Anti-inflammatory Cassane-Type Diterpenoids from the Seed Kernels of Caesalpinia sinensis

Abstract

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.

Interconvertible Pyridone Alkaloids from the Marine-Derived Fungus Penicillium oxalicum QDU1

“…Compounds 1 – 14 were also evaluated for their inhibitory effects on NO production in LPS-induced RAW264.7 cells by the Griess method (Table ). Compound 5 exhibited a moderate inhibitory effect on NO production with an IC 50 value of 9.2 μM. Compounds 1 , 4 , 8 , 10 , 11 , and 14 displayed weak inhibitory effects on NO production with IC 50 values of 15, 17, 19, 18, 17, and 14 μM, respectively.…”

“…Anti-inflammatory activities of all compounds were tested by the Griess method as previously reported methods in the literature . Macrophages (RAW264.7 mouse monocyte macrophage leukemia cells) are central cells participating in the inflammatory response.…”

“…Anti-inflammatory activities of all compounds were tested by the Griess method as previously reported methods in the literature. 25 Macrophages (RAW264.7 mouse monocyte macrophage leukemia cells) are central cells participating in the inflammatory response. RAW264.7 cells were induced by LPS (lipopolysaccharide) to produce the inflammatory cytokine NO, and the changes of NO were quantitatively investigated through the action of compounds to further judge the anti-inflammatory effects.…”

Guided Isolation of New Cytotoxic Cassane Diterpenoids from Caesalpinia sappan

“…Previous investigations on chemical constituents of C. sappan have reported a large number of naturally occurring molecules including cassanes, [3–7] flavones, [8] coumarins [9] . Among of these components, cassanes, as the typical and effective substances, [7] have been proved to exert extensive biological activities in terms of anti‐inflammatory effects on colitis, [10] arthritis [11] and asthma, [12] inhibitory effects on cancer cell lines, [13] renal fibrosis, [14] bacterial and glioblastoma, [15] especially in antiproliferative and anti‐inflammatory [16–19] . In the course of our ongoing search for bioactive cassanes with unique structures and promising tumor cells proliferation inhibitors, a series of diterpenoids and alkaloids have obtained from our studies on six Caesalpinia plants of C. bonduc , [12] C. sappan , [13] C. mimosoides , [14] C. sinensis , [19] C. minax , [20] C. cucullata [21] .…”

3-Deoxysappanchalcone isolated from Caesalpinia sinensis shows anticancer effects on HeLa and PC3 cell lines: invasion, migration, cell cycle arrest, and signaling pathway

“…Previous studies showed that a diet rich in flavonoids will reduce the risk of colon, prostate, and breast cancers [ 10 ]. Caesalpinia sinensis contains flavonoids, terpenoids, alkaloids, and steroids with anti-inflammatory, antioxidant, antiviral, antibacterial, and neuroprotective activities [ 11 , 12 ]. 3-deoxysulforaphane (3-DSC) is the active ingredient in C. sinensis [ 13 ].…”