Gastrodin Ameliorates the Inflammation, Oxidative Stress, and Extracellular Matrix Degradation of IL-1β-Mediated Fibroblast-Like Synoviocytes via Suppressing the Gremlin-1/NF-κB Pathway

Synovial inflammation plays a crucial role in osteoarthritis (OA). Gastrodin (GAS), an active ingredient derived from the Gastrodia elata Blume rhizome, possesses antioxidant and anti-inflammatory pharmacological effects. This research aimed to evaluate the function and molecular mechanism of GAS on...

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Veröffentlicht in:Discovery medicine 2024-07, Vol.36 (186), p.1441
Hauptverfasser: Hu, Yong, Li, Ming, Chen, Xiao-Yan, Huang, Chun-Hang, Cao, Hui-Yuan, Wang, Guang-Ji, Du, Xiu-Fan
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Sprache:eng
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Zusammenfassung:Synovial inflammation plays a crucial role in osteoarthritis (OA). Gastrodin (GAS), an active ingredient derived from the Gastrodia elata Blume rhizome, possesses antioxidant and anti-inflammatory pharmacological effects. This research aimed to evaluate the function and molecular mechanism of GAS on human fibroblast-like synoviocytes of osteoarthritis (HFLS-OA) induced by interleukin (IL)-1β. The impact of GAS on the viability of IL-1β-treated HFLS-OA cells was assessed using the cell counting kit-8 (CCK-8). Quantitative real-time reverse transcription PCR (qRT-PCR) was employed to detect changes in , , monocyte chemotactic protein-1 ( ), tumor necrosis factor ( )-α, and mRNA expression in each group. Corresponding kits were utilized to measure the catalase (CAT) and superoxide dismutase (SOD) activities, as well as the nitric oxide (NO) level. Western blot analysis was conducted to examine the expression of extracellular matrix degradation-associated proteins and nuclear factor kappa-B (NF-κB) pathway-correlated proteins in each group. GAS significantly promoted the proliferation of IL-1β-induced HFLS-OA cells and concurrently down-regulated mRNA expression ( < 0.05). Through the down-regulation of expression, GAS exhibited the following effects: decreased , , and mRNA expression, as well as NO levels ( < 0.05); increased SOD and CAT activities ( < 0.05); down-regulated matrix metallopeptidase 13 (MMP-13) and MMP-1 protein expression levels ( < 0.01); and up-regulated collagen II protein expression level ( < 0.01) in IL-1β-treated HFLS-OA cells. Additionally, GAS decreased phospho-inhibitory kappa B (p-IκB)/IκB, phospho-inhibitory kappa B kinase (p-IKK)/IKK, and p-p65/p65 ratios in IL-1β-induced HFLS-OA cells by inhibiting Gremlin-1 expression ( < 0.01). GAS demonstrates a positive impact on inflammation, oxidative stress, and extracellular matrix degradation in IL-1β-mediated HFLS-OA cells. This effect is achieved by suppressing Gremlin-1 expression and reducing NF-κB pathway activity.
ISSN:1539-6509
1944-7930
1944-7930
DOI:10.24976/Discov.Med.202436186.134