牛膝多糖硫酸酯体外和体内抗艾滋病病毒作用

Anti-HIV activities of Achyranthes bidentata polysaccharide sulfate in vitro and in vivo

牛膝多糖硫酸酯(Achyranthes bidentatapolysaccharide sulfate,ABPS)为牛膝多糖经硫酸酯化修饰后获得的产物,其结构清楚、理化性质稳定及分子质量小,具有抗单纯疱疹病毒、柯萨奇病毒和乙型肝炎病毒等作用。本文研究其在体外和体内的抗艾滋病病毒1型(human immunodeficiency virus type 1,HIV-1)活性。体外采用3H掺入法和酶联免疫吸附法测定ABPS对HIV-1逆转录酶和整合酶的活性,其半数抑制浓度(50%inhibiting concentrations,IC50)分别为(2.948±0.556)μmol.L-1和(0.155±0.030)μmol.L-1,但25μmol.L-1ABPS对HIV-1蛋白酶无效。ABPS在MT-4细胞培养内对HIV-1实验病毒株IIIB和在人外周血单核细胞培养内对AZT耐药病毒株的急性感染有较强的抑制作用,但在HIV-1 IIIB慢性感染的H9细胞培养中则无效。血清药理学研究表明,单次腹腔注射大鼠ABPS125 mg.kg-1或连续腹腔注射小鼠ABPS3 mg.kg-1(qd×20)后鼠血清在MT-4细胞培养内对HIV-1 P24抗原都有抑制作用,但口服ABPS生物利用度低,灌胃大鼠ABPS 2 g.kg-1或灌胃小鼠ABPS 300 mg.kg-1无效。实验结果提示ABPS有抗HIV-1作用,有可能用于防治HIV-1感染,值得进一步研究。

Achyranthes bidentata polysaccharide sulfate （ABPS） was a sulfated derivate derived from Achyranthes bidentata polysaccharide （ABP） which was isolated and identified from Chinese herb Achyranthes bidentata. The anti human immunodeficiency virus type 1 （ HIV-1 ） activities were studied in vitro and in vivo. ABPS was found to inhibit HIV-1 reverse transcriptase and integrase with the 50% inhibiting concentration （ IC50 ） of （2. 948 ± 0. 556 ） μmol· L^-1 and （0. 155±0. 030 ） μmol· L^-1, respectively, but the parent compound ABP was not effective. ABPS inhibited HIV-1 P24 antigen with IC50 of （0. 082 ±0. 044） μmol· L^-1 and selective index （SI） of 〉 （358 ± 148） in MT-4 cell cultures acutely infected with HIV-1 IIIB virus, and with IC50 of （ 11.80±5.90） μmol· L^-1 and SI of 〉 （24. 2 ± 12.1 ） in PBMC cell cultures acutely infected with clinical isolated zidovudine resistant HIV-1 virus, but there was no activity even at its concentration of 500 μmol· L^-1 in latent infection of H9/ HIV-1 IIIB cell cultures. 5% sera taken from rats after intraperitoneal injection from rats with ABPS 125 mg · kg^-1 once or mice with 3 mg· kg^-1 qd for 20 days effectively inhibited HIV-1 P24 in MT-4 cell cultures, but those had no inhibitory effect when given orally. The results suggested that ABPS is a promising HIV-1 inhibitor, active on HIV-1 reverse transcrlptase, integrase in vitro and HIV-1 P24 antigens in cell cultures, it was well absorbed by intraperitoneal injection but poor in oral bioavailability. It warrants further study.