Abietane diterpenoids from Orthosiphon wulfenioides with NLRP3 inflammasome inhibitory activity

Wen-Chao Tu; Ying-Xin Zhao; Chang-Lin Yang; Xing-Jie Zhang; Xiao-Li Li; Kaunda-Joseph Sakah; Rui-Han Zhang; Wei-Lie Xiao; Mei-Feng Liu

doi:10.1016/j.bioorg.2023.106534

Abietane diterpenoids from Orthosiphon wulfenioides with NLRP3 inflammasome inhibitory activity

Bioorg Chem. 2023 Jul:136:106534. doi: 10.1016/j.bioorg.2023.106534. Epub 2023 Apr 11.

Authors

Wen-Chao Tu¹, Ying-Xin Zhao², Chang-Lin Yang³, Xing-Jie Zhang², Xiao-Li Li², Kaunda-Joseph Sakah², Rui-Han Zhang², Wei-Lie Xiao⁴, Mei-Feng Liu⁵

Affiliations

¹ Key Laboratory of Functional Molecular Engineering of Guangdong Province, School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou 510640, PR China; Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education, Yunnan Characteristic Plant Extraction Laboratory, Yunnan Provincial Center for Research & Development of Natural Products, State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, School of Pharmacy and School of Chemical Science and Technology, Yunnan University, Kunming 650091, PR China.
² Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education, Yunnan Characteristic Plant Extraction Laboratory, Yunnan Provincial Center for Research & Development of Natural Products, State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, School of Pharmacy and School of Chemical Science and Technology, Yunnan University, Kunming 650091, PR China.
³ Key Laboratory of Functional Molecular Engineering of Guangdong Province, School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou 510640, PR China.
⁴ Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education, Yunnan Characteristic Plant Extraction Laboratory, Yunnan Provincial Center for Research & Development of Natural Products, State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, School of Pharmacy and School of Chemical Science and Technology, Yunnan University, Kunming 650091, PR China. Electronic address: xiaoweilie@ynu.edu.cn.
⁵ Key Laboratory of Functional Molecular Engineering of Guangdong Province, School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou 510640, PR China. Electronic address: liumf@scut.edu.cn.

PMID: 37068364
DOI: 10.1016/j.bioorg.2023.106534

Abstract

Wulfenioidones A - K (1-11) were abietane diterpenoids with highly oxidized 6/6/6 aromatic tricyclic skeleton isolated from the whole plant of Orthosiphon wulfenioides, and their planar structures and absolute configurations were elucidated by spectroscopic data interpretation, electronic circular dichroism calculation as well as X-ray crystallography analysis. Bioactivity screening indicated that compounds 1-4, 6 and 8 exhibited lactate dehydrogenase (LDH) inhibition effect with IC₅₀ values ranging from 0.23 to 3.43 μM by preventing the mononuclear macrophage cell pyroptosis induced by double signal stimulation of LPS and nigericin. Western Blot analyses of Caspase-1 and IL-1β down-regulation exhibited that compound 1 could selectively inhibit NLRP3 inflammasome, and the cell morphological observation further supported that compound 1 prevented macrophage cell pyroptosis.

Keywords: Abietane diterpenoid; NLRP3 inflammasome; Orthosiphon wulfenioides; Wulfenioidone.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Abietanes / chemistry
Abietanes / pharmacology
Inflammasomes*
Macrophages
NLR Family, Pyrin Domain-Containing 3 Protein
Orthosiphon*

Substances

Inflammasomes
NLR Family, Pyrin Domain-Containing 3 Protein
Abietanes