Ounjaijean Sakaewan, Somsak Voravuth
NCD Center of Excellence, Research Institute for Health Sciences, Chiang Mai University, Chiang Mai 50200, Thailand.
School of Allied Health Sciences, Walailak University, Nakhon Si Thammarat 80161, Thailand; Research Excellence Center for Innovation and Health Products, Walailak University, Nakhon Si Thammarat 80161, Thailand.
Parasitol Int. 2020 Jun;76:102088. doi: 10.1016/j.parint.2020.102088. Epub 2020 Feb 20.
Malaria is a global health problem leading to the death of 435,000 cases in tropical and sub-tropical zones. Spread and emergence of increasing resistance to the antimalarial drugs are the major challenges in the control of malaria. Therefore, searching for alternative antimalarial drugs is urgently needed, and combination treatment preferred as an approach to address this. This study aimed to evaluate in vivo antimalarial activity of zingerone (ZN), and its combination with dihydroartemisinin (DHA) against Plasmodium berghei infected mice. ZN was prepared and tested for acute oral toxicity according to the OECD guideline. In vivo antimalarial activity of different doses of ZN and combination with DHA were determined using the 4-day suppression test. The results showed that ZN was found to be safe and no mortality within the observation period, and the lethal dose might be greater than the limited dose of 1000 mg/kg. For in vivo antimalarial test, ZN exhibited significant (p < .05) parasitemia inhibition of 30.65% and 45.75% at the doses of 50 mg/kg and 100 mg/kg, respectively. Moreover, effective dose 50 (ED) of ZN was 29.76 mg/kg. The combination treatment of ZN and DHA at the doses of ED values at the fixed ratio 1:1 was found to present significant (p < .001) antimalarial activity as compared to ZN and DHA treated alone with markedly prolonged mean survival time. Additionally, the combination index (0.83384) revealed the synergistic antimalarial effect. It can be concluded that ZN exerted potent antimalarial activity with no toxicity, and combination treatment with DHA produced the synergistic antimalarial effect.
疟疾是一个全球性的健康问题，在热带和亚热带地区每年导致43.5万例死亡。抗疟药物耐药性的不断传播和出现是疟疾防控的主要挑战。因此，迫切需要寻找替代抗疟药物，联合治疗作为解决这一问题的方法更受青睐。本研究旨在评估姜辣素（ZN）及其与双氢青蒿素（DHA）联合对感染伯氏疟原虫小鼠的体内抗疟活性。ZN按照经合组织指南制备并进行急性口服毒性测试。使用4天抑制试验测定不同剂量的ZN及其与DHA联合的体内抗疟活性。结果表明，ZN被发现是安全的，在观察期内无死亡情况，致死剂量可能大于1000 mg/kg的限量。对于体内抗疟试验，ZN在50 mg/kg和100 mg/kg剂量下分别表现出显著（p < 0.05）的疟原虫血症抑制率，分别为30.65%和45.75%。此外，ZN的半数有效剂量（ED50）为29.76 mg/kg。发现ZN和DHA以固定比例1:1的ED值剂量联合治疗与单独使用ZN和DHA相比，具有显著（p < 0.001）的抗疟活性，平均生存时间明显延长。此外，联合指数（0.83384）显示出协同抗疟作用。可以得出结论，ZN具有强效抗疟活性且无毒性，与DHA联合治疗产生协同抗疟作用。
