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61.
目的观察姜黄素(curcumin)对糖基化终末产物(AGEs)诱导的软骨细胞凋亡及线粒体功能损伤的作用,并探讨相关机制是否与姜黄素上调过氧化物酶体增殖物激活受体-γ(PPARγ)相关。方法原代培养家兔膝关节软骨细胞;TUNEL染色法检测细胞凋亡;Rhodamine-123试剂盒检测线粒体跨膜电位(△Ψm);ATP试剂盒检测线粒体ATP生成;分光光度法检测caspase-3活性;Western blot检测PPARγ、细胞色素C、Bax及Bcl-2蛋白表达;real-time PCR检测PPARγmRNA含量;DNA-binding法检测PPARγ活性。结果 AGEs(200 mg·L-1)可明显诱导兔软骨细胞凋亡,同时线粒体跨膜电位(△Ψm)降低、ATP生成减少,caspase-3活性增加,细胞色素C释放增加,Bax/Bcl-2的比值增加;线粒体通透性转换孔的抑制剂环孢霉素A(Cs A,100 nmol·L-1)可以明显抑制AGEs诱导的细胞凋亡;PPARγ特异性激动剂吡格列酮及姜黄素均可明显抑制AGEs诱导的软骨细胞凋亡及线粒体功能损伤,给予PPARγ特异性抑制剂GW9662 10μmol·L-1预处理后,可以明显拮抗姜黄素的保护作用。同时,姜黄素可以明显上调AGEs诱导的PPARγ活性的降低,并伴随PPARγ相应的mRNA及蛋白表达水平的升高。结论姜黄素通过上调PPARγ,有效地保护AGEs诱导的软骨细胞线粒体损伤,从而抑制AGEs诱导的软骨细胞凋亡。 相似文献
62.
AbstractDeveloping drug formulations for poorly water-soluble drugs is a major challenge for pharmaceutical industries as the poor water solubility limits bioavailability of these drugs. Production of nanoparticles/microparticles of these drugs is one of the ways to improve dissolution rates by increasing interfacial area for dissolution. Curcumin, a compound obtained from the rhizome of curcuma longa (turmeric roots), is a pharmaceutically viable molecule. However, poor aqueous solubility limits its therapeutic use. In this work, we report studies conducted to continuously produce aqueous suspensions of curcumin nano/micro particles. Influence of process parameters such as ultrasound, additives, and solvent to antisolvent ratio on polymorphic outcome and morphology of precipitated particles has been investigated. Ultrasound was found to greatly influence the polymorphic form and the morphology of precipitated particles. Nucleation rates, mixing time, and solid–liquid interfacial energies were also estimated to understand the effect of various processing parameters on the precipitation process. 相似文献
63.
Pancreatic cancer is one of the most malignant cancers with a high mortality rate. Some types of pancreatic cancer cells overexpress epidermal growth factor receptor (EGFR), which is a potential target for anticancer agents. In this study, we examined the effect of epidermal growth factor (EGF)-conjugated liposomes containing curcumin (EGF-LP-Cur) on three different EGFR-expressed human pancreatic cancer cell lines, BxPC-3, Panc-1 and Mia Paca-2. We have demonstrated that it is feasible to prepare liposomal vesicles of EGF-LP-Cur and that it is stable in the liquid vehicle at ambient conditions for three weeks. In addition, the formulation of curcumin had higher cytotoxicity on BxPC-3 than on any other cells. It is also shown that the cellular uptake of curcumin on BxPC-3, which is essential for the cytotoxicity, is associated with EGFR-mediated mechanism of action. In summary, our results have showed that targeting EGFR with EGF-conjugated curcumin liposomes enhanced the antitumor activity of curcumin against human pancreatic cancer cells. 相似文献
64.
目的 优化RGD环肽修饰的姜黄素(curcumin,Cur)/黄芩苷(baicalin,Bai)共递送靶向纳米脂质体(RGD-Cur/Bai-Lip)的制备工艺并进行表征评价。方法 采用乙醇注入法制备RGD-Cur/Bai-Lip,首先通过Plackett-Burman筛选实验确定超声时间、胆脂比、水合温度作为制备RGD-Cur/Bai-Lip的关键因素,然后采用Box-Behnken响应面法进行工艺优化,以姜黄素包封率、黄芩苷包封率、总载药量为考察指标,采用AHP-复相关系数法-拉开档次法进行多指标组合赋权以确定各指标权重系数并计算综合评分,从而确定RGD-Cur/Bai-Lip的最优处方及关键工艺参数。最后对其形态、粒径电位、稳定性、体外释放度及溶血性等进行表征评价。结果 优选得到的最佳工艺为胆脂比1:12,水合温度60℃,探头超声时间为10 min。RGD-Cur/Bai-Lip外观澄清透明,呈亮黄色,对光可视淡蓝色乳光,透射电子显微镜下观察形态圆整、分散均匀。平均粒径为(101.10±0.62)nm,多分散系数(PDI)为0.191 0±0.014 3,Zeta电位为(1.59±0.07)mV,姜黄素包封率为(94.28±4.51)%,黄芩苷包封率为(76.93±1.35)%,总载药量为(2.27±0.09)%。7 d内稳定性良好,无溶血性,并具有一定的缓释作用。结论 优化处方后制备的RGD-Cur/Bai-Lip包封率高,粒径分布均匀,7 d内较稳定,无溶血性,并具有一定的缓释作用,为RGD-Cur/Bai-Lip的后续抗肝纤维化体内外研究提供了制剂基础。 相似文献
65.
66.
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。 相似文献
67.
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 相似文献68.
Xiurui Shen Xiaomei Yang Ying Zhu Xihuan Liu Hongliang Wen 《Journal of labelled compounds & radiopharmaceuticals》2014,57(11):658-659
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%. 相似文献
69.
Upa Kukongviriyapan Patchareewan Pannangpetch Veerapol Kukongviriyapan Wanida Donpunha Kwanjit Sompamit Praphassorn Surawattanawan 《Nutrients》2014,6(3):1194-1208
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. 相似文献
70.
朱佳杰 《中国中西医结合消化杂志》2021,(2)
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。 相似文献