Techno-functional Starters Lab, National Collection of Dairy Cultures (NCDC), Dairy Microbiology Division, ICAR-National Dairy Research Institute, Karnal 132001, India.
Techno-functional Starters Lab, National Collection of Dairy Cultures (NCDC), Dairy Microbiology Division, ICAR-National Dairy Research Institute, Karnal 132001, India; Department of Nutrition and Integrative Physiology, Florida State University, Tallahassee, FL 32306, USA.
Peptides. 2022 Sep;155:170843. doi: 10.1016/j.peptides.2022.170843. Epub 2022 Jul 22.
Infections of microbial and non-microbial origins have been associated with significant immunological manifestations, thereby underscoring the need for a thorough understanding and investigation of novel immunomodulatory and antioxidant molecules that could prevent these incidences. To this end, we herein aim to identify fermented milk peptides with antioxidant and immunomodulatory properties that could be exploited for specific future applications. Our computational prediction models indicate that these peptides are non-toxic and possess considerable hydrophobicity (19.82-38.96 %) and functionality. Further analyses reveal that two of the four peptides, i.e., Pep 1 (AGWNIPM) and Pep 4 (YLGYLEQLLR), possess higher in-vitro antioxidant activity. The immunomodulatory potential of these two peptides (Pep 1 and Pep 4) is further demonstrated by using a combination of molecular simulation trajectory and ex-vivo approaches. Both peptides demonstrate ability to control the production of pro- inflammatory (TNF-α, IL-1, and IL-6) and anti-inflammatory (IL-10) cytokines as well as nitric oxide release in LPS-stimulated murine peritoneal macrophages. Similarly, peptide interferences also lead to significant (P < 0.05) improvement in macrophage phagocytic capacity. Taken together, these findings highlight the antioxidant and immunomodulatory properties of fermented milk peptides (Pep 1 and Pep 4) within the cellular environment and should facilitate prospective studies exploring such bioactive peptides and related functional molecules mediating the benefits of fermented milk products on human health.
微生物和非微生物来源的感染与显著的免疫表现有关，因此需要深入了解和研究新的免疫调节和抗氧化分子，以预防这些感染的发生。为此，我们旨在鉴定具有抗氧化和免疫调节特性的发酵乳肽，以便将来有针对性地应用。我们的计算预测模型表明，这些肽是非毒性的，具有相当大的疏水性（19.82-38.96%）和功能。进一步的分析表明，这四种肽中的两种，即肽 1（AGWNIPM）和肽 4（YLGYLEQLLR），具有更高的体外抗氧化活性。这两种肽（肽 1 和肽 4）的免疫调节潜力通过分子模拟轨迹和离体方法的组合进一步证明。这两种肽都能够控制促炎细胞因子（TNF-α、IL-1 和 IL-6）和抗炎细胞因子（IL-10）以及 LPS 刺激的小鼠腹腔巨噬细胞中一氧化氮的释放。同样，肽干扰也导致巨噬细胞吞噬能力显著提高（P < 0.05）。综上所述，这些发现强调了发酵乳肽（肽 1 和肽 4）在细胞环境中的抗氧化和免疫调节特性，并应促进探索此类生物活性肽和相关功能分子的前瞻性研究，这些分子介导发酵乳产品对人类健康的益处。
