1. Discovery of Coumarins from Zanthoxylum dimorphophyllum var. spinifolium as and Their Potential against Rheumatoid Arthritis.
- Author
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Du, Caixia, Li, Xingyu, Chen, Junlei, Luo, Lili, Yuan, Chunmao, Yang, Jue, Hao, Xiaojiang, and Gu, Wei
- Subjects
CHINESE medicine ,RHEUMATOID arthritis ,NUCLEAR magnetic resonance spectroscopy ,MOLECULAR docking ,CLINICAL medicine - Abstract
In the present study, a series of coumarins, including eight undescribed bis-isoprenylated ones Spinifoliumin A-H, were isolated and identified from the aerial parts of Zanthoxylum dimorphophyllum var. spinifolium (ZDS), a plant revered in traditional Chinese medicine, particularly for treating rheumatoid arthritis (RA). The structures of the compounds were elucidated using 1D and 2D NMR spectroscopy, complemented by ECD, [Rh
2 (OCOCF3 )4 ]-induced ECD, Mo2 (OAc)4 induced ECD, IR, and HR-ESI-MS mass spectrometry. A network pharmacology approach allowed for predicting their anti-RA mechanisms and identifying the MAPK and PI3K-Akt signaling pathways, with EGFR as a critical gene target. A CCK-8 method was used to evaluate the inhibition activities on HFLS-RA cells of these compounds. The results demonstrated that Spinifoliumin A, B, and D-H are effective at preventing the abnormal proliferation of LPS-induced HFLS-RA cells. The results showed that compounds Spinifoliumin A, D, and G can significantly suppress the levels of IL-1β, IL-6, and TNF-α. Moreover, molecular docking methods were utilized to confirm the high affinity between Spinifoliumin A, D, and G and EGFR, SRC, and JUN, which were consistent with the results of network pharmacology. This study provides basic scientific evidence to support ZDS's traditional use and potential clinical application. [ABSTRACT FROM AUTHOR]- Published
- 2024
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