Synergy of GHK‐Cu and hyaluronic acid on collagen IV upregulation via fibroblast and ex‐vivo skin tests

Abstract Introduction GHK‐Cu and HA are two commonly used skin care ingredients, both of which were reported to enhance collagen synthesis. This work aims to investigate their co‐effect on collagen regulation. Materials and Methods In cell experiments, human dermal fibroblasts were treated by a series of GHK‐Cu and HA combinations, and the expressions of collagen I, IV, and VII were measured by qRT‐PCR. The best formula screened out from cell experiments were further studied by ex‐vivo skin model, and the content of collagen IV was quantified by immunofluorescence method. Results The combination GHK‐Cu and HA was found to promote the generation of collagen I, IV, and VII. Especially, they form a synergy on collagen IV. At the ratio of 1:9, GHK‐Cu and LMW HA deliver the strongest effect to elevate collagen IV synthesis by 25.4 times in cell test and 2.03 times in ex‐vivo skin test. Conclusion The co‐effect of GHK‐Cu and HA was revealed. Their synergy brings an insight to anti‐aging technology: choosing proper molecular weight of HA and managing its ratio with GHK‐Cu could enhance DEJ health via stimulating collagen IV synthesis.