Singh Neha, Khullar Neeraj, Kakkar Vandita, Kaur Indu Pal
Department of Biotechnology, Panjab University, Chandigarh, India.
BioDrugs. 2014 Jun;28(3):297-312. doi: 10.1007/s40259-014-0086-1.
Curcumin, an established pleiotropic agent, has potential for hepatoprotection owing to its powerful antioxidant, anti-inflammatory, and antifibrogenic properties. However, its poor bioavailability limits its use in therapeutics. In this study, we aimed to package curcumin into solid lipid nanoparticles (C-SLNs) to improve its bioavailability and compare the efficacy of C-SLNs with that of free curcumin and silymarin, a well-established hepatoprotectant in clinical use, against carbon tetrachloride (CCl4)-induced hepatic injury in rats, post-induction. A self-recovery group to which no treatment was given was also employed for quantifying self-healing of hepatic tissue, if any.
C-SLNs (particle size 147.6 nm), prepared using a microemulsification technique, were administered to rats post-treatment with CCl4 (1 ml/kg body weight [BW] twice weekly for 2 weeks, followed by 1.5 ml/kg BW twice weekly for the subsequent 2 weeks). The extent of liver damage and repair in terms of histopathology and levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), oxidative stress markers (malondialdehyde, superoxide dismutase, and reduced glutathione) and a pro-inflammatory response marker, tumor necrosis factor (TNF)-α, were determined in both the CCl4 group and the treatment groups.
C-SLNs (12.5 mg/kg) significantly (p < 0.001-0.005) attenuated histopathological changes and oxidative stress, and also decreased induction of ALT, AST, and TNF-α in comparison with free curcumin (100 mg/kg), silymarin (25 mg/kg), and self-recovery groups.
Curcumin could be used as a therapeutic agent for hepatic disorders, provided it is loaded into a suitable delivery system.
姜黄素是一种公认的具有多种生物学活性的药物，因其强大的抗氧化、抗炎和抗纤维化特性而具有肝脏保护潜力。然而，其较差的生物利用度限制了它在治疗中的应用。在本研究中，我们旨在将姜黄素包裹于固体脂质纳米粒（C-SLNs）中以提高其生物利用度，并比较C-SLNs与游离姜黄素及水飞蓟素（临床常用的一种肝脏保护剂）对大鼠四氯化碳（CCl4）诱导的肝损伤的治疗效果。还设立了一个未接受任何治疗的自我恢复组，以量化肝组织的自我修复情况（若有）。
采用微乳化技术制备的C-SLNs（粒径147.6 nm），在大鼠接受CCl4处理后给药（每周两次，每次1 ml/kg体重[BW]，共2周，随后2周每周两次，每次1.5 ml/kg BW）。在CCl4组和各治疗组中，通过组织病理学以及丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）、氧化应激标志物（丙二醛、超氧化物歧化酶和还原型谷胱甘肽）和促炎反应标志物肿瘤坏死因子（TNF）-α的水平来确定肝损伤和修复程度。
与游离姜黄素（100 mg/kg）、水飞蓟素（25 mg/kg）和自我恢复组相比，C-SLNs（12.5 mg/kg）显著（p < 0.001 - 0.005）减轻了组织病理学变化和氧化应激，还降低了ALT、AST和TNF-α的诱导水平。
如果将姜黄素载入合适的递送系统，它可作为肝脏疾病的治疗药物。
