2. Academic Validation
  3. Highly oxygenated ent-abietane diterpenoid lactones from Euphorbia peplus and their anti-inflammatory activity

Highly oxygenated ent-abietane diterpenoid lactones from Euphorbia peplus and their anti-inflammatory activity

  • Bioorg Chem. 2024 Nov 22:154:107989. doi: 10.1016/j.bioorg.2024.107989.
Ying Yan 1,  Ming-You Peng 1,  Ying Yang 2,  Zhi-Bi Zhang 3,  Long-Long Zhang 3,  Lei Tang 1,  Xu-Jie Qin 4,  Yuan-Yuan Cheng 5,  Ying-Tong Di 6,  Xiao-Jiang Hao 7
Affiliations

Affiliations

  • 1 State Key Laboratory of Functions and Applications of Medicinal Plants & College of Pharmacy, Guizhou Provincial Engineering Technology Research Center for Chemical Drug R&D, Guizhou Medical University, Guiyang 550014, China.
  • 2 Joint Laboratory for Translational Cancer Research of Chinese Medicine of the Ministry of Education of the People's Republic of China, Guangdong Key Laboratory for Translational Cancer Research of Chinese Medicine, International Institute for Translational Chinese Medicine, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, China.
  • 3 Academy of Biomedical Engineering, Kunming Medical University, Kunming 650500, Yunnan, China.
  • 4 Key Laboratory of Phytochemistry and Natural Medicines, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, Yunnan, China. Electronic address: qinxujie@mail.kib.ac.cn.
  • 5 Joint Laboratory for Translational Cancer Research of Chinese Medicine of the Ministry of Education of the People's Republic of China, Guangdong Key Laboratory for Translational Cancer Research of Chinese Medicine, International Institute for Translational Chinese Medicine, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, China. Electronic address: chengyuanyuan@gzucm.edu.cn.
  • 6 Key Laboratory of Phytochemistry and Natural Medicines, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, Yunnan, China. Electronic address: diyt@mail.kib.ac.cn.
  • 7 Key Laboratory of Phytochemistry and Natural Medicines, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, Yunnan, China.
PMID: 39591686 DOI: 10.1016/j.bioorg.2024.107989
Abstract

Eleven new ent-abietane diterpenoid lactones, designated euphjatrophanes H-R (1-11), were isolated from the whole Plants of Euphorbia peplus, along with nine previously identified congeners (12-20). Their structures, including absolute configurations, were elucidated through a combination of NMR, HRESIMS, single-crystal X-ray diffraction, and calculations of ECD and DP4 + technologies. Notably, the absolute configurations of six compounds 1, 2, 4, 5, 6, and 7 were unambiguously determined by single-crystal X-ray diffraction analyses, conducted with Cu Kα radiation. The anti-inflammatory potential of all ent-abietane diterpenoid lactones was evaluated on macrophages. Compounds 6-9, 12-16 and 19 significantly suppressed nitric oxide production, while 10 μM of compounds 6, 9, 11 and 16 remarkably suppressed the mRNA expression of IL-6, IL-1β, and TNFα in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages. Notably, compound 6 demonstrated a dose-dependent inhibition of the levels of inflammatory mediators (IL-6, IL-1β, and TNFα). Furthermore, compound 6 effectively suppressed FOXO1 expression and reduced the phosphorylation level of NF-κB p65. These findings suggest that compound 6 might be a promising candidate for treating inflammation-related diseases.

Keywords

Anti-inflammatory activity; Diterpenoid lactones; Ent-abietane; Euphorbia peplus; FOXO1.

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