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橙皮素共轭聚乙二醇化金纳米粒子在大鼠二乙基亚硝胺诱导的肝癌发生过程中抗炎和抗增殖潜在作用的研究。

Hesperetin conjugated PEGylated gold nanoparticles exploring the potential role in anti-inflammation and anti-proliferation during diethylnitrosamine-induced hepatocarcinogenesis in rats.

作者信息

Krishnan Gokuladhas, Subramaniyan Jayakumar, Chengalvarayan Subramani Pramila, Muralidharan Barath, Thiruvengadam Devaki

机构信息

Department of Biochemistry, University of Madras, Guindy Campus, Chennai 600 025, Tamilnadu, India.

Ragalakshmi Engineering College, Chennai 602105, Tamilnadu, India.

出版信息

Asian J Pharm Sci. 2017 Sep;12(5):442-455. doi: 10.1016/j.ajps.2017.04.001. Epub 2017 May 12.

Abstract

Liver cancer is the fifth most common cancer and one of the leading causes of death in the world, and second most common cause of death in men. Natural products emerge as the most enduring approaches in the development of anticancer targeting drug. Hesperetin (HP), one of the abundant flavonoids found naturally in citrus fruits, has received considerable attention in anti-cancer promotion and progression. The present study was conducted to decipher the role of 0.5 ml hesperetin conjugated gold nanoparticles (Au-mPEGS-HP NPs) during diethylnitrosamine (DEN)-induced hepatocarcinogenesis in male Wistar albino rats and shows the better antioxidant that possesses anti-inflammatory, anti-proliferation and anticarcinogenic properties and may modulate signaling pathways. The confirmation of polymer functionalized gold nanoparticles and drug loaded polymer gold nanoparticles were characterized by HR-TEM with EDAX, and DLS with Zeta potential techniques. The drug encapsulation efficiency and release properties were carried out in PBS at pH 7.4 for Au- mPEGS-HP and compared with the control pure hesperetin (HP). Here, we review the role of mast cell counts, tumor necrosis factor alpha (TNF-α), transcription factor nuclear factor-κB (NF-κB), levels of glycoconjugates, proliferating cell nuclear antigen (PCNA) and argyrophilic nucleolar organizing regions, are the master regulator of inflammation and proliferation, in the development of hepatocellular injury, liver fibrosis and HCC. DEN-administered animals showed increased mast cell counts, tumor necrosis factor alpha, transcription factor nuclear factor-κB, glycoconjugates, proliferating cell nuclear antigen, and argyrophilic nucleolar organizing regions. Whereas Au-mPEGS-HP NPs supplementation considerably suppressed all the above abnormalities. These results suggest that the Au-mPEGS-HP NPs exhibited the better potential anticancer activity by inhibiting cell inflammation and proliferation in DEN-induced hepatocellular carcinogenesis.

摘要

肝癌是全球第五大常见癌症,也是主要死因之一,在男性中是第二大常见死因。天然产物是抗癌靶向药物开发中最持久的方法之一。橙皮素(HP)是柑橘类水果中天然存在的丰富黄酮类化合物之一,在抗癌促进和进展方面受到了相当多的关注。本研究旨在阐明0.5毫升橙皮素共轭金纳米颗粒(Au-mPEGS-HP NPs)在二乙基亚硝胺(DEN)诱导的雄性Wistar白化大鼠肝癌发生过程中的作用,并表明其具有更好的抗氧化性能,具有抗炎、抗增殖和抗癌特性,可能调节信号通路。通过带有能谱分析的高分辨透射电子显微镜(HR-TEM)以及动态光散射和zeta电位技术对聚合物功能化金纳米颗粒和载药聚合物金纳米颗粒进行了表征。在pH 7.4的磷酸盐缓冲液(PBS)中对Au-mPEGS-HP的药物包封效率和释放特性进行了研究,并与对照纯橙皮素(HP)进行了比较。在此,我们综述了肥大细胞计数、肿瘤坏死因子α(TNF-α)、转录因子核因子κB(NF-κB)、糖缀合物水平、增殖细胞核抗原(PCNA)和嗜银核仁组织区在肝细胞损伤、肝纤维化和肝癌发生发展中的作用,它们是炎症和增殖的主要调节因子。给予DEN的动物肥大细胞计数、肿瘤坏死因子α、转录因子核因子κB、糖缀合物、增殖细胞核抗原和嗜银核仁组织区均增加。而补充Au-mPEGS-HP NPs可显著抑制上述所有异常情况。这些结果表明,Au-mPEGS-HP NPs在DEN诱导的肝细胞癌发生过程中通过抑制细胞炎症和增殖表现出更好的潜在抗癌活性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4c0/7032104/a7c2919725aa/ajps433-ga-5001.jpg

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