Tolo Festus M, Rukunga Geoffrey M, Muli Faith W, Njagi Eliud N M, Njue Wilson, Kumon Kazuko, Mungai Geoffrey M, Muthaura Charles N, Muli Joseph M, Keter Lucia K, Oishi Esau, Kofi-Tsekpo Mawuli W
Centre for traditional Medicine and Drug Research, Kenya Medical Research Institute, P.O. Box 54840, 00200 Nairobi, Kenya.
J Ethnopharmacol. 2006 Mar 8;104(1-2):92-9. doi: 10.1016/j.jep.2005.08.053. Epub 2005 Sep 29.
Herpes simplex virus (HSV) infection is a major opportunistic infection in immunosuppressed persons. It is therefore a serious disease in high HIV/AIDS prevalence areas as in sub-Saharan Africa where infections due to HSV have risen significantly. The development of resistant strains of HSV to the available drugs for infection management, as is evident in the first drug of choice acyclovir, has further compounded this situation. There is therefore an urgent need to identify and develop new alternative agents for management of HSV infections, more so, for those due to resistant strains. We report here on an aqueous total extract preparation from the roots of Carissa edulis (Forssk.) Vahl (Apocynaceae), a medicinal plant locally growing in Kenya that has exhibited remarkable anti-HSV activity in vitro and in vivo for both wild type and resistant strains of HSV. The extract significantly inhibited formation of plaques in Vero E6 cells infected with 100PFU of wild type strains of HSV (7401H HSV-1 and Ito-1262 HSV-2) or resistant strains of HSV (TK(-) 7401H HSV-1 and AP(r) 7401H HSV-1) by 100% at 50 microg/ml in vitro with minimal cell cytotoxicity (CC(50)=480 microg/ml). When the extract was examined for in vivo efficacy in a murine model using Balb/C mice cutaneously infected with wild type or resistant strains of HSV, the extract at an oral dose of 250 mg/kg significantly delayed the onset of HSV infections by over 50%. It also increased the mean survival time of treated infected mice by between 28 and 35% relative to the infected untreated mice (p<0.05 versus control by Student's t-test). The mortality rate for mice treated with extract was also significantly reduced by between 70 and 90% as compared with the infected untreated mice that exhibited 100% mortality. No acute toxicity was observed in mice at the oral therapeutic dose of 250 mg/kg. These results suggest that this herbal extract has potent anti-viral agents against herpes simplex viruses that can be exploited for development of an alternative remedy for HSV infections.
单纯疱疹病毒（HSV）感染是免疫抑制人群中的一种主要机会性感染。因此，在撒哈拉以南非洲等高HIV/AIDS流行地区，它是一种严重疾病，在这些地区，HSV感染显著增加。HSV对用于感染管理的现有药物产生耐药菌株，如首选药物阿昔洛韦的情况，使这种情况更加复杂。因此，迫切需要鉴定和开发用于管理HSV感染的新替代药物，尤其是针对耐药菌株引起的感染。我们在此报告一种从肯尼亚当地生长的药用植物大花假虎刺（Carissa edulis (Forssk.) Vahl，夹竹桃科）的根中制备的水提物，该提取物在体外和体内对野生型和耐药型HSV菌株均表现出显著的抗HSV活性。该提取物在体外以50μg/ml的浓度能100%显著抑制感染100PFU野生型HSV菌株（7401H HSV - 1和Ito - 1262 HSV - 2）或耐药型HSV菌株（TK(-) 7401H HSV - 1和AP(r) 7401H HSV - 1）的Vero E6细胞中噬斑的形成，且细胞毒性最小（CC(50)=480μg/ml）。当在使用经野生型或耐药型HSV皮肤感染的Balb/C小鼠的小鼠模型中检测该提取物的体内疗效时，口服剂量为250mg/kg的提取物显著延迟HSV感染的发作超过50%。与未治疗的感染小鼠相比，它还使治疗的感染小鼠的平均存活时间增加了28%至35%（与对照组相比，学生t检验p<0.05）。与表现出100%死亡率的未治疗感染小鼠相比，用提取物治疗的小鼠的死亡率也显著降低了70%至90%。在口服治疗剂量250mg/kg时，小鼠未观察到急性毒性。这些结果表明，这种草药提取物具有针对单纯疱疹病毒的有效抗病毒剂，可用于开发HSV感染的替代疗法。
