Sawamura Rie, Shimizu Tomomi, Sun Yi, Yasukawa Ken, Miura Motofumi, Toriyama Masaharu, Motohashi Shigeyasu, Watanabe Wataru, Konno Katsuhiko, Kurokawa Masahiko
Department of Biochemistry, School of Pharmaceutical Sciences, Kyushu University of Health and Welfare, Nobeoka, Japan.
Antivir Chem Chemother. 2010 Oct 28;21(1):33-41. doi: 10.3851/IMP1676.
Diarylheptanoids (AO-0002 [7-(4''-hydroxy-3''-methoxyphenyl)-1-phenyl-4E-hepten-3-one] and AO-0011 [(5S)-5-hydroxy-7-(4''-hydroxyphenyl)-1-phenyl-3-heptanone]) isolated from Alpinia officinarum have been reported to exhibit anti-influenza virus activity in vitro. Hence, efficacies against influenza virus infection and the mode of antiviral action were evaluated in vivo and in vitro, respectively.
In a murine influenza virus infection model, diarylheptanoids were orally administered three times daily to mice infected with influenza A/PR/8/34 virus for 6 days after infection. AO-0002 was examined for its antiviral activity against the wild types of influenza viruses A/PR/8/34 (H1N1), oseltamivir-resistant A/PR/8/34 (H1N1), A/Bangkok/93/03 (H1N1), A/Ishikawa/7/82 (H3N2), A/Fukushima/13/43 (H3N2), B/Singapore/222/79 and B/Fukushima/15/93 in plaque reduction or yield reduction assays. The mode of anti-influenza virus action was assessed by a virus adsorption assay, immunofluorescence assay of viral antigens, and inhibition of viral messenger RNA synthesis using real-time reverse transcriptase PCR.
AO-0002 at 100 mg/kg was significantly effective in reducing the body weight loss and prolonging survival times of infected mice without toxicity, but AO-0011 was not. AO-0002 at 30 and 100 mg/kg significantly reduced virus titres in bronchoalveolar lavage fluids of the lungs on days 3 and 6 after infection. AO-0002 exhibited anti-influenza virus activity against all viruses used, including the oseltamivir-resistant strain in vitro. The compound had no effect on virus adsorption or invasion into cells, but dose-dependently suppressed the expression of viral messenger RNA and antigens.
AO-0002 was suggested to have a different anti-influenza virus action to that of oseltamivir and was verified to show anti-influenza activity in vitro and in vivo.
从高良姜中分离出的二芳基庚烷类化合物（AO - 0002 [7-(4''-羟基-3''-甲氧基苯基)-1-苯基-4E-庚烯-3-酮]和AO - 0011 [(5S)-5-羟基-7-(4''-羟基苯基)-1-苯基-3-庚酮]）已被报道在体外具有抗流感病毒活性。因此，分别在体内和体外评估了它们对流感病毒感染的疗效及抗病毒作用方式。
在小鼠流感病毒感染模型中，感染甲型流感病毒A/PR/8/34的小鼠在感染后6天内，每天口服二芳基庚烷类化合物3次。在蚀斑减少或病毒产量减少试验中，检测AO - 0002对野生型流感病毒A/PR/8/34（H1N1）、耐奥司他韦的A/PR/8/34（H1N1）、A/曼谷/93/03（H1N1）、A/石川/7/82（H3N2）、A/福岛/13/43（H3N2）、乙型流感病毒B/新加坡/222/79和B/福岛/15/93的抗病毒活性。通过病毒吸附试验、病毒抗原免疫荧光试验以及使用实时逆转录聚合酶链反应抑制病毒信使核糖核酸合成来评估抗流感病毒作用方式。
100 mg/kg的AO - 0002能显著减轻感染小鼠的体重减轻并延长其存活时间，且无毒性，但AO - 0011则无此效果。30 mg/kg和100 mg/kg的AO - 0002在感染后第3天和第6天能显著降低肺支气管肺泡灌洗液中的病毒滴度。AO - 0002在体外对所有所使用的病毒，包括耐奥司他韦毒株均表现出抗流感病毒活性。该化合物对病毒吸附或侵入细胞没有影响，但能剂量依赖性地抑制病毒信使核糖核酸和抗原的表达。
AO - 0002被认为具有与奥司他韦不同的抗流感病毒作用，并且在体内和体外均被证实具有抗流感活性。
