰老发生发展的作用。综述厚朴提取物、厚朴酚及和厚朴酚的抗氧化和抗衰老药理作用研究进展,以期为抗氧化和抗衰老的新药研发提供依据。     

厚朴酚及和厚朴酚抗抑郁药理作用及机制的研究进展

动物实验证实厚朴酚及和厚朴酚具有防治急慢性抑郁作用,其主要机制是抗氧化和抗炎:通过直接清除自由基以及提高机体的核因子E2相关因子-2抗氧化信号通路和抗氧化酶活性间接清除自由基而抑制活性氧生成;通过阻滞磷脂酰肌醇-3蛋白激酶/蛋白激酶B,细胞外信号调节激酶/丝裂原活化蛋白激酶和把关受体/丝裂原活化蛋白激酶信号通路抑制炎性细胞因子表达和小胶质细胞、星形细胞的激活,保护脑神经。也可增强脑内5-羟色胺能神经功能,提高脑源性神经营养因子表达,促进海马神经再生,产生抗抑郁作用;还可下调抑郁时的下丘脑-垂体-肾上腺轴功能的亢进,改善抑郁样行为。     

厚朴酚与和厚朴酚对脑损伤的保护作用及其机制的研究进展

整体实验结果显示,厚朴酚与和厚朴酚对缺氧、缺血、缺血再灌注、出血、高热中暑和脓毒症引起的脑损伤有保护作用。离体实验也证实,厚朴酚与和厚朴酚能对抗化学性缺氧、葡萄糖缺乏、缺血再灌注、高热,以及过氧化氢(H₂O₂)、兴奋性神经递质 N-甲基-D-门冬氨酸(NMDA)和谷氨酸、三甲基锡引起的神经细胞损伤。这都提示,厚朴酚与和厚朴酚可能是通过直接清除氧自由基和提高机体的抗氧化酶活性而间接清除氧自由基,以及阻滞磷脂酰肌醇 3-激酶(PI3K)-蛋白激酶 B(Akt)、胞外信号调节激酶(ERK)-促分裂素原活化蛋白激酶(MAPK)和 Toll 样受体(TLR)/MAPK/核因子 κB(NF-κB)等信号通路而抑制炎性细胞因子表达,从而产生抗氧化和抗炎作用,进而发挥脑保护作用。此外,厚朴酚与和厚朴酚还可通过促进抑制性神经递质 γ-氨基丁酸的生物合成和增强 γ-氨基丁酸的受体结合能力,从而对抗兴奋性神经递质对神经细胞的伤害。该文综述了厚朴酚与和厚朴酚对脑损伤的保护作用及其机制,并对其研究进展做了分析。     

厚朴提取物、厚朴酚及和厚朴酚的抗炎作用及其机制研究进展

厚朴系木兰科植物厚朴Magnolia officinalis或凹叶厚朴M.officinalis var.biloba的干燥干皮、根皮及枝皮,具有燥湿消痰、下气除满的功效。厚朴提取物、厚朴酚及和厚朴酚是厚朴抗炎的主要活性成分,其抗炎机制有：阻滞磷脂酰肌醇-3激酶/蛋白激酶B（PI3K/Akt）、细胞外调节蛋白激酶/丝裂原活化蛋白激酶（ERK/MAPK）和把关受体-2/丝裂原活化蛋白激酶（TLR/MAPK）信号通路,抑制炎性细胞因子表达;还可通过直接抑制诱导型一氧化氮合酶（iNOS）、环氧化酶-2（COX-2）、5-脂氧化酶（5-LO）的酶活性,阻滞炎症介质一氧化氮、前列腺素（PGs）、白三烯（LTs）的合成和释放,以及抑制组织胺释放等,产生广谱的抗炎作用。厚朴提取物、厚朴酚及和厚朴酚的抗氧化活性也是其抗炎作用的主要机制之一。厚朴为常用的非毒性中药,可以把研究重点放在防治慢性的或退行性疾病的微炎症方面。     

