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

Canjie Li,Xuefang Zhuo,Wenzhi Wang,Zhaochun Zhan,Zhongnan Wu,Yubo Zhang,Yaolan Li,Haipeng Zhang,Guocai Wang,Qing Tang,Xin Sun,Wenjing Yin

doi:10.3389/fchem.2021.733350

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.

Highlights

Considering the potential anti-inflammatory activity of clerodane diterpenoids (Zhang et al, 2019), we evaluated the inhibitory effects of diterpenoids 1–5 on inflammation by testing the secretion level of inflammatory cytokines IL-6 and TNF-α on LPS-stimulated RAW 264.7 cells
We evaluated anti-angiogenesis activities of compounds according to junction densities, vessel percentage areas, and average vessel lengths
48.27 ± 1.98, and 8.62 ± 2.89 μM, respectively. These results revealed that compounds 1–5 significantly inhibited the tube formation of human umbilical vein endothelial cell (HUVEC) and showed their anti-angiogenesis activities

Summary

INTRODUCTION

The genus Croton (Euphorbiaceae) is a rich source of diterpenoids with interesting structural diversity such as clerodane-type (Campos et al, 2010; Khanitha and Damrong, 2011; Sun et al, 2014), kauritan-type (Dao et al, 2011; Suwancharoen et al, 2012), heliurane-type (Martha et al, 2011; Huang et al, 2014a), phorbol ester-type (Zhang et al, 2013; Corlay et al, 2014), and trachylobane-type (Martinsen et al, 2010) These diterpenoids exhibited remarkable biological characteristics including anti-inflammatory (Wang et al, 2015), anti-tumor (Fernandes et al, 2013; Young et al, 2013; Maslovskaya et al, 2015), anti-viral (Nina et al, 2014), anti-bacterial (Liu et al, 2014), and anti-oxidation activities (Mariana et al, 2013), which make them valuable for phytochemical and pharmacological research studies. This article reported the isolation, structural elucidation, and evaluation of anti-inflammatory and antiangiogenic activities of the new compounds

RESULTS AND DISCUSSION

CONCLUSION

DATA AVAILABILITY STATEMENT