Anti-Lymphangiogenic Terpenoids from the Heartwood of Taiwan Juniper, Juniperus chinensis var. tsukusiensis
Journal
Plants (Basel, Switzerland)
Journal Volume
12
Journal Issue
22
Pages
Article number 3828
Date Issued
2023-11-11
Author(s)
Wu, Ho-Cheng
Shiu, Lung-Lin
Wang, Shih-Wei
Huang, Chia-Ying
Sung, Ping-Jyun
Kuo, Yueh-Hsiung
Abstract
To look in-depth into the phytochemical and pharmacological properties of Taiwan juniper, this study investigated the chemical profiles and anti-lymphangiogenic activity of Juniperus chinensis var. tsukusiensis. In this study, four new sesquiterpenes, 12-acetoxywiddrol (1), cedrol-13-al (2), α-corocalen-15-oic acid (3), 1,3,5-bisaoltrien-10-hydroperoxy-11-ol (4), one new diterpene, 1β,2β-epoxy-9α-hydroxy-8(14),11-totaradiene-3,13-dione (5), and thirty-three known terpenoids were successfully isolated from the heartwood of J. chinensis var. tsukusiensis. The structures of all isolates were determined through the analysis of physical data (including appearance, UV, IR, and optical rotation) and spectroscopic data (including 1D, 2D NMR, and HRESIMS). Thirty-four compounds were evaluated for their anti-lymphangiogenic effects in human lymphatic endothelial cells (LECs). Among them, totarolone (6) displayed the most potent anti-lymphangiogenic activity by suppressing cell growth (IC50 = 6 ± 1 µM) of LECs. Moreover, 3β-hydroxytotarol (7), 7-oxototarol (8), and 1-oxo-3β-hydroxytotarol (9) showed moderate growth-inhibitory effects on LECs with IC50 values of 29 ± 1, 28 ± 1, and 45 ± 2 µM, respectively. Totarolone (6) also induced a significant concentration-dependent inhibition of LEC tube formation (IC50 = 9.3 ± 2.5 µM) without cytotoxicity. The structure-activity relationship discussion of aromatic totarane-type diterpenes against lymphangiogenesis of LECs is also included in this study. Altogether, our findings unveiled the promising potential of J. chinensis var. tsukusiensis in developing therapeutics targeting tumor lymphangiogenesis.
Subjects
Juniperus chinensis var. tsukusiensis; Taiwan juniper; anti-lymphangiogenic activity; diterpenes; sesquiterpenes
Publisher
MDPI
Type
journal article