和厚朴酚的心血管药理作用研究进展

和厚朴酚是二酚型疏水化合物,对糖尿病、血管紧张素II、脓毒症、烧伤、冠脉结扎缺血、缺血再灌注等引起的心肌损伤都有保护作用,能阻滞心肌肥厚和纤维化的发生发展。和厚朴酚能拮抗脂多糖或氧化型低密度脂蛋白引起的血管内皮细胞损伤,也能抑制血管平滑肌细胞增殖、迁移及血管重塑和血管新生,抑制气囊血管形成术诱导新内膜形成和血管狭窄,心血管保护作用的基本机制是抗氧化、抗炎、调血脂、降血糖和阻滞钙通道。和厚朴酚可以抑制高脂饮食引起的动脉粥样硬化形成和发展,还具有血管扩张和降压作用,因此在心血管系统疾病治疗方面有开发价值。     

中药厚朴中厚朴酚、和厚朴酚的毛细管区带电泳分析

本文采用毛细管区带电泳法（ＣＺＥ）,以硼酸－磷酸混合体系作为背景电解质,对中药厚朴中两种具有生物活性的酚类成分（厚朴酚、和厚朴酚）进行分离。经过实验条件的优化,在０．０３ ｍｏｌ·Ｌ~(－１)硼酸－０．０１ ｍｏｌ·Ｌ~(－１)磷酸－２０％乙醇（ｐＨ １０．８０）缓冲液,检测波长２９４ｎｍ条件下,厚朴酚、和厚朴酚在１２分钟内可获得基线分离。实验表明这种方法简便快速,准确可靠,采用外标法可同时对厚朴中的厚朴酚、和厚朴酚进行定量测定。     

中药厚朴及其成分厚朴酚与和厚朴酚体外抗各种球菌的药理作用研究进展

中药厚朴不同溶剂的粗提取物具有体外抗各种球菌的药理作用,其中厚朴石油醚和乙醇提取物的抗球菌作用最强.厚朴酚(magnolol)及和厚朴酚(honokiol)是中药厚朴抗球菌的主要活性成分,其中厚朴酚抗球菌作用稍强于和厚朴酚.厚朴酚及和厚朴酚均能抑制金黄色葡萄球菌(以下简称"金葡菌")的自溶酶和α-溶血素、肠毒素-A、肠毒素-B的表达,阻断金葡菌的自溶和抑制其黏附功能及毒力,阻滞球菌诱导宿主细胞的炎性损伤反应.厚朴酚及和厚朴酚均能抑制被膜态金葡菌合成和释放eDNA和PIA,进而抑制生物被膜的形成,降低球菌的自我保护能力,产生抗球菌作用.本文中综述了中药厚朴及其成分厚朴酚及和厚朴酚体外抗各种球菌的药理作用,并对其研究进展做了分析.     

厚朴叶中厚朴酚及和厚朴酚的提取与测定

目的：研究厚朴叶中厚朴酚及和厚朴酚的快速提取及测定.方法：采用正交实验用ASE300快速溶剂萃取机进行提取方法的研究,用高效液相色谱法（HPLC）进行厚朴酚及和厚朴酚的含量测定,流动相为甲醇-水（79∶21）,流速为1.0 mL·min^-1,检测波长为294 nm,柱温为23℃.结果：用100%乙醇、91℃的提取温度在快速萃取系统提取3次（20min/次）,厚朴叶中的厚朴酚、和厚朴酚以及总酚的提取率分别为89.51%,87.83%和87.31%.结论：较HPLC法快速提取及测定厚朴叶中厚朴酚及和厚朴酚的方法较好.     

厚朴酚及和厚朴酚的胃肠道药理作用及其机制的研究进展

厚朴酚及和厚朴酚是一对疏水性烯丙基联苯酚类结构的同分异构体,具有许多相同的药理作用,如抗炎、抗氧化、抗肿瘤、抗微生物等。厚朴酚及和厚朴酚是钙离子通道阻滞剂,能抑制胃肠道平滑肌收缩;也能促进胃动素和胃泌素分泌,增强胃肠道内Cajal间质细胞内质网上的三磷酸肌醇受体和兰尼碱受体的表达和受体活性,促进内质网释放钙离子,激活Cajal间质细胞的起搏电流,增强胃肠道的节律性收缩。因此。厚朴酚及和厚朴酚对胃排空和胃肠推进运动产生双向调节作用：当各种病理因子引起胃肠道运动功能低下时表现为促进胃排空和胃肠推进运动;当各种病理因子引起胃肠运动亢进时,表现为对抗亢进。加之它们的抗氧化和抗炎作用可保护肠黏膜免遭伤害,提高脓毒症所致的胃肠道运动障碍,也能对抗各种肠炎和泻药所致的腹泻。     

和厚朴酚神经保护作用的研究进展

和厚朴酚作为中药厚朴的主要活性成分之一,是一种多酚类化合物,具有抗炎、抗菌、抗肿瘤、抗氧化等多种作用.近年来发现,和厚朴酚对神经系统具有明显的保护作用.和厚朴酚易于通过血脑屏障,具有发展为广谱抗神经系统疾病药物的潜力.本文主要概述了目前和厚朴酚在神经保护方面的作用及机制,以期为后续的深入研究提供参考.     

