N-Acetyldopamine dimers from Oxya chinensis sinuosa attenuates lipopolysaccharides induced inflammation and inhibits cathepsin C activity

Computational and Structural Biotechnology Journal

Sun Chul Kang¹  Yun Suk Huh¹  MinKyun Na²  InWha Park²  Young-Kyu Han³  Tejinder Pal Khaket⁴  Vivek K. Bajpai⁵  Myunghee Kim⁵  Ashutosh Bahuguna⁶  Shruti Shukla⁷ 

[1] Corresponding authors.;College of Pharmacy, Chungnam National University, Daejeon 34134, Republic of Korea;Department of Biological Engineering, NanoBio High-Tech Materials Research Center, Inha University, Incheon 22212, Republic of Korea;Department of Biotechnology, Daegu University, Gyeongsan-si, Gyeongsangbuk-do 78453, Republic of Korea;Department of Energy and Materials Engineering, Dongguk University-Seoul, Seoul 04620, Republic of Korea;Department of Food Science and Technology, Yeungnam University, Gyeongsan-si, Gyeongsangbuk-do 38541, Republic of Korea;TERI–Deakin Nanobiotechnology Centre, The Energy and Resources Institute, Gwal Pahari, Gurugram, Haryana 122003, India;

关键词: Cathepsin C;    Essential dynamics;    Inflammation;    In silico;    NF-κB;    Oxya chinensis sinuosa;   

DOI  :  

来源: DOAJ

【 摘 要 】

Oxya chinensis sinuosa (rice field grasshopper) is an edible insect with numerous health beneficial properties, traditionally being used to treat many ailments in Korea and other countries. O. chinensis sinuosa has been used from centuries, however, a little is known about the chemical functionality of its bioactive compounds. Therefore, this study examined the anti-inflammatory and cathepsin C inhibitory activities of N-acetyldopamine dimer (2R, 3S)-2-(3′,4′-dihydroxyphenyl)-3-acetylamino-7-(N-acetyl-2″-aminoethyl)-1,4-benzodioxane (DAB1) isolated from O. chinensis sinuosa. Results showed that DAB1 reduced the expression of pro-inflammatory mediator (iNOS, COX-2) and cytokines (TNF-α, IL-1β, and IL-6), and curtailed the nuclear translocation of NF-κB by inhibiting the phosphorylation of IκBα in lipopolysaccharide stimulated macrophages. Additionally, DAB1 inhibited cathepsin C activity at the cellular level, supported by in vitro assay (Ki, 71.56 ± 10.21 µM and Kis, 133.55 ± 18.2 µM). Moreover, combinatorial molecular simulation and binding free energy analysis suggested a significant stability and binding affinity of cathepsin C-DAB1 complex via formation of hydrogen bond and hydrophobic interactions with the catalytic residues (Gln228, Thr379, Asn380, and Hie381). Also, essential dynamics analysis showed DAB1 induced non-functional motions in cathepsin C structure. Collectively, DAB1 was concluded as anti-inflammatory and cathepsin C inhibiting agent and could be used in the drug development against respective diseases.

【 授权许可】

Unknown