Curcumol targets glutaminase 1 to regulate glutamine metabolism and induce senescence of hepatic stellate cells

Introduction: Curcuma is used as an herbal remedy for the treatment of chronic liver diseases, and its main active ingredient is curcumol. This study explored the molecular mechanism of curcumol in regulating glutamine metabolism.Methods: The current investigation used lipopolysaccharide (LPS) to activate hepatic stellate cells (HSCs) and then analyzed the effects of curcumol on glutamine metabolism and cell proliferation. The effects of curcumol on glutaminase 1 (GLS1), senescence-related proteins, and extracellular matrix (ECM) expression were examined by western blotting and reverse transcription-quantitative polymerase chain reaction (RT-PCR). The effect of curcumol on the cell cycle was detected by flow cytometry. Furthermore, after overexpression of GLS1, we observed the effects of curcumol on glutamine metabolism, the expression of related molecules, and the cell cycle.Results: Curcumol significantly inhibited cell proliferation, glutamine metabolism, and GLS1 and ECM expression, and also significantly promoted cell senescence. With GLS1 overexpression, the inhibitory effects of curcumol on glutamine metabolism and on promoting cell senescence were rescued.Conclusion: Curcumol targets GLS1, inhibits glutamine metabolism, and induces senescence in HSCs. GLS1 may be an important target for the pharmacological effects of curcumol.