2. Academic Validation
  3. Anti-inflammatory bicyclic polyprenylated acylphloroglucinols with diverse architectures including an unprecedented 6/6/6 tricyclic core from Garcinia yunnanensis

Anti-inflammatory bicyclic polyprenylated acylphloroglucinols with diverse architectures including an unprecedented 6/6/6 tricyclic core from Garcinia yunnanensis

  • Bioorg Chem. 2024 Dec:153:107864. doi: 10.1016/j.bioorg.2024.107864.
Xin-Yue Hu 1,  Hui-Juan Luo 2,  Xin Wei 3,  Yu-Zhuo Wang 2,  Yan-Song Ye 4,  Shi-Jie Wan 5,  Dan Zheng 5,  Yu Zhou 1,  Hong-Xi Xu 6,  Xing-Ren Li 7,  Li-Gen Lin 8,  Gang Xu 9
Affiliations

Affiliations

  • 1 Key Laboratory of Phytochemistry and Natural Medicines, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, Yunnan, China; University of Chinese Academy of Sciences, Beijing 100049, China.
  • 2 State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China.
  • 3 School of Pharmacy, Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China.
  • 4 Key Laboratory of Phytochemistry and Natural Medicines, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, Yunnan, China.
  • 5 School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
  • 6 School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. Electronic address: xuhongxi88@gmail.com.
  • 7 Key Laboratory of Phytochemistry and Natural Medicines, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, Yunnan, China. Electronic address: lixingren@mail.kib.ac.cn.
  • 8 State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China. Electronic address: ligenl@um.edu.mo.
  • 9 Key Laboratory of Phytochemistry and Natural Medicines, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, Yunnan, China. Electronic address: xugang008@mail.kib.ac.cn.
PMID: 39383808 DOI: 10.1016/j.bioorg.2024.107864
Abstract

Garciyunnanol A (1), an unprecedented 1,2-seco-bicyclic polyprenylated acylphloroglucinol (BPAP) possessing a unique 6/6/6 tricyclic core, was characterized from Garcinia yunnanensis together with 16 BPAPs, including eight new compounds (garciyunnanols B-I, 2-9). Biogenetically, the bicyclo[3.3.1]nonane-2,4,9-trione moiety of 12 reconstructed the bicyclic δ-lactone core of 2 through Norrish type Ⅰ cleavage and cyclization, followed by a cyclization of two side chains to form an intriguing 6/6/6 tricyclic core of 1. Their structures were elucidated through analysis of spectroscopic data, calculation and comparison of ECD spectra. Bioactivity evaluation manifested that compounds 1, 2, 5, 6 and 14 demonstrated superior inhibition of NO production compared to the positive control dexamethasone. Notably, compound 5 exhibited a dose-dependent inhibitory effect on NO production, with an IC50 value of 0.25 ± 0.87 µM. Furthermore, experiments involving ELISA, Western blotting, and immunofluorescence staining revealed that 5 effectively reduced the secretion of interleukin-1β in LPS plus nigericin-stimulated THP-1 macrophages by inhibiting the activation of the NLRP3 inflammasome.

Keywords

1L-1β; Anti-inflammatory activity; BPAP; Garcinia yunnanensis; NLRP3.

Figures
Products