Anti-lymphangiogenic diterpenes from the bark of Calocedrus macrolepis var. formosana

Tzong-Huei Lee ^a,1, Chin-Lin Hsieh ^b,c, Ho-Cheng Wu ^a, Shih-Wei Wang ^d,e,f,

Chen-Lin Yu ^d,e, George Hsiao ^g, Ming-Jen Cheng ^h, Wen-Tsong Hsieh ^i,1, Yueh-Hsiung Kuo ^j,k,l,*

a Institute of Fisheries Science, National Taiwan University, Taipei, 106, Taiwan

b Department of Chemistry, National Taiwan University, Taipei, 106, Taiwan

c Department of Disaster Management, Taiwan Police College, Taipei, 116, Taiwan

d Institute of Biomedical Sciences, MacKay Medical College, New Taipei City, 252, Taiwan

e Department of Medicine, Mackay Medical College, New Taipei City, 252, Taiwan

f Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan

g Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan

h Bioresource Collection and Research Center (BCRC), Food Industry Research and Development Institute (FIRDI), Hsinchu, 300,

Taiwan

i Department of Pharmacology, China Medical University, Taichung, 404, Taiwan

j Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, Taichung, 404, Taiwan

k Chinese Medicine Research Center, China Medical University, Taichung, 404, Taiwan

l Department of Biotechnology, Asia University, Taichung, 413, Taiwan

Eight new diterpenes, 6α,7β-dihydroxyferruginol (1), 6α,7α-dihydroxyferruginol (2), 6α-hydroxyhinokiol (3), 4α-hydroxy-7-oxo-18-norabieta-8,11,13-trien-4α-ol (4a), 15,16-dehydrosugiol (5), 7-methoxy-6,7-secoabieta-8,11,13-triene-6,12-diol (6), 7α-acetoxyabieta-8,12-diene-11,14-dione (7), 7α-butyloxyethyloxyabieta-8,12-diene-11,14-dione (8), along with four known compounds, 6,7-dehydroferruginol (9), 12-hydroxy-6,7-secoabieta-8,11,13-triene-6,7-dial (10), 7α-11-dihydroxy-12-methoxy-8,11,13-abietatriene (11), and 11,14-dihydroxy-8,11,13-abietatrien-7-one (12) were successfully isolated from the bark of Calocedrus macrolepis var. formosana. The structures of all isolates were elucidated by physical data (appearance, UV, IR, optical rotation) and spectroscopic data (1D, 2D NMR, and HREIMS). Compounds 9, 10, 11, and 12 showed promising growth-inhibitory effect on human lymphatic endothelial cells (LECs). Among these compounds, compound 10 exerted the most potent anti-lymphangiogenesis property by suppressing cell growth and tube formation of LECs. In conclusion, the results revealed the anti-lymphangiogenic potentials of Formosan C. macrolepis var. formosana.

Keywords: Anti-lymphangiogenesis, Calocedrus macrolepis var.formosana, Diterpenes

https://doi.org/10.38212/2224-6614.3375