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A Comparative Study of the Stability, Transport, and Structure–Activity Relationship of Round Scad Derived Peptides with Antineuroinflammatory Ability
Journal of Agricultural and Food Chemistry ( IF 5.7 ) Pub Date : 2024-07-19 , DOI: 10.1021/acs.jafc.4c03029 Qi Zhang 1, 2, 3 , Yali Wang 1, 2 , Lili Zhao 1, 2 , Guowan Su 3 , Wenping Ding 1, 2 , Lin Zheng 3 , Mouming Zhao 3
Journal of Agricultural and Food Chemistry ( IF 5.7 ) Pub Date : 2024-07-19 , DOI: 10.1021/acs.jafc.4c03029 Qi Zhang 1, 2, 3 , Yali Wang 1, 2 , Lili Zhao 1, 2 , Guowan Su 3 , Wenping Ding 1, 2 , Lin Zheng 3 , Mouming Zhao 3
Affiliation
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Our previous study identified round scad neuroprotective peptides with different characteristics. However, the intrinsic relationship between their structure and bioactivity, as well as their bioavailability, remains unclear. The aim of this study is to elucidate the bioavailability of these peptides and their structure–activity relationship against neuroinflammation. Results showed that the SR and WCP peptides were resistant to gastrointestinal digestion. Additionally, peptides SR, WCP, and WCPF could transport Caco-2 monolayers as intact peptides. The permeability coefficients (Papp) of SR, WCP, and WCPF in Caco-2 monolayer were (1.53 ± 0.01) × 10–5, (2.12 ± 0.01) × 10–5, and (8.86 ± 0.03) × 10–7 cm/s, respectively. Peptides SR, WCP, and WCPF, as promising inhibitors of JAK2 and STAT3, could attenuate the levels of pro-inflammatory cytokines and regulate the NFκB and JAK2/STAT3 signaling pathway in LPS-treated BV-2 cells. WCPF exerted the highest anti-inflammatory activity. Moreover, bioinformatics, molecular docking, and quantum chemistry studies indicated that the bioactivity of SR was attributed to Arg, whereas those of WCP and WCPF were attributed to Trp. This study supports the application of round-scad peptides and deepens the understanding of the structure–activity relationship of neuroprotective peptides.
中文翻译：
具有抗神经炎症能力的圆鲫衍生肽的稳定性、转运和构效关系的比较研究
我们之前的研究鉴定了具有不同特征的圆形scad神经保护肽。然而，它们的结构和生物活性以及生物利用度之间的内在关系仍不清楚。本研究的目的是阐明这些肽的生物利用度及其抗神经炎症的结构-活性关系。结果表明，SR 和 WCP 肽能够抵抗胃肠道消化。此外，肽 SR、WCP 和 WCPF 可以将 Caco-2 单层作为完整肽转运。 Caco-2单层中SR、WCP和WCPF的渗透系数（ P app ）分别为（1.53±0.01）× 10–5 、（2.12±0.01）× 10–5和（8.86±0.03）× 10–7分别为厘米/秒。肽 SR、WCP 和 WCPF 作为 JAK2 和 STAT3 的有前景的抑制剂，可以减弱 LPS 处理的 BV-2 细胞中促炎细胞因子的水平并调节 NFκB 和 JAK2/STAT3 信号通路。 WCPF 发挥最高的抗炎活性。此外，生物信息学、分子对接和量子化学研究表明，SR的生物活性归因于Arg，而WCP和WCPF的生物活性归因于Trp。该研究支持了round-scad肽的应用，并加深了对神经保护肽构效关系的理解。
更新日期：2024-07-19
中文翻译：
具有抗神经炎症能力的圆鲫衍生肽的稳定性、转运和构效关系的比较研究
我们之前的研究鉴定了具有不同特征的圆形scad神经保护肽。然而，它们的结构和生物活性以及生物利用度之间的内在关系仍不清楚。本研究的目的是阐明这些肽的生物利用度及其抗神经炎症的结构-活性关系。结果表明，SR 和 WCP 肽能够抵抗胃肠道消化。此外，肽 SR、WCP 和 WCPF 可以将 Caco-2 单层作为完整肽转运。 Caco-2单层中SR、WCP和WCPF的渗透系数（ P app ）分别为（1.53±0.01）× 10–5 、（2.12±0.01）× 10–5和（8.86±0.03）× 10–7分别为厘米/秒。肽 SR、WCP 和 WCPF 作为 JAK2 和 STAT3 的有前景的抑制剂，可以减弱 LPS 处理的 BV-2 细胞中促炎细胞因子的水平并调节 NFκB 和 JAK2/STAT3 信号通路。 WCPF 发挥最高的抗炎活性。此外，生物信息学、分子对接和量子化学研究表明，SR的生物活性归因于Arg，而WCP和WCPF的生物活性归因于Trp。该研究支持了round-scad肽的应用，并加深了对神经保护肽构效关系的理解。
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