Exploring the beneficial effects of GHK-Cu on an experimental model of colitis and the underlying mechanisms.

Preclinical animal and in vitro study evaluating the therapeutic effects of GHK-Cu in a DSS-induced ulcerative colitis model.

“This study was designed to systematically evaluate the therapeutic potential of GHK-Cu in a dextran sulfate sodium (DSS)-induced murine model of UC, with particular emphasis on elucidating its regulatory effects on the NAD-dependent deacetylase sirtuin-1 (SIRT1)/signal transducer and activator of transcription 3 (STAT3) signaling pathway.”

Male BALB/c mice and mouse cell lines (peritoneal macrophages and colonic epithelial cells).

“Thirty-two male BALB/c mice, aged 6–8 weeks and weighing 18–22 g, were provided by Jinan Pengyue Experimental Animal Breeding Co., Ltd.”

32 mice divided into four groups of 8 each; in vitro experiments used n=3 per group.

“Following a 1-week acclimatization period, the mice were randomly assigned to four groups (n = 8): Control, DSS, DSS + 5-ASA, and DSS + GHK-Cu.”

15 days for the in vivo experiment (12 days DSS exposure, 2 days recovery, euthanasia on day 15).

“In all groups aside from the Control, a 3% DSS solution was prepared using distilled water and administered as drinking water for 12 days, followed by a return to standard drinking water for the subsequent 2 days.”

GHK-Cu treatment alleviated DSS-induced colitis symptoms, including weight loss, disease activity index scores, and histopathological damage.

“GHK-Cu alleviated weight loss, improved the disease activity index (DAI), reduced colonic edema and shortening, attenuated inflammatory damage, increased goblet cell numbers, suppressed inflammatory cytokines such as TNF-α, IL-6, and IL-1β, and promoted mucosal repair.”

GHK-Cu upregulated SIRT1 expression and suppressed phosphorylated STAT3 (p-STAT3) in colon tissue and co-cultured cells.

“Results showed that GHK-Cu upregulated SIRT1 protein expression and suppressed the expression of phosphorylated p-STAT3 in colon tissue and MCECs of the co-culture model.”

Silencing STAT3 canceled the effect of GHK-Cu on promoting mucosal healing and tight junction protein expression.

“Our findings revealed that after transfection with STAT3-targeting siRNA (siSTAT3), the stimulant effect of GHK-Cu on the healing of MCECs and the effect on the protein expression of ZO-1 and Occludin is canceled.”