Kurokawa M, Basnet P, Ohsugi M, Hozumi T, Kadota S, Namba T, Kawana T, Shiraki K
Department of Virology, Toyama Medical and Pharmaceutical University, Sugitani, Toyama, Japan.
J Pharmacol Exp Ther. 1999 Apr;289(1):72-8.
Rhus javanica, a medicinal herb, has been shown to exhibit oral therapeutic anti-herpes simplex virus (HSV) activity in mice. We purified two major anti-HSV compounds, moronic acid and betulonic acid, from the herbal extract by extraction with ethyl acetate at pH 10 followed by chromatographic separations and examined their anti-HSV activity in vitro and in vivo. Moronic acid was quantitatively a major anti-HSV compound in the ethyl acetate-soluble fraction. The effective concentrations for 50% plaque reduction of moronic acid and betulonic acid for wild-type HSV type 1 (HSV-1) were 3.9 and 2.6 microgram/ml, respectively. The therapeutic index of moronic acid (10.3-16.3) was larger than that of betulonic acid (6.2). Susceptibility of acyclovir-phosphonoacetic acid-resistant HSV-1, thymidine kinase-deficient HSV-1, and wild-type HSV type 2 to moronic acid was similar to that of the wild-type HSV-1. When this compound was administered orally to mice infected cutaneously with HSV-1 three times daily, it significantly retarded the development of skin lesions and/or prolonged the mean survival times of infected mice without toxicity compared with the control. Moronic acid suppressed virus yields in the brain more efficiently than those in the skin. This was consistent with the prolongation of mean survival times. Thus, moronic acid was purified as a major anti-HSV compound from the herbal extract of Rhus javanica. Mode of the anti-HSV activity was different from that of ACV. Moronic acid showed oral therapeutic efficacy in HSV-infected mice and possessed novel anti-HSV activity that was consistent with that of the extract.
中药盐肤木已被证明在小鼠中具有口服治疗抗单纯疱疹病毒（HSV）的活性。我们通过在pH 10条件下用乙酸乙酯萃取，随后进行色谱分离，从该草药提取物中纯化出两种主要的抗HSV化合物，齐墩果酸和桦木酸，并检测了它们在体外和体内的抗HSV活性。齐墩果酸是乙酸乙酯可溶部分中主要的抗HSV化合物。齐墩果酸和桦木酸对野生型1型单纯疱疹病毒（HSV-1）的50%蚀斑减少有效浓度分别为3.9和2.6微克/毫升。齐墩果酸的治疗指数（10.3 - 16.3）大于桦木酸（6.2）。阿昔洛韦 - 膦甲酸耐药的HSV-1、胸苷激酶缺陷的HSV-1以及野生型2型单纯疱疹病毒对齐墩果酸的敏感性与野生型HSV-1相似。当每天给经皮肤感染HSV-1的小鼠口服该化合物三次时，与对照组相比，它显著延缓了皮肤损伤的发展和/或延长了感染小鼠的平均存活时间且无毒性。齐墩果酸抑制脑中病毒产量的效率高于皮肤中的病毒产量。这与平均存活时间的延长是一致的。因此，齐墩果酸作为一种主要的抗HSV化合物从盐肤木的草药提取物中被纯化出来。其抗HSV活性模式与阿昔洛韦不同。齐墩果酸在HSV感染的小鼠中显示出口服治疗效果，并具有与提取物一致的新型抗HSV活性。
