Evaluate the anti-inflammatory activity of the magnolol ester derivative YW and investigate its mechanism of action on chondrocyte senescence
10.19405/j.cnki.issn1000–1492.2026.05 007
- VernacularTitle:评价厚朴酚酯衍生物YW抗炎活性并探究其对软骨细胞衰老的影响机制
- Author:
Haochen XU
1
;
Jie PENG
1
;
Pingting YANG
1
;
Meihua ZHANG
1
;
Weiwen HU
1
;
Xulei WANG
2
;
Wei WEI
1
;
Chun WANG
1
;
Shangxue YAN
1
Author Information
1. Institute of Clinical Pharmacology， School of Pharmaceutical Sciences， Anhui Medical University， Key Laboratory of Anti-inflammatory and Immune Medicines， Ministry of Education，Hefei 230032
2. Experimental Animal Center， Anhui Medical University， Hefei 230032
- Publication Type:Journal Article
- Keywords:
magnolol ester derivatives;
macrophages;
chondrocytes;
anti-inflammation;
senescence
- From:
Acta Universitatis Medicinalis Anhui
2026;61(5):845-854
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo evaluate the anti-inflammatory activity of the novel magnolol ester derivative YW and to investigate its effects on chondrocyte senescence and preliminary mechanisms. MethodsMagnolol and p-methylbenzoic acid were used as raw materials to synthesize the magnolol ester derivative YW （Molecular Formula： C26H24O3， Molecular Weight： 384.17， HPLC Purity >96%） via DCC/DMAP-catalyzed esterification. Cytotoxicity was assessed using the CCK-8 assay. A lipopolysaccharide （LPS）-induced RAW264.7 macrophage activation model and an interleukin-1β （IL-1β）-induced rat primary chondrocyte model were established. The release and mRNA expression of inflammatory factors including nitric oxide （NO）， IL-1β， tumor necrosis factor-alpha （TNF-α）， and IL-6 were detected by enzyme-linked immunosorbent assay （ELISA）， Griess reagent method， and quantitative real-time PCR （RT-qPCR）. The expression of senescence markers such as inducible nitric oxide synthase （iNOS）， pro-interleukin-1β （pro-IL-1β）， lysine acetyltransferase 7 （KAT7）， cyclin-dependent kinase inhibitor 1A （p21）， and cyclin-dependent kinase inhibitor 2A （p16）， as well as proteins related to chondrocyte extracellular matrix synthesis and catabolism， were analyzed by Western blot （WB）. Molecular docking was performed using Discovery Studio 2019 to validate target binding. ResultsYW exhibited no significant cytotoxicity at concentrations ≤20 μmol/L. YW concentration-dependently inhibited LPS-induced macrophage inflammatory cytokine release， significantly downregulated iNOS， Pro-IL-1β protein， and inflammatory cytokine mRNA expression （P<0.01）. YW stably bound to KAT7 protein （binding energy： -94.2 kcal/mol）； YW downregulated KAT7 and aging marker protein expression in naturally aged and IL-1β-induced chondrocyte models （P<0.01）； YW regulated chondrocyte matrix synthesis and catabolic protein expression in IL-1β-induced chondrocytes （P<0.01）. ConclusionYW inhibits macrophage activation and inflammatory cytokine release while downregulating KAT7 and senescence marker protein expression in chondrocytes， thereby blocking chondrocyte senescence.
