Glycyl-L-histidyl-L-lysine-Cu2<sup>+</sup> (GHK-Cu) Attenuates CuSO<sub>4</sub> or LPS induced-inflammation in Zebrafish larvae model.
This study investigated the anti-inflammatory and antioxidant properties of the bioactive tripeptide complex GHK-Cu (Glycyl-L-histidyl-L-lysine-Cu²⁺) using zebrafish larvae as an in vivo model. Researchers induced acute inflammation in larvae using either copper sulfate (CuSO₄) or lipopolysaccharide (LPS) and then assessed the effects of GHK-Cu treatment. According to the study, GHK-Cu notably reduced the migration of neutrophils and macrophages to sites of inflammation. It also suppressed the gene expression of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) while upregulating the anti-inflammatory cytokine IL-10. The compound was further reported to reduce markers of oxidative stress, including nitric oxide (NO) and reactive oxygen species (ROS), and to improve superoxide dismutase (SOD) activity. Pathway analysis suggested that GHK-Cu's effects may be mediated in part through downregulation of the JAK1 signaling pathway. The authors propose that these findings provide a theoretical basis for the use of GHK-Cu as a functional cosmetic ingredient. Key limitations include the use of a non-mammalian animal model and the absence of human or cell-culture mechanistic data, meaning clinical translation remains unestablished.
Why this grade: All experiments were conducted exclusively in zebrafish (Danio rerio) larvae with no human subjects, clinical data, or mammalian models, limiting direct extrapolation to human biology.
Inflammation serves as a basic defense mechanism against both internal and external threats, while the unresolved or excessive inflammation can lead to irreversible tissue damage. Glycyl-L-histidyl-L-lysine-Cu 2+ (GHK-Cu), a bioactive tripeptide complex known for its anti-aging and tissue repair properties, is extensively utilized in dermatological and hair care formulations. However, the role of GHK-Cu in regulating inflammation is less known. In this study, we explored the anti-inflammatory effects of GHK-Cu against the acute inflammation induced by copper sulfate (CuSO 4 ) and lipopolysaccharide (LPS) in zebrafish larvae. GHK-Cu notably decreased the migration of neutrophils and macrophages, suppressed the expression of pro-inflammatory cytokines (tnf-a, il-1β, il6) and increased the expression of the anti-inflammatory cytokine il-10. Moreover, GHK-Cu mitigated oxidative stress by reducing levels of nitric oxide (NO) and reactive oxygen species (ROS), and improved superoxide dismutase (SOD) activity. Furthermore, pathway analysis revealed that GHK-Cu administration downregulated the JAK1 pathway. In summary, this study highlights the dual role of GHK-Cu in both anti-inflammatory and anti-oxidant properties, which provides the theoretical evidences supporting its addition as a functional cosmetic ingredient.
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