Gerencer Marijan, Turecek Peter L, Kistner Otfried, Mitterer Artur, Savidis-Dacho Helga, Barrett Noel P
Biomedical Research Center, Baxter AG, Uferstrasse 15, A-2304 Orth/D., Austria.
Antiviral Res. 2006 Nov;72(2):153-6. doi: 10.1016/j.antiviral.2006.03.008. Epub 2006 Apr 18.
We have isolated a substance with anti-retroviral activity from the freshly prepared crude extract of Chelidonium majus L. (greater celandine) by 9-aminoacridine precipitation method and ion exchange chromatography using Dowex-50W/H+ resin followed by the gel filtration on Sephadex-75 column. Elemental and phenol/sulfuric acid method analyses as well as the mass spectrometry of the purified substance indicated that it may represent a low-sulfated poly-glycosaminoglycan moiety with molecular weight of approximately 3800 Da. The substance prevented infection of human CD4+ T-cell lines AA2 and H9 with HIV-1 at concentration of 25 microg/mL as well as the cell-to-cell virus spread in H9 cells continuously infected with HIV-1, as determined by the measurement of reverse transcriptase activity and p24 content in cell cultures. Furthermore, we have shown in a murine AIDS model that the treatment with purified substance significantly prevented splenomegaly and the enlargement of cervical lymph nodes in C57Bl/6 mice chronically infected with the pool of murine leukemia retroviruses. The mechanism(s) of anti-retroviral activity of this substance have to be elucidated.
我们通过9-氨基吖啶沉淀法、使用Dowex-50W/H+树脂的离子交换色谱法,随后在Sephadex-75柱上进行凝胶过滤,从新鲜制备的白屈菜粗提物中分离出了一种具有抗逆转录病毒活性的物质。对纯化物质的元素分析、苯酚/硫酸法分析以及质谱分析表明,它可能是一种低硫酸化的聚糖胺聚糖部分,分子量约为3800 Da。通过测量细胞培养物中的逆转录酶活性和p24含量确定,该物质在浓度为25μg/mL时可防止人CD4+ T细胞系AA2和H9被HIV-1感染,以及防止在持续感染HIV-1的H9细胞中细胞间病毒传播。此外,我们在小鼠艾滋病模型中表明,用纯化物质治疗可显著预防慢性感染鼠白血病逆转录病毒库的C57Bl/6小鼠出现脾肿大和颈部淋巴结肿大。该物质抗逆转录病毒活性的机制有待阐明。