School of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250300, China.
School of Pharmacy, Binzhou Medical University, Yantai 264003, China.
Molecules. 2023 Oct 12;28(20):7049. doi: 10.3390/molecules28207049.
The active peptide (APE) of Walker, which is prepared by bioenzymatic digestion, has significant antihyperlipidemic effects in vivo, but its mechanism of action on hyperlipidemia is not clear. Recent studies on amino acid metabolism suggested a possible link between it and hyperlipidemia. In this study, we first characterized the composition of APE using various methods. Then, the therapeutic effects of APE on hyperlipidemic rats were evaluated, including lipid levels, the inflammatory response, and oxidative stress. Finally, the metabolism-regulating mechanisms of APE on hyperlipidemic rats were analyzed using untargeted and targeted metabolomic approaches. The results showed that APE significantly reduced the accumulation of fat, oxidative stress levels, and serum pro-inflammatory cytokine levels. Untargeted metabolomic analysis showed that the mechanism of the hypolipidemic effect of APE was mainly related to tryptophan metabolism, phenylalanine metabolism, arginine biosynthesis, and purine metabolism. Amino-acid-targeted metabolomic analysis showed that significant differences in the levels of eight amino acids occurred after APE treatment. Among them, the expression of tryptophan, alanine, glutamate, threonine, valine, and phenylalanine was upregulated, and that of arginine and proline was downregulated in APE-treated rats. In addition, APE significantly downregulated the mRNA expression of SREBP-1, SREBP-2, and HMGCR. Taking these points together, we hypothesize that APE ameliorates hyperlipidemia by modulating amino acid metabolism in the metabolome of the serum and feces, mediating the SREBP/HMGCR signaling pathway, and reducing oxidative stress and inflammation levels.
沃克的活性肽（APE）是通过生物酶解制备的，在体内具有显著的降血脂作用，但作用机制尚不清楚。最近关于氨基酸代谢的研究表明，它与高血脂之间可能存在联系。在本研究中，我们首先使用各种方法对 APE 的组成进行了表征。然后，评估了 APE 对高脂血症大鼠的治疗效果，包括血脂水平、炎症反应和氧化应激。最后，使用非靶向和靶向代谢组学方法分析了 APE 对高脂血症大鼠的代谢调节机制。结果表明，APE 可显著减少脂肪堆积、氧化应激水平和血清促炎细胞因子水平。非靶向代谢组学分析表明，APE 降血脂作用的机制主要与色氨酸代谢、苯丙氨酸代谢、精氨酸生物合成和嘌呤代谢有关。氨基酸靶向代谢组学分析表明，APE 处理后 8 种氨基酸的水平存在显著差异。其中，色氨酸、丙氨酸、谷氨酸、苏氨酸、缬氨酸和苯丙氨酸的表达上调，精氨酸和脯氨酸的表达下调。此外，APE 还显著下调了 SREBP-1、SREBP-2 和 HMGCR 的 mRNA 表达。综上所述，我们假设 APE 通过调节血清和粪便代谢组中的氨基酸代谢，介导 SREBP/HMGCR 信号通路，降低氧化应激和炎症水平，改善高血脂。
