Gbedema Stephen Y, Bayor Marcel T, Annan Kofi, Wright Colin W
Department of Pharmaceutics, Faculty of Pharmacy and Pharmaceutical Sciences, College of Health Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana; School of Pharmacy, University of Bradford, Bradford, West Yorkshire BD7 1DP, UK.
Department of Pharmaceutics, Faculty of Pharmacy and Pharmaceutical Sciences, College of Health Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.
J Ethnopharmacol. 2015 Jul 1;169:176-82. doi: 10.1016/j.jep.2015.04.014. Epub 2015 Apr 23.
Plasmodium falciparum drug resistance is a major public health challenge in sub-Sahara Africa. Many people are now resorting to the use of herbs in managing malaria due to the increasing treatment failures with the conventional drugs. In this study the ethanolic extract of Polyalthia longifolia (Sonn) Thw. var. pendula, a variety fondly used in folklore medicine in Ghana was investigated for potential antimalarial drug development.
The ethanolic extract of P. longifolia (Sonn) Thw. var. pendula stem bark was screened against the multidrug resistant, K1 strain of P. falciparum by the parasite lactate dehydrogenase (pLDH) assay and a good antiplasmodial activity (IC50 22.04± 4.23µg/ml) was observed which led to further chromatographic analysis in search for actives.
Bioassay guided fractionation of the extract yielded; three clerodane diterpenes [16-hydroxycleroda-3,13-dien-16,15-olide (1), 16-oxocleroda-3,13E-dien-15-oic acid (2) and 3,16-dihydroxycleroda-4(18),13(14)Z-dien-15,16-olide (3)], a steroid [beta-stigmasterol (4)] and two alkaloids [darienine (5) and stepholidine (6)]. While compounds 4, 5 and 6 exhibited weak antiplasmodial activity (IC50 22-105µg/ml), the clerodane diterpenes exhibited significantly potent (p<0.005) blood schizonticidal activity (IC50: 3-6µg/ml). This is the first report of the antiplasmodial activity of compounds 2 and 3. In combination assay with chloroquine, compounds 1, 2, 3 and 5 antagonized the antiplasmodial activity of chloroquine while 4 and 6 demonstrated a synergistic action.
The potent antiplasmodial activity of the extract of P. longifolia (Sonn) Thw. var. pendula and compounds therein strongly suggests its usefulness as an antimalarial agent and supports its inclusion or exploitation in formulations of herbal remedies for malaria in Ghana.
恶性疟原虫耐药性是撒哈拉以南非洲地区的一项重大公共卫生挑战。由于传统药物治疗失败的情况日益增多，许多人现在 resorting to 使用草药来治疗疟疾。在本研究中，对加纳民间医学中常用的长叶暗罗（Polyalthia longifolia (Sonn) Thw. var. pendula）的乙醇提取物进行了潜在抗疟药物开发的研究。
通过寄生虫乳酸脱氢酶（pLDH）测定法，对长叶暗罗（Polyalthia longifolia (Sonn) Thw. var. pendula）茎皮的乙醇提取物进行了针对多重耐药性恶性疟原虫K1株的筛选，观察到其具有良好的抗疟原虫活性（IC50为22.04±4.23μg/ml），这促使进一步进行色谱分析以寻找活性成分。
提取物的生物测定导向分级分离得到了三种克罗烷二萜[16-羟基克罗达-3,13-二烯-16,15-内酯（1）、16-氧代克罗达-3,13E-二烯-15-酸（2）和3,16-二羟基克罗达-4(18),13(14)Z-二烯-15,16-内酯（3）]、一种甾体[β-谷甾醇（4）]和两种生物碱[达里宁（5）和千金藤啶碱（6）]。虽然化合物4、5和6表现出较弱的抗疟原虫活性（IC50为22 - 105μg/ml），但克罗烷二萜表现出显著强效（p<0.005）的血内裂殖体杀灭活性（IC50：3 - 6μg/ml）。这是化合物2和3抗疟原虫活性的首次报道。在与氯喹的联合测定中，化合物1、2、3和5拮抗氯喹的抗疟原虫活性，而4和6表现出协同作用。
长叶暗罗（Polyalthia longifolia (Sonn) Thw. var. pendula）提取物及其所含化合物的强效抗疟原虫活性强烈表明其作为抗疟剂的有用性，并支持将其纳入或用于加纳疟疾草药配方的开发。
