Mesaik M Ahmed, Murad Shahnaz, Ismail Zakiah, Abdullah Noor Rain, Gill H Kauar, Yousaf Muhammad, Siddiqui R Ali, Ahmad Aqeel, Choudhary M Iqbal
Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical Sciences, University of Karachi, Karachi 75270, Pakistan.
Mol Immunol. 2006 Apr;43(11):1855-63. doi: 10.1016/j.molimm.2005.10.020. Epub 2006 Jan 10.
Withanolide, coagulin-H (1), was evaluated for its effect on various cellular functions related to immune response including lymphocyte proliferation, and expression of interleukin-2 (IL-2) cytokine, and results were compared with prednisolone (2), a commonly used immune modulating drug. Coagulin-H (1) was found to have a powerful inhibitory effect on lymphocyte proliferation and Th-1 cytokine production. Inhibition of the phytohaemagglutinin (PHA)-activated T-cell proliferation by coagulin-H (1) was observed in a concentration dependent manner. A complete suppression of PHA-activated T-cell was observed at > or =2.5 microg/mL concentrations of compound (1) and this suppression activity was similar to that of prednisolone (2). Coagulin-H (1) also significantly inhibited IL-2 production by 80%. The interactions of coagulin-H (1) (a natural inhibitor) and prednisolone (2) (a drug) to IL-2 were also investigated in order to understand the differences in their effects on T-cell responses. This paper also describes the results of molecular docking study on IL-2 inhibition. Docking studies predicted that coagulin-H (1) binds to receptor binding site of IL-2 more effectively than prednisolone (2). Based on the computational and the experimental results, coagulin-H (1) was identified as a potential immunosuppressive candidate.
对睡茄内酯类化合物凝结素-H（1）进行了评估，以研究其对包括淋巴细胞增殖以及白细胞介素-2（IL-2）细胞因子表达在内的各种与免疫反应相关的细胞功能的影响，并将结果与常用的免疫调节药物泼尼松龙（2）进行比较。发现凝结素-H（1）对淋巴细胞增殖和Th-1细胞因子产生具有强大的抑制作用。观察到凝结素-H（1）对植物血凝素（PHA）激活的T细胞增殖的抑制呈浓度依赖性。在化合物（1）浓度≥2.5μg/mL时观察到PHA激活的T细胞被完全抑制，且这种抑制活性与泼尼松龙（2）相似。凝结素-H（1）还显著抑制IL-2的产生，抑制率达80%。为了解凝结素-H（1）（一种天然抑制剂）和泼尼松龙（2）（一种药物）对IL-2作用的差异，还研究了它们与IL-2的相互作用。本文还描述了对IL-2抑制的分子对接研究结果。对接研究预测，凝结素-H（1）比泼尼松龙（2）更有效地结合到IL-2的受体结合位点。基于计算和实验结果，凝结素-H（1）被确定为一种潜在的免疫抑制候选物。
