Glucocorticoid receptors involved in ginsenoside compound K ameliorate adjuvant arthritis by inhibiting the glycolysis of fibroblast-like synoviocytes via the NF-kappa B/HIF-1 alpha pathway

Context: Ginsenoside metabolite compound K (CK) is an active metabolite produced by ginsenosides in vivo that has an anti-arthritic effect related to the glucocorticoid receptor (GR). However, the potential mechanisms of CK remain unclear. Objective: This study explores the role and potential mechanisms of CK in vivo and in vitro. Materials and methods: Adjuvant arthritis (AA) model was induced in Sprague-Dawley (SD) rats; the rats were randomly divided into four groups (n = 10): normal, AA, CK (80mg/kg), and dexamethasone (Dex) group (1 mg/kg). From day 15, rats were treated with CK (once a day, i.g.) and Dex (once every 3 days, i.p.) for 18 days. To further verify the mechanism of CK, fibroblast-like synoviocytes (FLS) were stimulated by tumour necrosis factor alpha (TNF-alpha) to establish an inflammatory model in vitro. Results: CK (80mg/kg) reduced paw swelling (52%) and arthritis global assessment (31%) compared to that in AA rats. In addition, CK (80 mg/kg) suppressed GLUT1 (38%), HK2 (50%), and PKM2 (56%) levels compared with those in AA FLS. However, the effects of CK (30 mu M) on these events were weakened or enhanced after GR knockdown or overexpression in FLS stimulated by TNF-alpha (30 ng/mL). CK (80 mg/kg) also downregulated the expression of P65 (61%), p-I kappa B (92%), and HIF-1 alpha (59%). Discussion and conclusions: The inhibition of CK on glycolysis and the NF-kappa B/HIF-1 alpha pathway is potentially mediated through activating GR. These findings provide experimental evidence for elucidating the molecular mechanism of CK in treating rheumatoid arthritis (RA).

Automated summary

This study investigates the role and potential mechanisms of ginsenoside metabolite compound K (CK) in the treatment of rheumatoid arthritis (RA). The results demonstrate that CK can reduce arthritis symptoms and inhibit inflammation-related genes and pathways. These findings contribute to the understanding of the molecular mechanism of CK in treating RA.