Cycloastragenol attenuates osteoarthritis by restoring chondrocyte senescence via the NRF2/NF-κB signaling axis

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Osteoarthritis (OA) involves oxidative stress-induced chondrocyte senescence and extracellular matrix (ECM) dysregulation, yet disease-modifying therapies remain elusive. This study investigates the effects of cycloastragenol (CAG), a telomerase-activating triterpenoid from Astragalus membranaceus, on OA progression with a focus on NRF2/NF-κB signaling. In vitro, CAG suppressed oxidative stress-induced senescence in primary rat chondrocytes, evidenced by reduced SA-β-gal positivity, partially restored EdU proliferation, and downregulated senescence related proteins expression. In addition, CAG concurrently attenuated senescence-associated secretory phenotype (SASP) and partially restored ECM homeostasis. Mechanistically, molecular docking analysis suggested a potential interaction between CAG and the Kelch domain of KEAP1. Consistent with this, CAG treatment was associated with NRF2 pathway activation and attenuation of TBHP-induced NF-κB signaling. Importantly, genetic inhibition of NRF2 significantly attenuated the protective effects of CAG, supporting a required role for NRF2 in mediating CAG-induced suppression of oxidative stress and inflammatory signaling. In vivo, intra-articular CAG administration in monosodium iodoacetate (MIA)-induced OA rats reduced cartilage degradation, rescued ECM homeostasis, and enhanced NRF2 activation. Collectively, CAG mitigates the degradati

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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