Background:The herbal medications are widely used in folk medicine for treatment of variable diseases and infection. Staphylococcus aureus (Sa) is a Gram-positive bacteria that cause severe organ affection, especially in the lung. Nigella sativa (NS) and gum arabic (GA) are probiotics with multi-beneficial effects for human health. Aims and Objectives: The current study was outlined to examine the protective effect of NS and GA against SA induced serum alterations and changes in cytokines and antioxidants expressions. Materials and Methods: A total of 42 male Wistar rats were allocated into six groups (6 each). Control group without any treatment; SA group in a dose of 2 × 10 9 colony forming units /mL per rat. Rats in 3-6 groups served as SA infected groups and received NS for Group 3 (150 mg/kg b.w. daily), GA plus SA for Group 4 (10% wt/vol. daily), and SA group received a mixture of NS plus GA for Group 5, and SA administered group received Lactobacillus for Group 6 as a positive control. NS and GA were administered 2 weeks before SA infection and continued for 1 week. Serum levels of cytokines and oxidative stress biomarkers were measured. Lung tissues were examined at molecular levels for mRNA expression of inflammatory cytokines and antioxidants. Results: SA induced a significant decrease in serum levels of interleukin -6 (IL-6), IL-2, and tumor necrosis factor -alpha. NS induced significant decrease on examined cytokines levels in SA (P < 0.05). GA did not induce any additive changes in cytokines. When both NA and GA were administered together, NS induced additive inhibitory effect. SA injection induced significant increase in serum levels of catalase and glutathione reductase. NS induced additive significant increase on antioxidant levels in SA injected. GA did not induce any additive increase for examined antioxidant levels. NS decreased total bacterial count increased in SA group more significantly than the effect induced by NS. Conclusion: NS has the potential to control the degree of inflammation at the protein and gene levels of examined cytokines (T-helper1/T-helper2) and antioxidants compared to the effect induced by GA.

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