Polyphenolic-enriched extract has antioxidant and anti-inflammatory properties and helps maintain immune system balance; therefore, the aim of the study was to investigate the effects of polyphenol content in pomegranate peel extract on the immune system. Pomegranate (Punica granatum) processing generates substantial peel waste, which is rich in bioactive ellagitannins and flavonoids. This study investigates the therapeutic potential of pomegranate peel extract (PPE) to enhance immunity and restore tissue histology in mice challenged with carbon tetrachloride (CCl₄). In-vivo experiment, five distinct groups of male Swiss albino mice were as follow; T1, control group, T2, challenged group receiving carbon tetrachloride (CCl₄ at 1mL/kg, i.p., twice a week), T3 and T4 experimental CCl₄-challenged groups and treated with a low dose (100 mg/kg) or high dose (300 mg/kg) of PPE, and T5, positive control group given CCl₄ plus silymarin (50 mg/kg) to evaluate their effects on the immune system. All treatments were administered orally for 28 days. Assessed parameters included oxidative stress markers [malondialdehyde (MDA), protein carbonyl (PC)], antioxidant enzyme activities [superoxide dismutase (SOD), catalase (CAT), peroxidase (GPx), glutathione reduced (GSH)], immunological markers (serum immunoglobulins, IL-6, TNF-α, splenocyte proliferation), and histopathology of liver and spleen. HPLC analysis showed that the main compounds in PPE were punicalagin A (32.1mg/g), punicalagin B (15.6mg/g), ellagic acid (11.3mg/g), gallic acid (8.7mg/g) and catechin (4.2mg/g). PPE (300ug/ml) scavenged 82 and 38% of DPPH and ABTS free radicals, respectively. In-vivo, the PPE significantly (P<0.05) reversed oxidative stress by improving the activities of hepatic SOD, CAT and GPx and levels of GSH and markedly decreased MDA and PC in comparison with CCl₄. Immunologically, the PPE increased serum IgG/IgM, decreased pro-inflammatory cytokines (IL-6, TNF-α) and enhanced splenocyte proliferation. Histologically, the PPE significantly (P<0.05) attenuated the CCl₄-induced hepatocellular necrosis, inflammatory infiltration and splenic lymphoid depletion in a dose-dependent manner, with the high dose restoring near-normal architecture like silymarin. The pomegranate peel exhibits potent antioxidant activity, which ameliorates the oxidative stress induced by CCl₄. It boosts immunity and restores active tissue histology.

Majrashi KA, 2026. Pomegranate peel extract with antioxidant activity enhances immunity, growth performance, oxidative stress and tissue histology in CCl₄-challenged mice. Pak Vet J, 46(8): 2032-2042. http://dx.doi.org/10.29261/pakvetj/2026.200