Marasinghe Chathuri Kaushalya, Jung Won-Kyo, Je Jae-Young
Department of Food and Life Science, Pukyong National University, Busan, Republic of Korea.
Major of Biomedical Engineering, Division of Smart Healthcare, Pukyong National University, Busan, Republic of Korea.
J Food Biochem. 2022 Dec;46(12):e14493. doi: 10.1111/jfbc.14493. Epub 2022 Oct 30.
Potential anti-inflammatory effects of ark shell (Scapharca subcrenata) protein hydrolysates were investigated. Ark shell protein hydrolysates were prepared using Alcalase® and pepsin and were designated ASAH and ASPH, respectively. The nitric oxide (NO) inhibitory activity of ASAH and ASPH was determined in lipopolysaccharides (LPS)-stimulated RAW264.7 murine macrophages, and the results showed that ASAH inhibited better NO inhibitory activity than ASPH. ASAH suppressed inflammatory mediator, a prostaglandin E2, secretion of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6), and production of reactive oxygen species (ROS) dose dependently. It inhibited the protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) and simulated heme oxygenase-1 (HO-1) protein expression. However, the pharmacological approach revealed that pretreatment with zinc protoporphyrin ІX (ZnPP), an inhibitor of HO-1, reversed the anti-inflammatory effect of ASAH. Moreover, ASAH upregulated phosphorylation of mitogen-activated protein kinases (MAPKs) including ERK1/2, JNK1/2, and p38 MAPK. To find out the role of MAPKs phosphorylation, MAPKs inhibitors were used, and the results showed that ASAH-mediated HO-1 protein expression and Nrf2 nuclear translocation were abolished. Taken all together, this study revealed that ASAH has a potential anti-inflammatory activity through regulation of the MAPK-dependent HO-1/Nrf2 pathway. PRACTICAL APPLICATIONS: Food-derived marine bioactive peptides, due to their pivotal role in biological activities, are gaining much attention recently. However, the anti-inflammatory activities of ark shell protein hydrolysates still remain to be investigated. This study investigated that ASAH shows potential anti-inflammatory activities through regulation of the MAPK-dependent HO-1/Nrf2 pathway in RAW264.7 murine macrophages. These findings indicated that ASAH may be used as a dietary supplement, functional food, and medicinal drug for the management of inflammation and inflammation-associated diseases.
研究了魁蚶（Scapharca subcrenata）蛋白水解物的潜在抗炎作用。使用碱性蛋白酶和胃蛋白酶制备魁蚶蛋白水解物，分别命名为ASAH和ASPH。在脂多糖（LPS）刺激的RAW264.7小鼠巨噬细胞中测定了ASAH和ASPH的一氧化氮（NO）抑制活性，结果表明ASAH的NO抑制活性优于ASPH。ASAH剂量依赖性地抑制炎症介质前列腺素E2、促炎细胞因子（TNF-α、IL-1β和IL-6）的分泌以及活性氧（ROS）的产生。它抑制诱导型一氧化氮合酶（iNOS）和环氧化酶-2（COX-2）的蛋白表达，并模拟血红素加氧酶-1（HO-1）蛋白表达。然而，药理学方法表明，用HO-1抑制剂原卟啉锌IX（ZnPP）预处理可逆转ASAH的抗炎作用。此外，ASAH上调了包括ERK1/2、JNK1/2和p38 MAPK在内的丝裂原活化蛋白激酶（MAPK）的磷酸化。为了探究MAPK磷酸化的作用，使用了MAPK抑制剂，结果表明ASAH介导的HO-1蛋白表达和Nrf2核转位被消除。综上所述，本研究表明ASAH通过调节MAPK依赖的HO-1/Nrf2途径具有潜在的抗炎活性。实际应用：食物来源的海洋生物活性肽由于其在生物活性中的关键作用，最近受到了广泛关注。然而，魁蚶蛋白水解物的抗炎活性仍有待研究。本研究调查了ASAH通过调节RAW264.7小鼠巨噬细胞中MAPK依赖的HO-1/Nrf2途径显示出潜在的抗炎活性。这些发现表明，ASAH可作为膳食补充剂、功能性食品和药物用于炎症及炎症相关疾病的管理。