Affective and Anxiety Disorders and Alcohol and Drug Dependence:

Depression and anxiety frequently coexist in patients with substance use disorders. This clinically-oriented article examiens the relationship between these conditions and emphasizes data showing that substances of abuse can cause signs and symptoms of both depression and anxiety. These substance-related syndromes appear to have a different course and prognosis than uncomplicated, independent anxiety and major depressive disorders, and clinicians should consider the role of alcohol and other drugs in all patients presenting with these complaints. The authors will also outline an approach for diagnosing and managing patients with the combination of a substance use and depressive or anxiety disorder.     

Synthesis and anti-nociceptive and anti-inflammatory effects of gaultherin and its analogs

The synthesis of gaultherin (1) and its analogs was carried out to provide 11 glycosides under phase-transfer catalytic conditions. The activities of all synthesized compounds were evaluated by nitric oxide production inhibitory assay in vitro. Methyl 2-O-(4-O-β-d-galactopyranosyl)-β-d-glucopyranosylbenzoate (5f) showed significantly anti-nociceptive and anti-inflammatory effects by the evaluation in vivo. Structure–activity relationships within these compounds were discussed.     

Modelling and simulation of variability and uncertainty in toxicokinetics and pharmacokinetics

Two important methodological issues within the framework of the variability and uncertainty analysis of toxicokinetic and pharmacokinetic systems are discussed: (i) modelling and simulation of the existing physiologic variability in a population; and (ii) modelling and simulation of variability and uncertainty when there is insufficient or not well defined (e.g. small sample, semiquantitative, qualitative and vague) information available. Physiologically based pharmacokinetic models are especially suited for separating and characterising the physiologic variability from the overall variability and uncertainty in the system. Monte Carlo sampling should draw from multivariate distributions, which reflect all levels of existing dependencies in the intact organism. The population characteristics should be taken into account. A fuzzy simulation approach is proposed to model variability and uncertainty when there is semiquantitative, qualitative and vague information about the model parameters and their statistical distributions cannot be defined reliably.     

成骨细胞的功能与损伤和骨质疏松的防治

骨质疏松是一种全身性骨骼疾病,导致骨折风险增加。成人的骨量通过破骨细胞的骨吸收和成骨细胞的骨形成作用来维持动态平衡,治疗骨质疏松症的理想策略是抑制破骨细胞的骨吸收和/或增强成骨细胞的骨形成功能。目前针对保护成骨细胞及增强其功能的骨质疏松疗法相对较少。因此,本文针对成骨细胞相关功能蛋白、各种细胞损伤机制（内质网应激、氧化应激、机械过载、微小RNA和长链非编码RNA的影响等）及骨质疏松的治疗与预防作一综述,以期为针对增强成骨细胞功能的骨质疏松治疗策略提供新思路。     

益生菌与肿瘤防治

益生菌广泛存在于自然界中,通过维持宿主体内菌群平衡、影响肠屏障功能和调节免疫应答等作用,提高宿主健康水平,被公认为"肠道健康卫士".一些益生菌可以增强机体的免疫功能,抑制致癌物质,影响肿瘤细胞的基因表达,对肿瘤具有拮抗作用.大量研究表明,益生菌在未来的肿瘤防治中有很好的应用和发展前景.     

Self-stimulation and amphetamine: Tolerance to d and l isomers and cross tolerance to cocaine and methylphenidate

The effects of the d and l isomers of amphetamine on self-stimulation responding were tested following acute and chronic administration. Tolerance and post-drug depression of responding occurred in tests with both isomers, indicating no role for p-hydroxynorephedrine (PHN) which is one of the metabolites of d-amphetamine. In the second experiment, d-amphetamine, methylphenidate and cocaine all produced quantitatively and qualitatively similar effects on self-stimulation responding following acute administration. Following chronic administration of d-amphetamine, animals showed tolerance to all three drugs, indicating cross-tolerance among them. These data are consistent with an hypothesis that tolerance and post-drug depression following chronic amphetamine treatment are the result of decreases in postsynaptic receptor sensitivity, which would lead to a decreased effectiveness of all three drugs, regardless of their pre-synaptic mechanisms.     

