Magnolin Mitigates Skin Ageing Through the CXCL10/p38 Signalling Pathway

ABSTRACT Skin ageing accelerates systemic ageing and impairs the body's disease resistance. Inflammaging is a significant contributor to skin ageing. However, the mechanism by which inflammatory factors contribute to skin ageing remains unclear. We conducted screenings and identified CXC motif chemokine ligand 10 ( CXCL10 ) as an inducer of skin ageing, which can be effectively inhibited by magnolin extracted from Magnolia biondii flower. Our results show that CXCL10 not only enhances beta‐galactosidase (β‐gal) activity but also upregulates the expression of p21/p16, along with matrix metalloproteinases ( MMP1 , MMP9 and MMP10 ), through activation of the C‐X‐C motif chemokine receptor 3 ( CXCR3 ) in human primary fibroblasts. These findings suggest that CXCL10 drives skin ageing by inducing cellular senescence and extracellular matrix degradation. Importantly, treatment with magnolin significantly mitigates skin ageing phenotypes induced by CXCL10 via the p38 signalling pathway. Furthermore, our study demonstrates that magnolin significantly mitigates UV ‐induced skin ageing in ex vivo human skin samples as well as on human facial skin. This study provides insight into the role of chemokine CXCL10 in promoting inflammaging and proposes an innovative approach for preventing and treating skin ageing.