Gao Jindong, Lei Kuang, Zhang Mengdi, Yin Jinhua, Hu Changmin
College of Animal Science and Technology, Tarim University, Alar 843300, China.
Key Laboratory of Tarim Animal Husbandry Science and Technology, Xinjiang Production and Construction Corps, Alar 843300, China.
Int J Mol Sci. 2025 May 9;26(10):4531. doi: 10.3390/ijms26104531.
Dihydroartemisinin (DHA) is a bioactive phytopharmaceutical with diverse pharmacological potential, predominantly because of its established antiplasmodial efficacy. Here, we investigated the effects of DHA on metabolic homeostasis in Madin-Darby bovine kidney cells in the context of dose-specific adaptation of metabolism and regulation of biochemistry pathway changes. According to our findings, extensive changes in metabolism were revealed by PCA, accounting for a variability of 59.4% to distinguish contrasting metabolic signatures from normal cells. Metabolomic characterization demonstrated 67 constituting metabolites of baseline cellular processes, while 32 and 44 metabolites have demonstrated differential abundance in low- and high-dose treatments, respectively. Impaired metabolism of glycerophospholipid, amino acid, and nucleotide biosynthesis was reported with implications such as regulation of membrane reorganization, nitrogen metabolism, and cellular bioenergetics. Bioindicators of high-volume lysophosphatidylcholine (18:0) and choline phosphate revealed a lipid homeostatic change, in addition to imbalances in glutamic acid and proline levels. Pathway regulation further modulated ABC transporters and arachidonic acid signaling as implications of systemic phytopharmaceutical-modulated reorganization of metabolism. Hence, the study gives mechanistic insight into DHA-initiated modulation of cellular metabolism in MDBK cells, elucidating its status as a cellular metabolism regulator. Findings confirm the potential of DHA as a phytopharmaceutical in modulating diseases of metabolism, further solidifying its relevance in evidence-based traditional herbal remedies and natural compound therapeutics.
双氢青蒿素(DHA)是一种具有多种药理潜力的生物活性植物药,主要因其已确立的抗疟原虫功效。在此,我们在代谢的剂量特异性适应性和生化途径变化调节的背景下,研究了DHA对Madin-Darby牛肾细胞代谢稳态的影响。根据我们的研究结果,主成分分析揭示了代谢的广泛变化,占变异性的59.4%,以区分与正常细胞形成对比的代谢特征。代谢组学表征显示了67种构成基线细胞过程的代谢物,而分别有32种和44种代谢物在低剂量和高剂量处理中表现出丰度差异。据报道,甘油磷脂、氨基酸和核苷酸生物合成的代谢受损,其影响包括膜重组调节、氮代谢和细胞生物能学。大量溶血磷脂酰胆碱(18:0)和磷酸胆碱的生物标志物除了谷氨酸和脯氨酸水平失衡外,还揭示了脂质稳态变化。途径调节进一步调节了ABC转运蛋白和花生四烯酸信号传导,这是系统性植物药调节代谢重组的影响。因此,该研究深入了解了DHA引发的MDBK细胞中细胞代谢调节机制,阐明了其作为细胞代谢调节剂的地位。研究结果证实了DHA作为植物药在调节代谢疾病方面的潜力,进一步巩固了其在循证传统草药和天然化合物治疗中的相关性。