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DOI: 10.1055/a-2706-8264
Active Components and Multi-target Mechanism of Tibetan Sinopodophyllum hexandrum Medicine Against Rheumatoid Arthritis Using a CFA-induced Arthritis Rat Model
Authors
This work was financially supported by the Jiangxi Province Key Laboratory of Precision Cell Therapy (No. 2024SSY06241), the General Program of Jiangxi Provincial Natural Science Foundation (No. 20224BAB206105), the Science and Technology Plan Project of Jiangxi Administration of Traditional Chinese Medicine (No. 2023A0362), the Science and Technology Plan Project of Jiangxi Provincial Health Commission (No. 202310536), and the National Natural Science Foundation Incubation Project of the Second Affiliated Hospital of Nanchang University (No. 2022YNFY12039).

Abstract
Sinopodophyllum hexandrum (“Taoerqi”) is a traditional Tibetan medicine used for treating inflammation and arthralgia, but its therapeutic basis against rheumatoid arthritis (RA) remains unclear. This study aimed to identify its active anti-RA fraction, analyse its chemical composition, and explore its mechanisms of action. Using a CFA-induced arthritis rat model, the dichloromethane fraction of S. hexandrum (SHD) was evaluated for anti-RA activity. UHPLC-Q-TOF-MS/MS identified 57 compounds, mainly prenylated flavonoids and arylnaphthalene lignans. Network pharmacology predicted their targets, and in vitro assays on TNF-α-induced fibroblast-like synoviocytes confirmed the anti-RA effects of 15 isolates. Enzyme inhibition, molecular docking, surface plasmon resonance, and Western blot validated their interactions with TNF-α and JAK1. Oral administration of SHD significantly reduced paw swelling and neutrophil infiltration in RA rats. These findings suggest that prenylated flavonoids and arylnaphthalene lignans are key active components exerting anti-RA effects, respectively, via TNF-α and JAK1 inhibition, highlighting their potential for further drug development.
Keywords
Sinopodophyllum hexandrum - prenylated flavonoids - arylnaphthalene lignans - rheumatoid arthritis - TNF-α - JAK1 - BerberidaceaeSupporting Information
- Ergänzendes Material (PDF)
Full spectral interpretations of the isolated compounds 1–15 (including MS, ¹H, and ¹³C NMR spectra as shown in Fig. 2S–31S), activity assays for TP53, AKT1, TLR4, SRC, and GAPDH, Fig. 1S (pharmacology network of SHD), Table 1S (identification of chemical components in SHD by UHPLC-ESI-QTOF-MS), Table 2S (IC50 values for the inhibitory effects of SHD, compound 2, and compound 11 on different targets), and Table 3S (primer sequences) are available as Supporting Information.
Publikationsverlauf
Eingereicht: 22. März 2025
Angenommen nach Revision: 15. September 2025
Artikel online veröffentlicht:
20. Oktober 2025
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