Dr Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, Pakistan.
Pharm Biol. 2013 Mar;51(3):383-90. doi: 10.3109/13880209.2012.732582.
In the course of searching hepatoprotective agents from natural sources, the protective effect of chemical constituents of the marine brown alga Spatoglossum variabile Figaro et DE Notar (Dictyoaceae) against CCl₄-induced liver damage in Wistar rats was investigated. The compounds were first investigated for in vitro radical scavenging potential and were also tested for β-glucuronidase inhibition to further explore the relationship between hepatoprotection and antiradical potential.
The compounds cinnamic acid esters 1 and 2 and aurone derivatives 3 and 4 were first investigated for in vitro radical scavenging potential against 1,1-diphenyl-2-picrylhydrazyl radicals (DPPH), and superoxide anion radicals. In vivo hepatoprotective studies were performed in seven groups (n = 6) of Wistar rats. The test groups were pretreated with compounds (10 mg/kg body weight, po) orally for 30 min before the intraperitoneal administration of a dose of 20% CCl₄ diluted with dietary cooking oil. Moreover, compounds were also tested for β-glucuronidase inhibition to explore the relationship between hepatoprotection and radical scavenging potential.
The test compounds 1-4 were found to exhibit antiradical activity against 1,1-diphenyl-2-picrylhydrazyl radicals with IC₅₀ values ranging between 54 and 138 µM, whereas aurone derivatives 3 and 4 additionally exhibited superoxide anion scavenging effects with IC₅₀ values of 95 and 87 µM, respectively. In addition, these compounds were found to be weak inhibitors of xanthine oxidase (IC₅₀ ≥1000 µM). In animal model, pretreatment with compounds 2-4 significantly blocked the CCl₄-induced increase in the levels of the serum biochemical markers.
It appears that the hepatoprotection afforded by these compounds was mainly due to their radical scavenging activity that protected the cells from the free radicals generated by CCl₄-induced hepatotoxicity.
在从天然来源中寻找保肝剂的过程中，研究了海洋棕色海藻 Spatoglossum variabile Figaro et DE Notar（Dictyoaceae）的化学成分对 Wistar 大鼠 CCl₄ 诱导肝损伤的保护作用。首先研究了这些化合物的体外清除自由基的潜力，并测试了它们对β-葡萄糖醛酸酶的抑制作用，以进一步探讨保肝作用与抗自由基潜力之间的关系。
首次研究了肉桂酸酯 1 和 2 以及奥rone 衍生物 3 和 4 对 1,1-二苯基-2-苦基肼自由基（DPPH）和超氧阴离子自由基的体外清除自由基的潜力。在 Wistar 大鼠的七个实验组（n = 6）中进行了体内保肝研究。实验组在腹腔注射 20% CCl₄ 与膳食食用油混合液前 30 分钟，经口给予化合物（10mg/kg 体重）预处理。此外，还测试了化合物对β-葡萄糖醛酸酶的抑制作用，以探讨保肝作用与清除自由基潜力之间的关系。
发现测试化合物 1-4 对 1,1-二苯基-2-苦基肼自由基具有抗自由基活性，IC₅₀ 值在 54 到 138 μM 之间，而奥rone 衍生物 3 和 4 还具有超氧阴离子清除作用，IC₅₀ 值分别为 95 和 87 μM。此外，这些化合物被发现是黄嘌呤氧化酶的弱抑制剂（IC₅₀ ≥1000 μM）。在动物模型中，化合物 2-4 的预处理显著阻止了 CCl₄ 诱导的血清生化标志物水平的升高。
这些化合物提供的保肝作用主要归因于它们的清除自由基活性，该活性可保护细胞免受 CCl₄ 诱导的肝毒性产生的自由基的伤害。
