姜黄素-PLGA纳米粒提高口服给药生物利用度的研究

目的 研究乳酸/羟基乙酸共聚物（PLGA）纳米粒子提高姜黄素口服生物利用度。方法 采用乳液挥发法制备姜黄素-PLGA纳米粒;通过透射电镜（transmission electron microscope,TEM）观察纳米粒形态;采用动态光散射法（dynamic light scattering,DLS）测定纳米粒大小、表面电位（Zeta电位）;考察药物的体外稳定性以及药物释放行为;以大鼠口服灌胃给药方式考察姜黄素和姜黄素-PLGA纳米粒的体内药物生物利用度。结果 姜黄素-PLGA纳米粒粒度分布均匀,平均粒径大小约200 nm;姜黄素-PLGA纳米粒具有较高的载药量和包封率以及稳定性,体外药物释放实验结果显示具有一定的缓释效果;口服灌胃100 mg·kg^-1姜黄素和姜黄素-PLGA纳米粒,给药30 min之后,姜黄素-PLGA纳米粒给药组的血药浓度水平显著高于姜黄素组（P〈0.05）,药物生物利用度提高到原来的5.2倍。结论 姜黄素-PLGA纳米粒可以有效的提高姜黄素稳定性和口服给药生物利用度。     

Mitochondrial metals as a potential therapeutic target in neurodegeneration

Transition metals are critical for enzyme function and protein folding, but in excess can mediate neurotoxic oxidative processes. As mitochondria are particularly vulnerable to oxidative damage due to radicals generated during ATP production, mitochondrial biometal homeostasis must therefore be tightly controlled to safely harness the redox potential of metal enzyme cofactors. Dysregulation of metal functions is evident in numerous neurological disorders including Alzheimer''s disease, stroke, Parkinson''s disease, Huntington''s disease, amyotrophic lateral sclerosis and Friedrich''s ataxia. This review describes the mitochondrial metal defects in these disorders and highlights novel metal-based therapeutic approaches that target mitochondrial metal homeostasis in neurological disorders.

Linked Articles

This article is part of a themed issue on Mitochondrial Pharmacology: Energy, Injury & Beyond. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2014.171.issue-8     

Synthesis of [18O2]‐curcumin

Curcumin, a pigment isolated from rhizomes of Curcuma longa, is a potent cancer chemopreventive and chemotherapeutic agent and is now evaluated in phase III human clinical trials. This report describes an efficient synthesis of [¹⁸O₂]‐curcumin. [¹⁸O₂]‐Curcumin was prepared in three steps from 1‐iodo‐2‐methoxy‐4‐methylbenzene in an overall yield of 53%.     

Curcumin Protects against Cadmium-Induced Vascular Dysfunction,Hypertension and Tissue Cadmium Accumulation in Mice

Curcumin from turmeric is commonly used worldwide as a spice and has been demonstrated to possess various biological activities. This study investigated the protective effect of curcumin on a mouse model of cadmium (Cd)—induced hypertension, vascular dysfunction and oxidative stress. Male ICR mice were exposed to Cd (100 mg/L) in drinking water for eight weeks. Curcumin (50 or 100 mg/kg) was intragastrically administered in mice every other day concurrently with Cd. Cd induced hypertension and impaired vascular responses to phenylephrine, acetylcholine and sodium nitroprusside. Curcumin reduced the toxic effects of Cd and protected vascular dysfunction by increasing vascular responsiveness and normalizing the blood pressure levels. The vascular protective effect of curcumin in Cd exposed mice is associated with up-regulation of endothelial nitric oxide synthase (eNOS) protein, restoration of glutathione redox ratio and alleviation of oxidative stress as indicated by decreasing superoxide production in the aortic tissues and reducing plasma malondialdehyde, plasma protein carbonyls, and urinary nitrate/nitrite levels. Curcumin also decreased Cd accumulation in the blood and various organs of Cd-intoxicated mice. These findings suggest that curcumin, due to its antioxidant and chelating properties, is a promising protective agent against hypertension and vascular dysfunction induced by Cd.     

姜黄素对肠道屏障的作用及机制

姜黄素是一种从姜科植物的根茎中提取而得的橙黄色多酚类化学物质,是中药姜黄、郁金等的主要有效成分,被广泛用于食品添加、化妆品、染料等。近些年大量研究表明姜黄素还存在较高的医疗价值,具有抗炎、抗氧化、抗肿瘤、抗凋亡、抗纤维化、免疫调节等作用,可用于多种疾病[1],已逐渐成为国内外的一个研究热点。     

姜黄素修复脊髓损伤的信号通路研究进展

姜黄素是从中药姜黄中提取的天然多酚化合物,对于脊髓损伤的修复显示出良好的疗效。姜黄素可以抑制神经炎症反应;减少胶质瘢痕的形成;减少局部神经组织自由基释放和脂质过氧化;减少神经细胞凋亡和改善脊髓损伤微环境。综述目前姜黄素修复脊髓损伤研究所涉及8条信号通路（NF-κB、TLR4-TAK1-NF-κB、JAK/STAT、Nrf2、ERS、N-甲基-D-天冬氨酸受体-Ca²⁺诱导型一氧化氮合酶、SOX9和Wnt/β-catenin）及相关具有潜力的通路（mTOR）,为姜黄素治疗脊髓损伤作用机制的深入研究提供新思路。     

姜黄素纳米制剂在肿瘤治疗中的研究进展

姜黄素是一种天然的多酚类化合物,广泛存在于包括姜黄在内的多种草本植物中。它是一种天然的抗氧剂,具有许多的药理活性,安全有效,尤其是抗肿瘤作用受到广泛的关注。但由于姜黄素的水中溶解度差、光降解、化学不稳定以及生物利用度低等问题限制了其在临床的广泛应用。因此,需要开发适当的给药系统来解决这一问题。本文综述了近年来姜黄素纳米制剂在肿瘤治疗中的研究进展,重点阐述了其抗肿瘤纳米制剂的种类及其在细胞和动物实验中的应用,为进一步的研发提供依据。     

甘草次酸修饰姜黄素阳离子脂质体对肿瘤Walker256细胞的影响

目的：研究姜黄素及甘草次酸修饰姜黄素阳离子脂质体对Walker256细胞的影响。方法：不同浓度姜黄素与甘草次酸修饰姜黄素阳离子脂质体处理Walker256细胞后,采用CCK-8法检测细胞增殖抑制率;用流式细胞仪检测细胞吸收、细胞周期变化情况;Annexin V/PI双染法检测细胞凋亡;Western blot检测Wnt及β-catenin表达水平。结果：姜黄素和甘草次酸修饰姜黄素阳离子脂质体对肿瘤细胞Walker256均具有明显的抑制作用。与游离姜黄素相比,甘草次酸修饰姜黄素阳离子脂质体明显增强细胞对姜黄素的吸收,显著增强对Walker256细胞的增殖抑制、凋亡、细胞周期G2期的阻滞作用,明显下调Wnt及β-catenin的表达。结论：甘草次酸修饰姜黄素阳离子脂质体比游离姜黄素具有更强的抗肿瘤Walker256细胞的作用。