Diterpenoids as potential anti-inflammatory agents from Ajuga pantantha

Wenpei Liu; Ziteng Song; Huimei Wang; Xueyuan Yang; Elizabeth Joubert; Jie Zhang; Shen Li; Muhetaer Tuerhong; Munira Abudukeremu; Jin Jin; Jing Xu; Dongho Lee; Yuanqiang Guo

doi:10.1016/j.bioorg.2020.103966

Diterpenoids as potential anti-inflammatory agents from Ajuga pantantha

Bioorg Chem. 2020 Aug:101:103966. doi: 10.1016/j.bioorg.2020.103966. Epub 2020 May 22.

Authors

Wenpei Liu¹, Ziteng Song², Huimei Wang¹, Xueyuan Yang¹, Elizabeth Joubert³, Jie Zhang⁴, Shen Li¹, Muhetaer Tuerhong⁵, Munira Abudukeremu⁵, Jin Jin¹, Jing Xu⁶, Dongho Lee⁷, Yuanqiang Guo⁸

Affiliations

¹ State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, Tianjin Key Laboratory of Molecular Drug Research, and Drug Discovery Center for Infectious Disease, Nankai University, Tianjin 300350, China.
² State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, Tianjin Key Laboratory of Molecular Drug Research, and Drug Discovery Center for Infectious Disease, Nankai University, Tianjin 300350, China; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
³ Plant Bioactives Group, Post-Harvest and Agro-Processing Technologies, Agricultural Research Council (ARC), Infruitec-Nietvoorbij, Private Bag X5026, Stellenbosch 7599, South Africa; Department of Food Science, Stellenbosch University, Private Bag X1, Matieland, Stellenbosch 7602, South Africa.
⁴ Key Laboratory for Green Processing of Chemical Engineering of Xinjiang Bingtuan, School of Chemistry and Chemical Engineering, Shihezi University, Shihezi 832003, China.
⁵ College of Chemistry and Environmental Sciences, Laboratory of Xinjiang Native Medicinal and Edible Plant Resources Chemistry, Kashgar University, Kashgar 844000, China.
⁶ State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, Tianjin Key Laboratory of Molecular Drug Research, and Drug Discovery Center for Infectious Disease, Nankai University, Tianjin 300350, China. Electronic address: xujing611@nankai.edu.cn.
⁷ Department of Biosystems and Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 136-713, Republic of Korea.
⁸ State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, Tianjin Key Laboratory of Molecular Drug Research, and Drug Discovery Center for Infectious Disease, Nankai University, Tianjin 300350, China; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China. Electronic address: victgyq@nankai.edu.cn.

PMID: 32506016
DOI: 10.1016/j.bioorg.2020.103966

Abstract

A phytochemical survey to obtain bioactive natural products from Ajuga pantantha afforded five new neo-clerodane diterpenoids (1-5). The structures were established by analysis of their NMR spectroscopic data, and electronic circular dichroism calculations were applied to define their absolute configurations. Compounds 2 and 5 were found to have the property of inhibiting NO production (IC₅₀ values < 40 μM). Molecular docking and Western blotting were used to study the mechanism of anti-inflammatory action. Furthermore, compound 5 with the highest activity was tested for its in vivo anti-inflammatory effects using a zebrafish model.

Keywords: Ajuga pantantha; Diterpenoids; Inflammation; Molecular docking; Nitric oxide inhibitory effects; Zebrafish model.

Publication types

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

MeSH terms

Ajuga / chemistry*
Animals
Anti-Inflammatory Agents / chemistry*
Disease Models, Animal
Diterpenes, Clerodane / pharmacology
Diterpenes, Clerodane / therapeutic use*
Molecular Docking Simulation / methods*
Molecular Structure
Phytochemicals
Zebrafish

Substances

Anti-Inflammatory Agents
Diterpenes, Clerodane
Phytochemicals