Department of Cell Biology, College of Life Science and Technology, Jinan University, Guangzhou, China.
Guangdong Provincial Biotechnology Drug & Engineering Technology Research Center, Guangzhou, China.
BMC Complement Med Ther. 2024 Jul 11;24(1):264. doi: 10.1186/s12906-024-04578-z.
Artemisia argyi is a traditional herbal medicine belonging to the genus Artemisia that plays an important role in suppressing inflammation. However, the chemical constituents and underlying mechanisms of its therapeutic potential in neuroinflammation are still incompletely understood, and warrant further investigation.
Several column chromatography were employed to isolate and purify chemical constituents from Artemisia argyi, and modern spectroscopy techniques were used to elucidate their chemical structures. The screening of monomeric compounds with nitric oxide inhibition led to the identification of the most effective bioactive compound, which was subsequently confirmed for its anti-inflammatory capability through qRT‒PCR. Predictions of compound-target interactions were made using the PharmMapper webserver and the TargetNet database, and an integrative protein-protein interaction network was constructed by intersecting the predicted targets with neuroinflammation-related targets. Topological analysis was performed to identify core targets, and molecular docking and molecular dynamics simulations were utilized to validate the findings. The result of the molecular simulations was experimentally validated through drug affinity responsive target stability (DARTS) and Western blot experiments.
Seventeen sesquiterpenoids, including fifteen known sesquiterpenoids and two newly discovered guaiane-type sesquiterpenoids (argyinolide S and argyinolide T) were isolated from Artemisia argyi. Bioactivity screening revealed that argyinolide S (AS) possessed the most potent anti-inflammatory activity. However, argyinolide T (AT) showed weak anti-inflammatory activity, so AS was the target compound for further study. AS may regulate neuroinflammation through its modulation of eleven core targets: protein kinase B 1 (AKT1), epidermal growth factor receptor (EGFR), proto-oncogene tyrosine-protein Kinase (FYN), Janus Kinase (JAK) 1, mitogen-activated protein (MAP) Kinase 1,8 and 14, matrix metalloproteinase 9 (MMP9), ras-related C3 botulinum toxin substrate 1 (RAC1), nuclear factor kappa-B p65 (RELA), and retinoid X receptor alpha (RXRA). Molecular dynamics simulations and DARTS experiments confirmed the stable binding of AS to JAK1, and Western blot experiments demonstrated the ability of AS to inhibit the phosphorylation of downstream Signal transducer and activator of transcription 3 (STAT3) mediated by JAK1.
The sesquiterpenoid compounds isolated from Artemisia argyi, exhibit significant inhibitory effects on inflammation in C57BL/6 murine microglia cells (BV-2). Among these compounds, AS, a newly discovered guaiane-type sesquiterpenoid in Artemisia argyi, has been demonstrated to effectively inhibit the occurrence of neuroinflammation by targeting JAK1.
艾草是菊科蒿属的一种传统草药，在抑制炎症方面发挥着重要作用。然而，其在神经炎症中的治疗潜力的化学成分和潜在机制仍不完全清楚，需要进一步研究。
采用多种柱层析法从艾草中分离和纯化化学成分，并运用现代光谱技术阐明其化学结构。通过对具有抑制一氧化氮生成活性的单体化合物进行筛选，鉴定出最有效的生物活性化合物，随后通过 qRT-PCR 验证其抗炎能力。使用 PharmMapper 网络服务器和 TargetNet 数据库预测化合物-靶标相互作用，并通过 intersect 将预测的靶标与神经炎症相关靶标相交，构建整合的蛋白质-蛋白质相互作用网络。进行拓扑分析以确定核心靶标，并通过分子对接和分子动力学模拟验证发现。通过药物亲和反应靶标稳定性（DARTS）和 Western blot 实验对分子模拟的结果进行实验验证。
从艾草中分离得到 17 种倍半萜类化合物，包括 15 种已知的倍半萜类化合物和 2 种新发现的愈创木烷型倍半萜类化合物（argyinolide S 和 argyinolide T）。生物活性筛选表明，argyinolide S（AS）具有最强的抗炎活性。然而，argyinolide T（AT）表现出较弱的抗炎活性，因此 AS 是进一步研究的目标化合物。AS 可能通过调节十一个核心靶标来调节神经炎症：蛋白激酶 B1（AKT1）、表皮生长因子受体（EGFR）、原癌基因酪氨酸蛋白激酶（FYN）、Janus 激酶（JAK）1、丝裂原激活蛋白（MAP）激酶 1、8 和 14、基质金属蛋白酶 9（MMP9）、ras 相关 C3 肉毒杆菌毒素底物 1（RAC1）、核因子 kappa-B p65（RELA）和视黄醇 X 受体 alpha（RXRA）。分子动力学模拟和 DARTS 实验证实了 AS 与 JAK1 的稳定结合，Western blot 实验表明 AS 能够抑制 JAK1 介导的下游信号转导和转录激活因子 3（STAT3）的磷酸化。
从艾草中分离得到的倍半萜类化合物对 C57BL/6 小鼠小胶质细胞（BV-2）中的炎症有显著的抑制作用。在这些化合物中，AS，一种在艾草中发现的新的愈创木烷型倍半萜类化合物，已被证明通过靶向 JAK1 有效抑制神经炎症的发生。
