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New Cassane Diterpenoids from the Seed Kernels of Caesalpinia cucullata , Exhibit Anti‐inflammatory Effect in vitro by Inhibiting iNOS Enzymatic Activity
Author(s) -
Wang Miao,
Yang YiRen,
Yin Yan,
Song KaiRu,
Long LiPing,
Li XianZhe,
Zhou Bei,
Gao HuiYuan
Publication year - 2021
Publication title -
chinese journal of chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.28
H-Index - 41
eISSN - 1614-7065
pISSN - 1001-604X
DOI - 10.1002/cjoc.202000683
Subject(s) - chemistry , anti inflammatory , enzyme , caesalpinia , in vitro , inflammation , docking (animal) , nitric oxide synthase , stereochemistry , biochemistry , traditional medicine , pharmacology , biology , immunology , medicine , nursing
Main observation and conclusion Inflammation is a complex biological response to stimulation. Natural cassane diterpenoids from Caesalpinia genus exhibit significant anti‐inflammation activity. Eight new cassane diterpenoids (1—8) along with seven known ones (9—15) were obtained from the seed kernels of Caesalpinia cucullata Roxb. This is the first report on chemical investigation of the seed kernels of C. cucullata , and the cassane diterpenes were found in this plant for the first time. Their structures were elucidated based on the extensive spectroscopic analyses, and the absolute configurations were identified by ECD calculation and X‐ray crystallography. All compounds were evaluated for their anti‐inflammation activity by inhibiting NO production in LPS‐induced RAW 264.7 cells. Compounds 1—2 and 9—11 exhibited effective inhibitory activity with inhibition rate more than 50%. The iNOS enzyme activity and molecular docking experiments were performed to explore the preliminary mechanism. Eventually, a potential anti‐inflammatory mechanism revealed that the bioactive cassane inhibited overproduction of NO by targeting key residues in the iNOS active cavity to reduce iNOS enzymatic activation.