Bioactive peptides have been extensively applied for developing health-promoting foods. To improve the value of Laminaria japonica proteins (LJPs), anti-hypertensive peptides were prepared by using controlled enzymatic hydrolysis along with response surface methodology to improve their yields. Eight anti-hypertensive peptides with tyrosine (Tyr) at the C-terminal were determined through an efficient RP-HPLC method and molecular docking was performed to reveal the underlying mechanisms behind their effectiveness of anti-hypertension. According to the results, the strongest activity of hydrolysates was achieved under enzyme ratio (papain: alcalase: trypsin) 1:2:1, pH 8.0, temperature 60°C, substrate concentration 1.7%, enzyme addition 4.4%, and hydrolysis time 5.1 h. Furthermore, molecular docking results displayed that anti-hypertensive peptides could bind with ACE active sites through forming a stable composite structure, thus causing a significant reduction to activities. These results demonstrated the potential applications of LJPs as a source of anti-hypertensive peptides and provided a reference for the industrialized anti-hypertensive productions. Péptidos inhibidores de la ECA de Laminaria japonica y su potencial mecanismo antihipertensivo RESUMENLos péptidos bioactivos han sido aplicados ampliamente para preparar alimentos que promueven la salud. A fin de mejorar el valor de las proteínas de Laminaria japonica (LJP), en este estudio se prepararon péptidos antihipertensivos utilizando hidrólisis enzimática controlada junto con una metodología de superficie de respuesta destinada a mejorar su rendimiento. Mediante la aplicación de un método eficiente de RP-HPLC, estos procedimientos permitieron identificar ocho péptidos antihipertensivos con tirosina (Tyr) en el extremo C terminal, realizándose un acoplamiento molecular para revelar los mecanismos subyacentes a su eficacia antihipertensiva. De acuerdo con los resultados, la mayor actividad de los hidrolizados se alcanzó con una proporción de enzimas (papaína: alcalasa: tripsina) de 1:2:1, pH 8.0, temperatura de 60°C, concentración de sustrato del 1.7%, adición de enzimas de 4.4% y tiempo de hidrólisis de 5.1 horas. Por otra parte, los resultados de acoplamiento molecular mostraron que los péptidos antihipertensivos pueden unirse a los sitios activos de la ECA mediante la formación de una estructura compuesta estable, lo que provoca una reducción significativa de actividades. Estos resultados dan cuenta de las aplicaciones potenciales de los LJP como fuente de péptidos antihipertensivos y proporcionan una referencia para la producción de antihipertensivos industrializados.
No abstract
Ligusticum chuanxiong (LC) has been widely used for cardiovascular and cerebrovascular diseases. LC Hort extraction (LCE) can regulate high‐fat‐diet (HFD)‐induced lipid metabolic disorders (LMDs). However, the potential mechanism of LCE alleviates LMDs has not been entirely determined. This study aimed to investigate the potential effect of LCE in regulating LMDs and reveal its intervention mechanism. LCE was used as the alternative constituent to intervene in HFD‐induced LMDs. LCE antioxidant activity, toxicity, and the effects on serum lipid metabolism index were also determined. The potential intervention mechanism was investigated using the transcriptome analysis. Results confirmed that LCE administration remarkably decreased mice body weight, serum lipid indexes (total cholesterol [TC], triglyceride, low‐density lipoprotein cholesterol, nonesterified fatty acid, and total bile acid), and liver malondialdehyde levels. LCE intervention increased the serum high‐density lipoprotein cholesterol concentration and LPS enzyme activities, and LCE was nontoxic. The liver antioxidantive enzymes, such as catalase, superoxide dismutase, glutathione, lipoprotein lipase, and hepatic lipase, were enhanced. RNA‐seq Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis confirmed that LCE was mainly involved in the lipid metabolism–related signaling pathways, especially for cholesterol biogenesis and metabolic signaling pathways. Besides, genes, such as Cyp51, Msoml, Apof, Pmvk, Nsdh1, ApoA‐1, ApoC‐1, and Lcat, might have been upregulated, thus further inhibiting cholesterol synthesis. By upregulating genes related to the bile acid signaling pathway, such as CYP7A1, CYP27A1, and ABCG5/8, the conversion of TC into bile acid was accelerated, and cholesterol levels decreased. LCE could serve as an alternative Chinese medicine for alleviating HFD‐induced LMDs symptoms through multichannel interactions. This study provides a reference for exploring new functions of LC, especially for regulating LMDs.
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