Artemisinine is a sesquiterpene lactone antimalarial drug extracted from the plant Artemisia annua[1]. Artemisinine interferes with the biological membrane structure of the malaria parasite, particularly the mitochondrial and endoplasmic reticulum membranes, leading to the death of the parasite and thus is widely used in the treatment of malaria[2]. Artemisinine has also been studied for its potential applications in treating various diseases, including antiviral activity, cancer, metabolic syndrome, and fibrosis[3][4].
In vitro, pretreatment of PC12 cells with Artemisinine(3.125–100μM; 1h) concentration-dependently inhibited Aβ25–35-induced cytotoxicity, reduced the release of lactate dehydrogenase (LDH), decreased intracellular reactive oxygen species (ROS) generation, restored mitochondrial membrane potential (△ψm), and inhibited the increase in caspase 3/7 activity associated with apoptosis[5]. Pretreatment of HT-22 cells with Artemisinine(25μM; 12h) significantly reduced glutamate-induced cell death and activated Akt/Bcl-2 signaling[6].
In vivo, treatment of STZ-induced T2DM mice with Artemisinine (40mg/kg/day; i.p.; 4 weeks) significantly reversed diabetic cognitive impairments, decreased the levels of ROS, MDA, and Fe²⁺ in the hippocampus, increased the levels of Nrf2, HO-1, GPX4, and GSH, and alleviated neuronal ferroptosis and neuronal loss in the hippocampal CA1 region[7]. Artemisinine (10mg/kg/day; i.p.; 7 days) reversed ischemic stroke-induced neuronal pyroptosis in photochemically induced thrombosis (PIT) model mice, decreased the levels of IL-1β and IL-18 in serum, and downregulated the expression of key proteins NLRP3, ASC-1, Caspase-1, and TXNIP in mouse brain tissue[8].
References:
[1] Tu Y. Artemisinin-A Gift from Traditional Chinese Medicine to the World (Nobel Lecture). Angew Chem Int Ed Engl. 2016;55(35):10210-10226.
[2] Ribbiso KA, Heller LE, Taye A, Julian E, Willems AV, Roepe PD. Artemisinin-Based Drugs Target the Plasmodium falciparum Heme Detoxification Pathway. Antimicrob Agents Chemother. 2021;65(4):e02137-20.
[3] Augustin Y, Staines HM, Krishna S. Artemisinins as a novel anti-cancer therapy: Targeting a global cancer pandemic through drug repurposing. Pharmacol Ther. 2020;216:107706.
[4] Addissouky T A .Artemisinin and its derivatives throughout the therapeutic mechanisms and clinical potential.Discover Chemistry. 2025, 2(1):1-16.
[5] Zeng Z, Xu J, Zheng W. Artemisinin protects PC12 cells against β-amyloid-induced apoptosis through activation of the ERK1/2 signaling pathway. Redox Biol. 2017;12:625-633.
[6] Lin SP, Li W, Winters A, Liu R, Yang SH. Artemisinin Prevents Glutamate-Induced Neuronal Cell Death Via Akt Pathway Activation. Front Cell Neurosci. 2018;12:108.
[7] Wang B, Zhu S, Guo M, et al. Artemisinin ameliorates cognitive decline by inhibiting hippocampal neuronal ferroptosis via Nrf2 activation in T2DM mice. Mol Med. 2024;30(1):35.
[8] Wang Y, Yuan H, Shen D, et al. Artemisinin attenuated ischemic stroke induced pyroptosis by inhibiting ROS/TXNIP/NLRP3/Caspase-1 signaling pathway. Biomed Pharmacother. 2024;177:116894.
Artemisinine是一种从青蒿植物（Artemisia annua）中提取的倍半萜内酯类抗疟药[1]。Artemisinine通过干扰疟原虫的生物膜结构，特别是线粒体和内质网膜，导致疟原虫死亡，因此被广泛用于疟疾治疗[2]。Artemisinine还被研究用于抗病毒、抗癌、代谢综合征、纤维化等多种疾病的治疗[3][4]。
在体外实验中，用Artemisinine（3.125–100μM；1小时）预处理PC12细胞，浓度依赖性地抑制了Aβ25–35诱导的细胞毒性，减少了乳酸脱氢酶（LDH）的释放，降低了细胞内活性氧（ROS）的生成，恢复了线粒体膜电位（△ψm），并抑制了与凋亡相关的caspase 3/7活性的增加[5]。用Artemisinine（25μM；12小时）预处理HT-22细胞，显著减少了谷氨酸诱导的细胞死亡，并激活了Akt/Bcl-2信号通路[6]。
在体内实验中，用Artemisinine（40mg/kg/天；腹腔注射；4周）处理STZ诱导的2型糖尿病（T2DM）小鼠，显著改善了糖尿病引起的认知功能障碍，降低了海马体中ROS、丙二醛（MDA）和Fe²⁺的水平，增加了Nrf2、HO-1、GPX4和GSH的水平，并减轻了海马体CA1区的神经元铁死亡和神经元丢失[7]。Artemisinine（10mg/kg/天；腹腔注射；7天）逆转了光化学诱导血栓（PIT）模型小鼠中缺血性中风诱导的神经元焦亡，降低了血清中IL-1β和IL-18的水平，并下调了小鼠脑组织中关键蛋白NLRP3、ASC-1、Caspase-1和TXNIP的表达[8]。