Hexavalent chromium (K₂Cr₂O₇) induces liver damage in livestock, causing health and productivity losses. Prunella vulgaris polysaccharides (PVP) possess anti-inflammatory and antioxidant activities. This study applied network pharmacology, network toxicology, animal experiments and in-vitro assays to explore the protective effects of PVP on K₂Cr₂O₇-induced hepatotoxicity. Network toxicology and pharmacology identified TP53, HIF1A, MYC as potential targets and revealed a connection to oxidative stress and apoptosis pathways. In-vitro, PVP showed strong antioxidant activity. In K₂Cr₂O₇-challenged mice given PVP by gavage (75mg/kg, 32 days), body weight loss was rescued, liver fibrosis and serum ALT/AST were reduced (P<0.01), serum inflammation cytokines IL-6, TNF-α, IL-1β and IL-10 were balanced (P<0.05), oxidative stress enzymes T-AOC, GSH-Px and SOD were restored (P<0.05). 16S rRNA sequencing data suggested that PVP could alleviate intestinal flora disorders induced by K₂Cr₂O₇ and increased Lachnospiraceae_NK4A136_group levels. In AML-12 cells exposed to K₂Cr₂O₇ in-vitro, NQO1/HO-1/SOD2 levels were increased, MDA levels decreased, GSH concentrations elevated and ROS scavenged when PVP-containing serum was added to culture medium. Our findings reveal that PVP can protect mice from K₂Cr₂O₇-induced hepatotoxicity by inhibiting oxidative stress damage, blocking inflammatory responses and regulating the gut microbiota balance.

To Cite This Article: Li Y, Zhang X, Han Y, Ren H, Wang H, Fan B, Xie Y, Li X, Li M, Cheng S, Cao X, Pan Y, Zhou G and Sun J, 2026. Prunella vulgaris polysaccharides counteract chromium-induced liver injury via antioxidant and gut microbiota pathways. Pak Vet J, 2026, 46(10): 2552-2562. http://dx.doi.org/10.29261/pakvetj/2026.254