Potential natural product 3,4-seco-schitriterpenoids from Kadsura japonica L. as anti-neuroinflammatory agents

Shu-Hsiang Liu; Hung-Tse Huang; I-Wen Lo; Yu-Chi Lin; Geng-You Liao; Chih-Hua Chao; Hui-Chi Huang; Fang-Rong Chang; Tsung-Lin Li; Yuh-Chiang Shen; Chia-Ching Liaw

doi:10.1016/j.bioorg.2023.106843

Potential natural product 3,4-seco-schitriterpenoids from Kadsura japonica L. as anti-neuroinflammatory agents

Bioorg Chem. 2023 Dec:141:106843. doi: 10.1016/j.bioorg.2023.106843. Epub 2023 Sep 6.

Authors

Shu-Hsiang Liu¹, Hung-Tse Huang², I-Wen Lo³, Yu-Chi Lin², Geng-You Liao⁴, Chih-Hua Chao⁵, Hui-Chi Huang⁶, Fang-Rong Chang⁷, Tsung-Lin Li⁸, Yuh-Chiang Shen⁹, Chia-Ching Liaw¹⁰

Affiliations

¹ School of Nursing, National Taipei University of Nursing and Health Sciences, Taipei 112303, Taiwan.
² National Research Institute of Chinese Medicine, MOWH, Taipei 112026, Taiwan.
³ National Research Institute of Chinese Medicine, MOWH, Taipei 112026, Taiwan; Genomics Research Center, Academia Sinica, Taipei 115201, Taiwan.
⁴ Institute of Physiology, School of Medicine, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan.
⁵ Chinese Medicine Research and Development Center, China Medical University Hospital, Taichung 404332, Taiwan; School of Pharmacy, China Medical University, Taichung 406040, Taiwan.
⁶ Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, 404333, Taiwan.
⁷ Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 807378, Taiwan.
⁸ Genomics Research Center, Academia Sinica, Taipei 115201, Taiwan.
⁹ School of Nursing, National Taipei University of Nursing and Health Sciences, Taipei 112303, Taiwan; National Research Institute of Chinese Medicine, MOWH, Taipei 112026, Taiwan. Electronic address: yuchs@nricm.edu.tw.
¹⁰ National Research Institute of Chinese Medicine, MOWH, Taipei 112026, Taiwan; Department of Biochemical Science and Technology, National Chiayi University, Chiayi 600355, Taiwan. Electronic address: liawcc@nricm.edu.tw.

PMID: 37696148
DOI: 10.1016/j.bioorg.2023.106843

Abstract

In the present study, the undescribed schitriterpenoids, kadsujanonols A-I (1-9), and eleven reported compounds (10-20) were isolated from K. japonica L. vines. Their structures of 3,4-seco-schitriterpenoids were elucidated mainly by spectroscopic analyses including ¹H-, ¹³C-, and 2D-NMR, IR, HRESIMS spectra. The spatial configurations were determined by the single-crystal X-ray diffraction analysis of kadsujapnonol A (1), 15, 17, and 18, CD data and computational analysis. Furthermore, all isolates were evaluated for the anti-neuroinflammatory activity on LPS-stimulated NO production in BV2 microglial cells and compounds 2, 4, 5, 7, 9, 11, 13-16, and 18 exposed better or comparable suppression abilities than PDTC. Among them, kadlongilactone B (14) showed the best significant inhibiting ability (IC₅₀ = 0.87 μg/mL) and the effect is through the attenuation of the inflammatory transcription factor p65NF-κB. Preliminary structure-activity relationship revealed that δ-lactone at the side chain and 7-member lactone at C-3/C-4, and 3,4:9,10 ring opening are important.

Keywords: Anti-neuroinflammatory activity; Kadsujapnonol; Kadsura japonica L.; Scitriterpenoids; iNOS; p65NF-κB.

Publication types

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

MeSH terms

Kadsura* / chemistry
Lactones
Lipopolysaccharides / pharmacology
Microglia
Molecular Structure
Structure-Activity Relationship

Substances

Lactones
Lipopolysaccharides