Department of Pharmaceutics, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160014, India.
Food Chem Toxicol. 2011 Nov;49(11):2906-13. doi: 10.1016/j.fct.2011.08.006. Epub 2011 Aug 25.
Aluminium, a well established neurotoxicant, is reported to be involved in the aetiology of Alzheimer's disease (AD) due to its easy admittance and accumulation in central nervous system (CNS). Simultaneous curcumin treatment during the induction of neurotoxicity by AlCl(3) is reported to provide protection. However, the therapeutic potential of curcumin in terms of reversing the neuronal damage once induced is limited due to its compromised bioavailability (BA). We prepared solid lipid nanoparticles of curcumin (C-SLNs) with enhanced BA (32-155 times) and investigated its therapeutic role in alleviating behavioural, biochemical and histochemical changes upon oral administration (100mg/kg) of AlCl(3) in male Lacca mice. Adverse effects of AlCl(3) were completely reversed by oral administration of C-SLNs. Treatment with free curcumin showed ≤ 15% recovery in membrane lipids (LPO) and 22% recovery in acetylcholinesterase (AChE) with respect to AlCl(3) treated group. C-SLNs showed significantly better results (97.46% and 73% recovery in LPO and AChE) at a dose of 50mg/kg, and the results were comparable (p ≤ 0.001) to those achieved with rivastigmine. Histopathology of the brain sections of C-SLNs treated groups also indicated significant improvement. Study highlights the potential of C-SLNs for treatment of AD.
铝是一种被广泛认可的神经毒素,由于其易于进入和在中枢神经系统(CNS)中的积累,被认为与阿尔茨海默病(AD)的发病机制有关。有报道称,在氯化铝(AlCl3)诱导神经毒性的同时进行姜黄素治疗可以提供保护。然而,由于其生物利用度(BA)受损,姜黄素在逆转诱导后神经元损伤方面的治疗潜力有限。我们制备了具有增强 BA(32-155 倍)的姜黄素固体脂质纳米粒(C-SLNs),并研究了其在经口给予(100mg/kg)氯化铝(AlCl3)后缓解雄性 Lacca 小鼠行为、生化和组织化学变化方面的治疗作用。经口给予 C-SLNs 可完全逆转 AlCl3 的不良反应。与 AlCl3 处理组相比,游离姜黄素处理仅使膜脂质(LPO)恢复了≤15%,乙酰胆碱酯酶(AChE)恢复了 22%。C-SLNs 在 50mg/kg 剂量下显示出明显更好的效果(LPO 和 AChE 分别恢复了 97.46%和 73%),其结果与 rivastigmine 相当(p≤0.001)。C-SLNs 治疗组的脑组织切片组织病理学也表明有显著改善。该研究强调了 C-SLNs 治疗 AD 的潜力。