Acamprosate and naltrexone treatment effects on ethanol and sucrose seeking and intake in ethanol-dependent and nondependent rats

Rationale  Two pharmacotherapies are approved for treating alcohol craving (acamprosate and naltrexone), but both have shown mixed findings in animals and humans. Objectives  The present experiments utilized a “reinforcer blocking” approach (i.e., rats were able to consume ethanol during treatment) to better understand the efficacy of these treatments for ethanol seeking and drinking using ethanol-dependent and nondependent rats. Materials and methods  In “nondependent” experiments, drugs (acamprosate 50, 100, and 200 mg/kg; naltrexone 0.1, 0.3, and 1.0 mg/kg) were administered over 3-week periods prior to operant sessions with a low response requirement to gain access to reinforcers for 20 min. For “dependent” experiments, rats were made dependent in vapor/inhalation chambers. Results  Acamprosate and naltrexone had similar effects on intake in nondependent and dependent rats; neither drug was selective for ethanol over sucrose drinking. In nondependent animals, naltrexone was more efficacious at more doses than acamprosate, and acamprosate’s effects were limited to a dose that also had adverse effects on body weight. Both pharmacotherapies showed more selectivity when examining reinforcer seeking. In nondependent rats, acamprosate and naltrexone had response-attenuating effects in ethanol, but not sucrose, groups. In dependent animals, acamprosate had selective effects limited to a decrease in sucrose seeking. Naltrexone, however, selectively decreased ethanol-seeking in nondependent rats. Conclusions  The naltrexone-induced decreases in seeking suggested a change in incentive motivation which was selective for ethanol in nondependent rats. The “nondependent” paradigm may model early stages of “problem drinking” in humans, and the findings suggest that naltrexone could be a good intervention for this level of alcohol abuse and relapse prevention.     

Antiinfective and encrustation-inhibiting materials--myth and facts

Catheters, urethral and ureteral stents and other urological implants are frequently affected by encrustration and infection due to their permanent contact with urine. Indwelling urinary catheters provide a haven for microorganisms and thus require extensive monitoring. Several surface modification techniques have been proposed to improve the performance of devices including the immobilization of biomolecules, the incorporation of hydrophilic grafts to reduce protein adsorption, the creation of hydrophobic surfaces, the creation of microdomains to regulate cellular and protein adhesion, new polymers and antimicrobial coatings. Physico-chemical explanation to elucidate the mechanism of such encrustation or infection inhibiting materials is still not available. Our series of experiments showed a marked decrease of silver-activity in biological fluids which corresponds with the controversial clinical results obtained with silver coated urinary catheters. Rifampicin/minocycline coated catheters had very low activity against Gram-negative rods, enterococci and Candida spp., the main causing organisms of urinary catheter infection. Surface engineered materials and antimicrobial drug delivery systems will be the next generation of sophisticated urinary catheters and stents, if both efficacy as well as efficiency has been proved clinically.     

Alprazolam and lorazepam single and multiple-dose effects on psychomotor skills and sleep

Summary The effects of alprazolam 0.5 mg and lorazepam 2 mg on cognitive and psychomotor skills were assessed in twelve normal volunteer subjects in a randomised, double-blind, crossover design. Single and multiple dose effects were monitored using a battery of tests comprising critical flicker fusion threshold (CFFT), choice reaction time (CRT), simulated car tracking, and subjective ratings of perceived sedation (LARS) and of sleep behaviour (LSEQ). Compared with placebo baseline scores, treatment with lorazepam 2 mg (both single and multiple doses) resulted in a widespread impairment of CRT, tracking accuracy, and CFFT. Single doses of alprazolam 0.5 mg reduced CFFT with respect to the placebo baseline. Single and multiple dose treatment with both drugs resulted in subjective reports of sedation, a reduction of sleep onset latency, and improved sleep quality. Only lorazepam 2 mg significantly disrupted the integrity of behaviour on waking from sleep. These results suggest important pharmacodynamic differences between the two drugs in the doses used.