Activity-guided isolation and identification of antiherpesvirus and antineuroinflammatory active terpenoids from Artemisia vulgaris L. based on the LC-MS/MS molecular network

Liu, Tao; Dai, Minghui; Zhu, Hai; Huang, Yanling; Chen, Jiming; Li, Menghe; Guo, Yuying; Huang, Chen; La, Caiwenjie; Wang, Zui; Wang, Zhiping; Ren, Zhe; Ye, Cuifang; Zheng, Xinglong; Wang, Yifei

doi:10.1016/j.phytochem.2023.113863

Cited by 3 publications

(1 citation statement)

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“…The CD and NMR calculation data were generated using Gaussian 09 software. For the CD calculations, a procedure outlined in a previous study [ 22 ] was followed, where a random conformational search was conducted under the MMFF force field. The optimized stable conformations were further subjected to B3LYP/6-31G (d) level optimization, after screening based on the Boltzmann distribution.…”

Section: Methodsmentioning

confidence: 99%

Isolation and anti-neuroinflammation activity of sesquiterpenoids from Artemisia argyi: computational simulation and experimental verification

La,

Li,

Wang

et al. 2024

BMC Complement Med Ther

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Background 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. Methods 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. Results 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. Conclusions 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.

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Section: Methodsmentioning

confidence: 99%