Ali Amatul Hamizah, Sudi Suhaini, Shi-Jing Ng, Hassan Wan Rozianoor Mohd, Basir Rusliza, Agustar Hani Kartini, Embi Noor, Sidek Hasidah Mohd, Latip Jalifah
Department of Chemical Sciences, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, Bangi 43600, Selangor, Malaysia.
Department of Biological Sciences and Biotechnology, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, Bangi 43600, Selangor, Malaysia.
Pharmaceuticals (Basel). 2021 Mar 9;14(3):248. doi: 10.3390/ph14030248.
Although death in malaria is attributed to cerebrovascular blockage and anaemia, overwhelming cytokine production can contribute to the severity of the disease. Therefore, mitigation of dysregulated inflammatory signalling may provide further benefit for malaria treatment. Quercetin (3,3',4',5,7-pentahydroxyflavone) is known to inhibit glycogen synthase kinase-3β (GSK3β), a potent regulator of both pro- and anti-inflammatory effects. Quercetin is therefore a potential therapeutic to modulate the imbalanced cytokine production during malarial infection. Anti-malarial effects of quercetin were evaluated in murine models of severe and cerebral malaria using NK65 and ANKA strains, respectively. Western blotting and analysis of cytokines were carried out to determine the GSK3β-mediated cytokine-modulating effects of quercetin in infected animals. Quercetin (25 mg/kg BW) treatment in NK65-infected animals resulted in 60.7 ± 2.4% suppression of parasitaemia and significantly decreased serum levels of TNF-α and IFN-γ, whilst levels of IL-10 and IL-4 were elevated significantly. Western analysis revealed that pGSK3β (Ser9) increased 2.7-fold in the liver of quercetin-treated NK65-infected animals. Treatment of ANKA-infected mice with quercetin (15 mg/kg BW) increased (2.3-fold) pGSK3β (Ser9) in the brains of infected animals. Quercetin is a potential plant-derived therapeutic for malaria on the basis that it can elicit anti-malarial and GSK3β-mediated cytokine-modulating effects.
尽管疟疾导致的死亡归因于脑血管阻塞和贫血，但细胞因子的过度产生会加重疾病的严重程度。因此，减轻失调的炎症信号传导可能会为疟疾治疗带来更多益处。槲皮素（3,3',4',5,7-五羟基黄酮）已知可抑制糖原合酶激酶-3β（GSK3β），它是促炎和抗炎作用的有效调节因子。因此，槲皮素是一种潜在的治疗药物，可调节疟疾感染期间失衡的细胞因子产生。分别使用NK65和ANKA菌株在重症和脑型疟疾的小鼠模型中评估了槲皮素的抗疟作用。通过蛋白质免疫印迹法和细胞因子分析来确定槲皮素在感染动物中对GSK3β介导的细胞因子调节作用。用槲皮素（25毫克/千克体重）治疗NK65感染的动物，可使寄生虫血症抑制60.7±2.4%，并显著降低血清中TNF-α和IFN-γ的水平，同时IL-10和IL-4的水平显著升高。蛋白质免疫印迹分析显示，在经槲皮素治疗的NK65感染动物的肝脏中，pGSK3β（Ser9）增加了2.7倍。用槲皮素（15毫克/千克体重）治疗ANKA感染的小鼠，可使感染动物大脑中的pGSK3β（Ser9）增加（2.3倍）。基于槲皮素可引发抗疟和GSK3β介导的细胞因子调节作用，它是一种潜在的源自植物的疟疾治疗药物。
