Crassifolins Q−W: Clerodane Diterpenoids From Croton crassifolius With Anti-Inflammatory and Anti-Angiogenesis Activities

Abstract

Seven new clerodane diterpenoids, crassifolins Q−W (1–7), along with five known analogues (8–12), were isolated from the roots of Croton crassifolius. Their structures were identified by comprehensive spectroscopic analysis (UV, IR, NMR, and HR-ESI-MS), and their absolute configurations were determined by ECD spectra and X-ray crystallography. The activities of compounds 1–5 against inflammatory cytokines IL-6 and TNF-α levels on LPS-induced RAW 264.7 macrophages were assessed, and compound 5 showed the most significant activity with the secretion levels of IL-6 and TNF-α at 32.78 and 12.53%, respectively. Moreover, compounds 1–5 were screened for their anti-angiogenesis using a human umbilical vein endothelial cells in vitro mode; the results showed all of them exhibited obvious anti-angiogenesis activities, in particular, compound 5 showed the strongest anti-angiogenesis effect in the range of 6.25–50 μM.

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“… • Crocleropenes A and B ( 31 and 32 ) showed weak cytotoxicity against MCF7 cell lines (36 μM and 40 µM) ( Zou et al, 2020 ). • Crassifolins Q and R ( 33 and 34 ) were tested for anti-inflammatory and anti-angiogenesis activities showing moderate activities ( Li et al, 2021 ). • Mallotucin D 35 was isolated in 1981, along with mallotucin C, from Mallotus repandus ( Nakatsu et al, 1981 ).…”

“…• Crassifolins Q and R ( 33 and 34 ) were tested for anti-inflammatory and anti-angiogenesis activities showing moderate activities ( Li et al, 2021 ).…”

“…PLA 2 may be a target in cancer treatment because it is involved in pro-inflammatory and pro-tumoral pathways ( Peng et al, 2021 ; Vecchi et al, 2021 ). • Crassifolins S-U ( 50–52 ) were isolated from Croton crassifolius and tested for anti-inflammatory and anti-angiogenesis activities ( Li et al, 2021 ). All of them were active, and crassifolin U 52 was the most active for both bioactivities.…”

“…• Crassifolins S-U ( 50–52 ) were isolated from Croton crassifolius and tested for anti-inflammatory and anti-angiogenesis activities ( Li et al, 2021 ). All of them were active, and crassifolin U 52 was the most active for both bioactivities.…”

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“…After 12 h, the levels of IL-6 and tumour necrosis factor α (TNF-α) were evaluated with enzyme-linked immunoassay (ELISA) kits and crassifolin U ( 44 ) was able to decrease the levels of these pro-inflammatory cytokines, respectively, to 32.78% (IL-6) and 12.53% of those cells treated only with LPS. The anti-angiogenesis activity was assessed using tube formation assay in human umbilical vein endothelial cells (HUVECs) and crassifolin U ( 44 ) showed a strong anti-angiogenesis activity, reducing cavities formation, with IC 50 values of 7.20 μM (junction densities), 48.27 μM (vessel percentage areas), and 8.62 μM (average vessel lengths) [ 134 ].…”