30种滇西植物β-羟高铁血红素形成抑制活性
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摘要
疟疾是严重危害人类健康的寄生虫病之一,据世界卫生组织报道每年有数十万人因疟疾而死亡,我国疟疾防治工作虽然取得了长足发展,但在中国云南边境地区和中国西藏林芝地区本地疟疾病例依然存在,再加上西藏自治区和云南省地理位置特殊,与周边疟疾高发的国家接壤,边民来往十分频繁,传染源输入无法杜绝。为了发现植物来源的新型抗疟疾天然产物,该研究依次用75%乙醇和蒸馏水对30种滇西植物进行回流提取,并采用β-羟高铁血红素形成抑制实验对这些样品进行抗疟活性筛选。结果表明:在供试的30种植物中,玉叶金花、回心草以及云南甘草等19种植物粗提物具有不同程度的β-羟高铁血红素形成抑制活性,具有抗疟活性的植物种类涉及17个科、19个属。其中,虾子花、东方紫金牛、姜花水提物以及反瓣老鹳草地下部分醇提物的活性较好,其IC_(50)值分别为796.0、951.0、1 033.0、1 388.9μg·mL~(-1),值得进一步深入研究。虾子花、东方紫金牛的HPLC分析结果显示,其活性成分应为酚性成分。
Malaria is a parasitic disease that seriously endangers human health. According to the world health organization,hundreds of thousands of people died due to malaria each year. Although the prevention and treatment of malaria in China has made great progress,the local malaria cases still exist in the border areas of Yunnan and Nyingchi of Tibet,China. In addition to the special geographical locations of Tibet and Yunnan,China shares borders with neighboring countries with high incidence of malaria,and the border residents have frequent contacts,so the source of infection cannot be eliminated. Therefore,the situation of malaria prevention and control in China is still not optimistic. To explore the novel antimalarial natural products from plant,thirty plants from West Yunnan were extracted by reflux method with75% ethanol and water,successively. Then the antimalarial activities of the samples were tested by β-hematin formation inhibition assay. As a result,Mussaenda pubescens,Rhodobryum roseum,Glycyrrhiza pallidiflora and other 19 testing samples showed β-hematin formation inhibition activity in different degrees,which came from 17 families and 19 genera. Among the active samples,the water extracts of Woodfordia fruticosa,Ardisia elliptica and Hedychium coronarium,as well as the ethanol extract of Geranium refractum,showed significant inhibition activities with the IC_(50) values of796.0,951.0,1 033.0,1 388.9 μg·m L~(-1),respectively. HPLC analysis of Woodfordia fruticosa and Ardisia elliptica indicated that their active components should be phenolic constituents.
Malaria is a parasitic disease that seriously endangers human health. According to the world health organization,hundreds of thousands of people died due to malaria each year. Although the prevention and treatment of malaria in China has made great progress,the local malaria cases still exist in the border areas of Yunnan and Nyingchi of Tibet,China. In addition to the special geographical locations of Tibet and Yunnan,China shares borders with neighboring countries with high incidence of malaria,and the border residents have frequent contacts,so the source of infection cannot be eliminated. Therefore,the situation of malaria prevention and control in China is still not optimistic. To explore the novel antimalarial natural products from plant,thirty plants from West Yunnan were extracted by reflux method with75% ethanol and water,successively. Then the antimalarial activities of the samples were tested by β-hematin formation inhibition assay. As a result,Mussaenda pubescens,Rhodobryum roseum,Glycyrrhiza pallidiflora and other 19 testing samples showed β-hematin formation inhibition activity in different degrees,which came from 17 families and 19 genera. Among the active samples,the water extracts of Woodfordia fruticosa,Ardisia elliptica and Hedychium coronarium,as well as the ethanol extract of Geranium refractum,showed significant inhibition activities with the IC_(50) values of796.0,951.0,1 033.0,1 388.9 μg·m L~(-1),respectively. HPLC analysis of Woodfordia fruticosa and Ardisia elliptica indicated that their active components should be phenolic constituents.
引文
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XU YJ,PIETERS L,2013.Recent developments in antimalarial natural products isolated from medicinal plants[J].MiniRev Med Chem,13(7):1056-1072.
ZHANG L,FENG J,ZHANG SS,et al.,2017.Malaria situation in the People's Republic of China in 2016[J].Chin J Parasitol Parasit Dis Dec,35(6):515-519.[张丽,丰俊,张少森,等,2017.2016年全国疟疾疫情分析[J].中国寄生虫学与寄生虫病杂志,35(6):515-519.]
