Agrawal Shyam Sunder, Gullaiya Sumeet, Dubey Vishal, Singh Varun, Kumar Ashok, Nagar Ashish, Tiwari Poonam
Department of Pharmacology, Delhi Institute of Pharmaceutical Sciences and Research (DIPSAR), Pushp Vihar, Sector 3, M. B. Road, New Delhi 110017, India.
Cardiovasc Psychiatry Neurol. 2012;2012:942981. doi: 10.1155/2012/942981. Epub 2012 Aug 15.
Study was undertaken to evaluate the neurodegenerative defending potential of curcumin (CUR), demethoxycurcumin (DMC), and bisdemethoxycurcumin (BDMC) on 6-hydroxydopamine-(6-OHDA) induced Parkinsonism model in rats. Curcuminoids were administered (60 mg/kg, body weight, per oral) for three weeks followed by unilateral injection of 6-OHDA on 22nd day (10 μg/2 μL) into the right striatum leading to extensive loss of dopaminergic cells. The behavioral observations, biochemical markers, quantification of dopamine (DA), DOPAC, and HVA followed by dopamine (D(2)) receptor binding assay and tyrosine hydroxylase (TH, using immunohistochemistry) were evaluated using HPLC after three weeks of lesion. Pretreated animals showed significant protection against neuronal degeneration compared to lesion animals by normalizing the deranged levels of biomarkers and showed the potency in the order CUR > DMC > BDMC. The same order of effectiveness was observed in D(2) receptors binding assay and TH immunohistochemistry study. We conclude that curcuminoids appear to shield progressive neuronal degeneration from increased oxidative attack in 6-OHDA-lesioned rats through its free radical scavenging mechanism, and DA, DOPAC, and HVA enhancing capabilities in the sequence of efficacy CUR > DMC > BDMC. Further, curcuminoids may have potential utility in treatment of many more oxidative stress-induced neurodegenerative disorders.
本研究旨在评估姜黄素(CUR)、去甲氧基姜黄素(DMC)和双去甲氧基姜黄素(BDMC)对6-羟基多巴胺(6-OHDA)诱导的大鼠帕金森病模型的神经退行性保护潜力。给予姜黄素类化合物(60毫克/千克体重,口服),持续三周,然后在第22天向右侧纹状体单侧注射6-OHDA(10微克/2微升),导致多巴胺能细胞大量损失。在损伤三周后,通过高效液相色谱法评估行为观察、生化标志物、多巴胺(DA)、3,4-二羟基苯乙酸(DOPAC)和高香草酸(HVA)的定量,随后进行多巴胺(D₂)受体结合测定和酪氨酸羟化酶(TH,使用免疫组织化学法)检测。与损伤动物相比,预处理动物通过使生物标志物的紊乱水平正常化,对神经元变性表现出显著的保护作用,并且显示出的效力顺序为CUR>DMC>BDMC。在D₂受体结合测定和TH免疫组织化学研究中也观察到相同的有效性顺序。我们得出结论,姜黄素类化合物似乎通过其自由基清除机制,在6-OHDA损伤的大鼠中,保护神经元免受氧化攻击增加导致的进行性变性,并且在效力顺序为CUR>DMC>BDMC的情况下增强DA、DOPAC和HVA的能力。此外,姜黄素类化合物可能在治疗更多氧化应激诱导的神经退行性疾病方面具有潜在用途。