کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
8738615 1591731 2018 26 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Perillyl alcohol exhibits in vitro inhibitory activity against Plasmodium falciparum and protects against experimental cerebral malaria
ترجمه فارسی عنوان
پروپیللی الکل دارای فعالیت مهاری در برابر ویروس پلاسمودیوم فالسیپاروم و محافظت در برابر بیماری مالاریا مغزی است
موضوعات مرتبط
علوم زیستی و بیوفناوری ایمنی شناسی و میکروب شناسی میکروبیولوژی و بیوتکنولوژی کاربردی
چکیده انگلیسی
The development of new drugs is one of the strategies to control malaria. Isoprenoid biosynthesis in Plasmodium falciparum is an essential pathway for parasite survival, and is therefore a potential target for new antimalarial drugs. Indeed, plant-derived secondary metabolites, such as terpenes, exhibit antimalarial activity in vitro by inhibiting isoprenoid biosynthesis in P. falciparum. In this study, the in vitro antiplasmodial activity of perillyl alcohol (POH) was evaluated, along with its in vitro toxicity and its effect on the isoprenylation process. In addition, the efficacy of intranasally administered POH in preventing Plasmodium berghei ANKA-induced experimental cerebral malaria (ECM) was determined. The 50% inhibitory concentrations of POH for 3D7 and K1 P. falciparum were 4.8 µM and 10.4 µM, respectively. POH inhibited farnesylation of 20-37 kDa proteins in P. falciparum (3D7), but no toxic effects in Vero cells were observed. A 500 mg/kg/d dose of POH had no effect on P. berghei ANKA parasitaemia, but showed marked efficacy in preventing ECM development (70% survival compared with 30% for untreated animals). This effect was associated with the downregulation of cerebrovascular inflammation and damage, with marked decreases in brain leucocyte accumulation and the incidence of brain microhaemorrhage. POH also downregulated interleukin (IL)-10, IL-6, tumour necrosis factor-α, interferon-γ, IL-12 and monocyte chemoattractant protein-1 levels in the brain and spleen. In conclusion, POH shows antiplasmodial activity in vitro and, despite there being no evidence of antiplasmodial activity in vivo following intranasal administration, POH prevented cerebrovascular inflammation/damage and expression of pro-inflammatory cytokines.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: International Journal of Antimicrobial Agents - Volume 51, Issue 3, March 2018, Pages 370-377
نویسندگان
, , , ,