Wound healing activity and docking of glycogen-synthase-kinase-β-protein with isolated triterpenoid lupeol in rats
Wound healing activity and docking of glycogen-synthase-kinase-β-protein with isolated triterpenoid lupeol in rats
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DOI：
10.1016/j.phymed.2007.11.017
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发表时间：
2008-09-01
期刊：
影响因子：
7.9
通讯作者：
Swamy, H. M. Kumara
中科院分区：
文献类型：
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作者：
Harish, B. G.;Krishna, V.;Swamy, H. M. Kumara
通过瑞士白化病大鼠（175-225 g）的切除、切开和死腔创伤模型，筛选从南蛇藤叶的石油醚提取物中分离的三萜化合物羽扇豆醇的创伤愈合活性（8 mg/ml的0.2%藻酸钠凝胶）。在羽扇豆醇治疗组中，伤口愈合活性（17.83 +/- 0.48）比标准皮肤软膏呋喃西林（18.33 +/- 0.42）更显著。与对照组相比，切口伤口上皮化更快，伤口收缩率更高（571.50 +/- 5.07）。在死腔创伤模型中，羽扇豆醇处理的动物的肉芽组织的重量也增加，表明胶原化增加和单核细胞的缺乏。通过Writ信号传导途径，分离的羽扇豆醇分子和标准药物呋喃西林与糖原合成酶激酶3-β蛋白的比较对接也支持羽扇豆醇的创伤愈合性质。GSK 3-β的激活结构域由Tyr 216和活性口袋中的残基Asn 64、Gly 65、Ser 66、Phe 67、Gly 68、Val 70、Lys 85、Leu 132、Val 135、Asp 181组成，与羽扇豆醇对接，扭转自由度为0.5单位，拉马克遗传算法显示抑制常数为1.38 × 10（-7）。呋喃西林的抑制常数仅为1.35 × 10 ~（-4）。(C)2007年，Elsevier GmbH。All rights reserved.
A triterpene compound lupeol isolated from petroleum ether extract of leaves of Celastrus paniculatus was screened for wound healing activity (8 mg/ml of 0.2% sodium alginate gel) by excision, incision and dead space wound models on Swiss Albino rats (175-225 g). In lupeol treated groups wound healing activity was more significant (17.83 +/- 0.48) than the standard skin ointment nitrofurazone (18.33 +/- 0.42). Epithelialization of the incision wound was faster with a high rate of wound contraction (571.50 +/- 5.07) as compared with the control group. In dead space wound model also the weight of the granulation tissue of the lupeol treated animal was increased indicating increase of collagenation and absence of monocytes.The comparative docking of isolated lupeol molecule and standard drug nitrofurazone to glycogen synthase kinase3-beta protein by Writ signaling pathway also supported the wound healing property of lupeol. The activation domain of GSK3-beta consisted of Tyr216, with residues Asn64, Gly65, Ser66, Phe67, Gly68, Val70, Lys85, Leu132, Val135, Asp181 in the active pocket docked with lupeol at the torsional degree of freedom 0.5 units with Lamarckian genetic algorithm showed the inhibition constant of 1.38 x 10(-7). The inhibition constant of nitrofurazone was only 1.35 x 10(-4). (C) 2007 Elsevier GmbH. All rights reserved.