The clickable activity-based probe of anti-apoptotic calenduloside E

  • Pharm Biol. 2019 Dec;57(1):133-139. doi: 10.1080/13880209.2018.1557699.
Yu Tian  1  2  3  4  5 ,  Shan Wang  1  2  3  4  5 ,  Hai Shang  1  2  3  4  5 ,  Wen-Qian Wang  6 ,  Bao-Qi Wang  7 ,  Xi Zhang  7 ,  Xu-Dong Xu  1  2  3  4  5 ,  Gui-Bo Sun  1  2  3  4  5 ,  Xiao-Bo Sun  1  2  3  4  5
Affiliations
  • 1. a Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine , Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College , Beijing , China.
  • 2. b Key Laboratory of Bioactive Substances and Resources, Utilization of Chinese Herbal Medicine, Ministry of Education , Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College , Beijing , China.
  • 3. c Key Laboratory of Efficacy Evaluation of Chinese Medicine against Glycolipid Metabolic Disorders, State Administration of Traditional Chinese Medicine , Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College , Beijing , China.
  • 4. d Zhong guan cun Open Laboratory of the Research and Development of Natural Medicine and Health Products , Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College , Beijing , China.
  • 5. e Key Laboratory of new drug discovery based on Classic Chinese Academy of Medical Sciences.
  • 6. f Tianjin Institute of Pharmaceutical Research , Tianjin , China.
  • 7. g Center of Research and Development on Life Sciences and Environment Sciences, Harbin University of Commerce , Harbin , China.
PMID: 30843752 DOI: 10.1080/13880209.2018.1557699
Abstract

Context: Calenduloside E (CE), one of the primary natural products found in Aralia elata (Miq.) Seem. (Araliaceae), possesses prominent anti-apoptotic potential. A previous study found that one of the anti-apoptotic CE targets is heat shock protein 90 AB1 (Hsp90AB1) by probe CE-P, while the Other targets of CE still need to be identified with more efficient probes.

Objective: This study investigates CE analogue (CEA) as one clickable activity-based probe for use in exploring anti-apoptotic CE targets.

Materials and methods: Pretreatment of HUVECs with CEA (1.25 μM) for 8 hr, followed by ox-LDL stimulation for 24 h. Flow cytometry analysis and JC-1 staining assays were performed The kinetic constant measurements were tested by the Biacore T200, CM5 Sensor Chip which was activated by using sulpho-NHS/EDC. Ligands were dissolved and injected with a concentration of 12.5, 6.25, 3.125, 1.56, 0.78 and 0 μM.

Results: CEA was confirmed to possess an anti-apoptotic effect. The probable targets of CE/CEA were calculated, and as one of the higher scores proteins (Fit values: 0.88/0.86), HSP90 properly got our attention. Molecular modelling study showed that both CE and CEA could bind to HSP90 with the similar interaction, and the docking scores (S value) were -7.61 and -7.33. SPR assay provided more evidence to prove that CEA can interact with HSP90 with the KD value 11.7 µM.

Discussion and conclusions: Our results suggest that clickable probe CEA could alleviate ox-LDL induced Apoptosis by a similar mechanism of anti-apoptotic CE, and afforded the possibility of identifying additional anti-apoptotic targets of CE.

Keywords
CE analogue; Hsp90; SPR; molecular modelling; natural products.
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