Endometritis is a leading cause of reproductive failure in dairy cows, which is unfavorable for livestock production and the agricultural industry. Moreover, the widespread presence of antibiotic residues in milk after treatment raises serious public health concerns. The present study focuses on the protective interventions of Chebulagic Acid (CA) on lipopolysaccharide (LPS)-induced endometritis in dairy cow endometrium. The endometrial tissues were incubated with LPS and divided into the following five groups: control, LPS, LPS+CA, LPS+CA, and LPS+CA. The results showed in pathological histological changes and pro-inflammatory cytokines indicated the anti-inflammatory effect of CA on endometrial tissue. Through network pharmacology and molecular dockings, IL-1β, BCL2, TP53, TNF, and HIF-1A were identified as central therapeutic targets of CA. CA effectively downregulated the expression of HIF-1A and TP53. CA also suppressed the levels of COX-2, IL-1β, MMP-2, IL-6, iNOS, TNF-α, ALOX-15, and HMGB-1, thereby alleviating inflammation and safeguarding endometrial tissue in cases of endometritis. The results suggest that CA mitigates the synthesis of pro-inflammatory factors and protects the endometrium from inflammatory damage in dairy cows through the HIF-1α/p53 pathway.

To Cite This Article: Gao R, Bao F, Yang Y, Ren X, Zhao F, Althagafi H, Al-Shahari EA, Gong Z and Zhang Z, 2026. Chebulagic acid ameliorates LPS-induced endometritis by moderating hif-1ɑ/p53 signaling pathways in dairy cows. Pak Vet J, 46(3): 691-700. http://dx.doi.org/10.29261/pakvetj/2026.058