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Purpose <p>The present study demonstrates the combined effect of the probiotics as an adjunct and neurotensin (NTS) receptor 1 agonist PD149163 in modulating lipopolysaccharide (LPS) induced inflammation of the immune organs, specifically the spleen and thymus, in an endotoxemic mice model.</p> Methods <p>Mice (7–8&#xa0;weeks old) were divided into seven experimental groups (<i>n</i> = 6): Group I/control, while Groups II, III, IV, and VII were exposed to LPS (1&#xa0;mg/kg BW) intraperitoneally for five days. The NTS receptor 1/NTSR1 agonist PD149163 (50&#xa0;µg/kg BW) was administered to Groups III/V and VII for 28&#xa0;days. Multi-strain probiotics (0.6 gm/kg BW) were orally administered to LPS-exposed Groups IV/VII, and VI (the probiotics-only group) for 28&#xa0;days. The mice were anesthetized with pentobarbital (100&#xa0;mg/kg BW) and euthanized. Histopathological examination, ELISA of plasma NF-kβ, TNF-α, IL-6, IL-10, corticosterone (CORT) and NTS along with spectrophotometric detection of lipid peroxidation (LPx), superoxide dismutase (SOD) and catalase (CAT) were conducted on the immune organs, especially the spleen and thymus. Molecular docking studies were performed with the probiotic-derived bacteriocin, Plantaricin W and inflammation-associated proteins TNF-α and IL-6.</p> Results <p>The combination of probiotic supplementation and PD149163 reduced plasma levels of NF-kβ, TNF-a, IL-6, and CORT, while increasing IL-10 and NTS levels in LPS-treated mice. Additionally, this combination improved oxidative stress and histopathology in immune organs (spleen and thymus). Molecular docking studies suggested the potential of bacteriocin-producing probiotics as an adjunct intervention in reducing inflammation.</p> Conclusion <p>The combination of the probiotic and NTSR 1 agonist PD149163 might modulate inflammation of the spleen and thymus.</p> Graphical Abstract <p></p>

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Probiotic as an adjunct facilitates the anti-inflammatory efficacy of the neurotensin receptor 1 agonist PD149163: an in vivo and in silico study

  • 期刊论文

  • 发表日期：

    2025年9月15日

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  • Swarnima Mishra,
  • Banalata Mohanty

摘要

Purpose

The present study demonstrates the combined effect of the probiotics as an adjunct and neurotensin (NTS) receptor 1 agonist PD149163 in modulating lipopolysaccharide (LPS) induced inflammation of the immune organs, specifically the spleen and thymus, in an endotoxemic mice model.

Methods

Mice (7–8 weeks old) were divided into seven experimental groups (n = 6): Group I/control, while Groups II, III, IV, and VII were exposed to LPS (1 mg/kg BW) intraperitoneally for five days. The NTS receptor 1/NTSR1 agonist PD149163 (50 µg/kg BW) was administered to Groups III/V and VII for 28 days. Multi-strain probiotics (0.6 gm/kg BW) were orally administered to LPS-exposed Groups IV/VII, and VI (the probiotics-only group) for 28 days. The mice were anesthetized with pentobarbital (100 mg/kg BW) and euthanized. Histopathological examination, ELISA of plasma NF-kβ, TNF-α, IL-6, IL-10, corticosterone (CORT) and NTS along with spectrophotometric detection of lipid peroxidation (LPx), superoxide dismutase (SOD) and catalase (CAT) were conducted on the immune organs, especially the spleen and thymus. Molecular docking studies were performed with the probiotic-derived bacteriocin, Plantaricin W and inflammation-associated proteins TNF-α and IL-6.

Results

The combination of probiotic supplementation and PD149163 reduced plasma levels of NF-kβ, TNF-a, IL-6, and CORT, while increasing IL-10 and NTS levels in LPS-treated mice. Additionally, this combination improved oxidative stress and histopathology in immune organs (spleen and thymus). Molecular docking studies suggested the potential of bacteriocin-producing probiotics as an adjunct intervention in reducing inflammation.

Conclusion

The combination of the probiotic and NTSR 1 agonist PD149163 might modulate inflammation of the spleen and thymus.

Graphical Abstract