From by-product to biopeptide: Insight into the anti-inflammatory mechanism of peptides from rice dreg via peptidomics, multi-in silico, and in vitro approaches
Tingmin Qu, Ying Wu, Zhimin Zhang, Ziyi Chen, Hao Wu, Daichen Mu, Zhou Xu, Mao‐Long Chen, Yunhui Cheng, Wenzhi Tan, Yufei Xie, Qingming Huang, Hu Jian, Li Wen
Abstract
Rice dreg, an industrial waste abundant in high-quality proteins, has shown initial potential as a promising source of anti-inflammatory peptides. However, further investigation is essential to identify additional biopeptides and to fully clarify the underlying anti-inflammatory mechanisms. In this study, rice dreg hydrolysates with a degree of hydrolysis (DH) between 6% and 9% were evaluated and determined to exhibit optimal anti-inflammatory activity via peptidomics and multi- in silico . From the hydrolysates, 12 cytokine-inducing peptides were screened, including 5 significant peptides: IPLYQHIANLAGNK (PHP1), RGQLLIIPQHYAVVK (GAP1), INTYANFRDEVLPR (GEP1), GQLLIIPQHYAVVK (GAP2), and VSVVPSAAALVIK (OP1). All of these peptides were shown to effectively inhibit the release of pro-inflammatory cytokines in DC2.4 cells. Among them, PHP1 exhibited the most potent activity, not only inhibiting inflammation but also promoting the maturation of DC2.4 cells. Mechanistically, PHP1 modulated the mitogen-activated protein kinase (MAPK) signaling pathway by regulating the expression of key genes ( Igf1, Rasgrp2, Fgf20, Mapk4, Mapk10 , and Ptprr ) and the phosphorylation of p38 and c-Jun N-terminal kinase (JNK). Our findings suggest that PHP1 exerts its anti-inflammatory effects through suppression of the IL-17/MAPK signaling pathway and activation of the RAS-ERK signaling pathway. These findings offer a straightforward and effective method for the large-scale production of anti-inflammatory peptides. Additionally, the novel peptide PHP1, derived from rice dreg, holds significant promise for inclusion in nutritional therapies aimed at reducing inflammation.