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Panax notoginseng saponins (PNS)alleviates rheumatoid arthritis by regulating HIF-1α/PKM2-mediated glycolysis to inhibit Th17 differentiation.

Created on 10 Jul 2026

Authors

Yujie Bao, Shuoyu Chen, Yu Ge, Qiaoyu Zhang, Furong Wang, Baoping Jiang, Lingling Zhou

Published in

Molecular biology reports. Volume 53. Issue 1. Jul 10, 2026. Epub Jul 10, 2026.

Abstract

To assess Panax notoginseng saponins(PNS)'s therapeutic potential against RA and its modulation of Th17 differentiation, specifically the in vitro mechanism by which PNS inhibits Th17 cell glycolysis via the HIF-1α pathway.
Collagen-induced arthritis (CIA) mouse model was established by immunization with type II collagen. CIA mice were randomly divided into control, model, and PNS (100 mg/kg) treatment groups. Network pharmacology was employed to identify PNS active components and RA-related targets; protein-protein interaction (PPI) network construction and pathway enrichment analysis were used to predict core targets. Naive CD4⁺T cells were induced to differentiate into Th17 cells with interleukin (IL)-6, IL-23, and transforming growth factor-β (TGF-β), and treated with PNS at concentrations of 5, 10, and 20 µg/mL). Th17 differentiation, IL-17 A secretion, and pathway-related molecules were detected by flow cytometry, ELISA, RT-qPCR, and immunoblotting. Compound 3 K and DFOM validated the mechanism.
PNS attenuated CIA severity (reduced hind paw swelling, arthritis scores, improved body weight, alleviated pathology). KEGG linked Th17 differentiation, PKM2, HIF-1α to PNS's anti-RA effects. PNS reduced Th17 ratios, inhibited PKM2/HIF-1α expression, suppressed PKM2-mediated glycolysis, and reversed HIF-1α hyperactivation in Th17 cells.
PNS relieves CIA by inhibiting Th17 differentiation via suppressing HIF-1α-mediated PKM2 expression and glycolysis-dependent Th17 differentiation.

PMID:
42429989
Bibliographic data and abstract were imported from PubMed on 10 Jul 2026.

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