Anti-inflammatory Cassane-Type Diterpenoids from the Seed Kernels of Caesalpinia sinensis.
Miao WangSiyu YuShizhou QiBaohui ZhangKairu SongTing LiuHuiyuan GaoPublished in: Journal of natural products (2021)
Eighteen cassane diterpenoids, including five new lactam-type (4-8), 12 new lactone-type (1-3 and 9-17), and one known compound (18), were isolated from Caesalpinia sinensis. To our knowledge, this is the first study on the seed kernels of C. sinensis, and cassane derivatives were discovered in this plant for the first time. Their structures including absolute configurations were established by extensive spectroscopic methods complemented with single-crystal X-ray diffraction analyses and ECD calculations. Compounds 4-8 were identified as a group of rare cassane diterpenoids possessing a lactam D-ring instead of a typical lactone moiety. Biological evaluation revealed that compounds 4-6 exhibited effective inhibitory effects on NO production in the LPS-induced RAW 264.7 macrophages, with IC50 values in the range 8.2-11.2 μM. Compound 4 suppressed the excessive production of NO by down-regulating the expression of inducible nitric oxide synthase enzymes (iNOS) and reducing the enzymatic activity of iNOS. Moreover, the intermolecular interaction and binding mode between compound 4 and iNOS were elaborated by conducting a molecular docking study.
Keyphrases
- nitric oxide synthase
- molecular docking
- lps induced
- nitric oxide
- molecular dynamics simulations
- inflammatory response
- high resolution
- healthcare
- anti inflammatory
- computed tomography
- magnetic resonance
- magnetic resonance imaging
- binding protein
- mass spectrometry
- body mass index
- transcription factor
- crystal structure
- cell wall