RRC ID 81179
Author Mao L, Liu L, Li J, Yang X, Xu X, Liu M, Zhang Y, Wei W, Chen J.
Title Ginsenoside compound K plays an anti-inflammatory effect without inducing glucose metabolism disorder in adjuvant-induced arthritis rats.
Journal Food Funct
Abstract Ginsenoside compound K (GCK) possesses a glucocorticoid (GC)-like structure and functions as an agonist of the glucocorticoid receptor (GR), thereby exerting anti-inflammatory effects through GR activation. However, it remains unclear whether GCK leads to hyperglycemia, which is a known adverse reaction associated with classical GCs. In this study, we have successfully demonstrated that GCK exerts its anti-inflammatory effects in a rat model of adjuvant arthritis without impacting gluconeogenesis and pentose phosphate pathways, thus avoiding any glucose metabolism disorders. By employing the GR mutant plasmid, we have identified the binding site between GCK and GR as GRM560T, which differs from the binding site shared by dexamethasone (DEX) and GR. Notably, compared to DEX, GCK induces distinct levels of phosphorylation at S211 on GR upon binding to activate steroid receptor coactivator 1 (SRC1)-a co-factor responsible for mediating anti-inflammatory effects-while not engaging peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α)-an associated coactivator involved in gluconeogenesis.
Volume 15(12)
Pages 6475-6487
Published 2024-6-17
DOI 10.1039/d4fo01460j
PMID 38804652
MeSH Animals Anti-Inflammatory Agents* / pharmacology Arthritis, Experimental* / drug therapy Arthritis, Experimental* / metabolism Dexamethasone / pharmacology Ginsenosides* / pharmacology Gluconeogenesis / drug effects Glucose / metabolism Humans Male Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / genetics Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / metabolism Rats Rats, Sprague-Dawley* Receptors, Glucocorticoid* / metabolism
Resource
Human and Animal Cells MH7A(RCB1512)