인문학
사회과학
자연과학
공학
의약학
농수해양학
예술체육학
복합학
지원사업
학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
커뮤니티
연구자들이 자신의 연구와 전문성을 널리 알리고, 새로운 협력의 기회를 만들 수 있는 네트워킹 공간이에요.
초록·키워드
The development of natural peptides as direct Kelch-like ECH-associated protein 1 (Keap1)-nuclear factor erythroid2-related factor 2 (Nrf2) protein-protein interaction (PPI) inhibitors for antioxidant and anti-ferroptotic purposes has attracted increasing interest from chemists. <i>Radix Angelicae sinensis</i> (RAS) is a widely used traditional Chinese medicine with antioxidant capability. However, few studies have screened Keap1-Nrf2 PPI inhibitory RAS peptides (RASPs). This study optimized the extraction and hydrolysis protocols of RAS protein using response surface methodology coupled with Box-Behnken design. The molecular weight distribution of the prepared hydrolysates was analysed to obtain active fractions. Subsequently, ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry was employed to identify RASPs. Various <i>in vitro</i> and <i>in silico</i> assays were conducted to evaluate the antioxidant and anti-ferroptotic effects of RASPs. The results revealed that at least 50 RASPs could be obtained through the optimized protocols. RASPs containing active residues effectively scavenged 2,2-diphenyl-1-picrylhydrazyl radical and 2,2'-azinobis(3-ethylbenzothiazoline)-6-sulfonic acid radical cation. They also showed cytoprotective effect against erastin-induced ferroptosis in HT22 cells, which was characterized by the activation of Nrf2 and weakened under the incubation of an Nrf2 inhibitor. Moreover, RASPs could bind to Keap1 and then dissociate Nrf2 in molecular dynamics simulations. In conclusion, RASPs exhibit antioxidant activity through hydrogen atom transfer and electron transfer mechanisms. Importantly, they also inhibit ferroptosis by directly inhibiting Keap1-Nrf2 PPI.
인공지능 문자 인식 모델을 통해 추출된 텍스트로, 일부 오타나 오류가 포함될 수 있으나 지속적으로 개선 중입니다.
오류를 발견하셨다면 해당 부분을 드래그한 후 ' 를 통해 신고해주세요.
오류를 발견하셨다면 해당 부분을 드래그한 후 ' 를 통해 신고해주세요.