BIRKETT AJ,MOORTHY VS,LOUCQ C,et al.,2013.Malaria vaccine R&D in the decade of vaccines:Breakthroughs,challenges and opportunities[J].Vaccine,31(Suppl.2):B233-B243.
CHONG CR,SULLIVAN JR DJ,2003.Inhibition of heme crystal growth by antimalarials and other compounds:Implications for drug discovery[J].Biochem Pharmacol,66(11):2201-2212.
DAS P K,GOSWAMI S,CHINNIAH A,et al.,2007.Woodfordia fruticosa:Traditional uses and recent findings[J].JEthnopharmacol,110(2):189-199.
IMWONG M,SUWANNASIN K,KUNASOL C,et al.,2017.The spread of artemisinin-resistant Plasmodium falciparumin the Greater Mekong subregion:A molecular epidemiology observational study[J].Lancet Infect Dis,17(5):491-497.
JAMPILEK J,2017.Design of antimalarial agents based on natural products[J].Curr Org Chem,21(18):1824-1846.
KAYSER O,KIDERLEN AF,CROFT SL,2002.Natural products as potential antiparasitic drugs[J].Stud Nat Prod Chem,26(Part G):779-848.
MATUSCHEWSKI K,2017.Vaccines against malaria-still a long way to go[J].Febs J,284(16):2560-2568.
MISHRA S,AERI V,2017.Biotransformation of lignan glycoside to its aglycone by Woodfordia fruticosa flowers:Quantification of compounds using a validated HPTLCmethod[J].Pharm Biol,55(1):360.
MOJAB F,2012.Antimalarial natural products:A review[J].Avicenna J Phytomed,2(2):52-62.
OKUDA T,YOSHIDA T,HATANO T,et al.,2006.Fractionation of pharmacologically active plant polyphenols by centrifugal partition chromatography[J].J Liq Chromatogr,13(18):3637-3650.
ORJIH A,BANYAL H,CHEVLI R,et al.,1981.Hemin lyses malaria parasites[J].Science,214(4521):667-669.
PAGOLA S,STEPHENS PW,BOHLE DS,et al.,2000.The structure of malaria pigmentβ-haematin[J].Nature,404(6775):307-310.
POHLIT AM,LIMA RBS,FRAUSIN G,et al.,2013.Amazonian plant natural products:Perspectives for discovery of new antimalarial drug leads[J].Molecules,18(8):9219-9240.
PRICE RN,VON SEIDLEIN L,VALECHA N,et al.,2014.Global extent of chloroquine-resistant Plasmodium vivax:A systematic review and meta-analysis[J].Lancet Infect Dis,14(10):982-991.
SLATER AFG,SWIGGARD WJ,ORTON BR,et al.,1991.An iron-carboxylate bond links the heme units of malaria pigment[J].Proc Natl Acad Sci USA,88(2):325-329.
VANGAPANDU S,JAIN M,KAUR K,et al.,2007.Recent advances in antimalarial drug development[J].Med Res Rev,27(1):65-107.
WORLD HEALTH ORGANIZATION,2010.Guidelines for the treatment of malaria:2nd ed[S].Geneva:World Health Organization.
WORLD HEALTH ORGANIZATION,2015.Guidelines for the treatment of malaria:3rd ed[S].Geneva:World Health Organization.
WORLD HEALTH ORGANIZATION,2017a.World Malaria Report 2017[R].Geneva:World Health Organization.
WORLD HEALTH ORGANIZATION,2017b.Artemisinin and artemisinin-based combination therapy resistance[R].Geneva:World Health Organization.
XIAO CJ,DONG X,HAN BY,et al.,2016.Antimalarial activity of Isodon yuennanensis[J].Chin Pharm J,51(8):612-615.[肖朝江,董相,韩冰洋,等,2016.药用植物不育红抗疟活性研究[J].中国药学杂志,51(8):612-615.]
XIAO CJ,XU W,LIU ZQ,et al.,2014.Evaluation of the antimalarial activity of 25 herbal medicines from West Yunnan[J].J Pathog Biol,9(6):542-545.[肖朝江,徐伟,刘子琦,等,2014.滇西地区25种药用植物抗疟活性研究[J].中国病原生物学杂志,9(6):542-545.]
XU YJ,PIETERS L,2013.Recent developments in antimalarial natural products isolated from medicinal plants[J].MiniRev Med Chem,13(7):1056-1072.
ZHANG L,FENG J,ZHANG SS,et al.,2017.Malaria situation in the People's Republic of China in 2016[J].Chin J Parasitol Parasit Dis Dec,35(6):515-519.[张丽,丰俊,张少森,等,2017.2016年全国疟疾疫情分析[J].中国寄生虫学与寄生虫病杂志,35(6):515-519.]