Generic placeholder image

Current Bioactive Compounds


ISSN (Print): 1573-4072
ISSN (Online): 1875-6646

Research Article

β-Sitosterol Oxides From the Dried Stem of Salix gilgiana Inhibit the Proliferation of HL-60 Leukemic Cells

Author(s): Manami Oyama, Tetsuo Tokiwano, Hiromi Ota, Kouichi Mizuno, Keimei Oh, Satoru Kawaii and Yuko Yoshizawa*

Volume 16, Issue 3, 2020

Page: [329 - 334] Pages: 6

DOI: 10.2174/1573407214666181026110106

open access plus


Background: Salix gilgiana is a deciduous tree that grows in northern Japan, the Korean peninsula, eastern Russia along the Ussuri River, and northeast China. The stem of this tree is dried and consumed orally as a folk medicine. Our intensive screening of various plant materials found that the MeOH extract of its dried stem exhibited significant antiproliferative activity against HL-60 leukemic cells with an IC50 of 16 ppm. We systematically investigated the biologically active compounds of the MeOH extract of the dried stem of S. gilgiana.

Methods: The MeOH extract of S. gilgiana dried stem was fractionated by a repeated chromatography monitored by antiproliferative activity against HL-60 leukemic cells. Five active compounds were isolated and the structures were elucidated by MS, 1H- and 13C-NMR spectroscopy, and X-ray analysis.

Results: The active compounds were identified as 7-ketositosterol (I), 7β-hydroxysitosterol (II), 7α- hydroxysitosterol (III), (4-hydroxyphenyl)ethanol (IV), and (4-hydroxyphenyl)propan-1-ol (V). The strongest activity was found for 7α-hydroxysitosterol (III), with an IC50 of 8.4 µM. This is the first report of the isolation of these compounds from S. gilgiana.

Conclusion: Five compounds were isolated by a repeated chromatography under the guidance of antiproliferative bioassay using HL-60. The structures were identified as three β-sitosterol oxides and two phenolic compounds. Since Salix species, namely, willow trees, have beneficial characteristics including rapid growth, easy cloning, and resistance to high humidity and dryness, they may be utilized as a relatively inexpensive tool for the efficient production of useful bioactive materials.

Keywords: Salix gilgiana, HL-60, antiproliferative activity, 7-ketositosterol, salicin, bovine serum.

Graphical Abstract
Morita, N.; Shimizu, M.; Arisawa, M.; Kitanaka, S. Studies on medicinal resources. XXXV. The components of Salix plants (Salicaceae) in Japan. (2). The components of the leaves of Salix matsudana Koidz. f. tortuosa Rehd., and S. gilgiana Seemen (Article in Japanese, author’s translation). Yakugaku Zasshi, 1974, 94(7), 875-877.
[] [PMID: 4474400]
Oyama, M.; Tokiwano, T.; Kawaii, S.; Yoshida, Y.; Mizuno, K.; Oh, K.; Yoshizawa, Y. Protodioscin, isolated from the rhizome of Dioscorea tokoro collected in northern Japan is the major antiproliferative compound to HL-60 leukemic cells. Curr. Bioact. Compd., 2017, 13(2), 170-174.
[] [PMID: 28579930]
Jones, W.P.; Kinghorn, A.D. Biologically active natural products of the genus Callicarpa. Curr. Bioact. Compd., 2008, 4(1), 15-32.
[] [PMID: 19830264]
Jung, Y-J.; Park, J-H.; Shrestha, S.; Song, M-Y.; Cho, S.; Lee, C-H.; Han, D.; Baek, N-I. Phytosterols from the Rice (Oryza sativa) Bran. J. Appl. Biol. Chem., 2014, 57(2), 175-178.
Huh, G-W.; Park, J-H.; Shrestha, S.; Lee, Y-H.; Ahn, E-M.; Kang, H-C.; Baek, N-I. Sterols from Lindera glauca blume stem wood. J. Appl. Biol. Chem., 2011, 54(4), 309-312.
Zhang, X.; Geoffroy, P.; Miesch, M.; Julien-David, D.; Raul, F.; Aoudé-Werner, D.; Marchioni, E. Gram-scale chromatographic purification of β-sitosterol. Synthesis and characterization of β-sitosterol oxides. Steroids, 2005, 70(13), 886-895.
[] [PMID: 16038957]
Qi, W.Y.; Li, Y.; Hua, L.; Wang, K.; Gao, K. Cytotoxicity and structure activity relationships of phytosterol from Phyllanthus emblica. Fitoterapia, 2013, 84, 252-256.
[] [PMID: 23266735]
Koschutnig, K.; Heikkinen, S.; Kemmo, S.; Lampi, A.M.; Piironen, V.; Wagner, K.H. Cytotoxic and apoptotic effects of single and mixed oxides of beta-sitosterol on HepG2-cells. Toxicol. In Vitro, 2009, 23(5), 755-762.
[] [PMID: 19328846]
Gao, J.; Chen, S.; Zhang, L.; Cheng, B.; Xu, A.; Wu, L.; Zhang, X. Evaluation of cytotoxic and apoptotic effects of individual and mixed 7-ketophytosterol oxides on human intestinal carcinoma cells. J. Agric. Food Chem., 2015, 63(3), 1035-1041.
[] [PMID: 25542134]
Ramadan, M.F. Oxidation of β-sitosterol and campesterol in sunflower oil upon deep- and pan-frying of French fries. J. Food Sci. Technol., 2015, 52(10), 6301-6311.
[] [PMID: 26396375]
Lin, Y.; Knol, D.; Menéndez-Carreño, M.; Baris, R.; Janssen, H.G.; Trautwein, E.A. Oxidation of sitosterol and campesterol in foods upon cooking with liquid margarines without and with added plant sterol esters. Food Chem., 2018, 241, 387-396.
[] [PMID: 28958544]
Ishikawa, Y.; Sato, S.; Kurimoto, Y.; Yamada, H.; Hayakawa, A.; Hidaka, S. Preliminary study of phytoremediation and biomass production by Salix species on abandoned farmland polluted with heavy metals. Journal of Arid Land Studies, 2014, 23(4), 167-172.
Juga, A.; Makeschinb, F.; Rehfuessa, K.E.; Hofmann-Schiellea, C. Short-rotation plantations of balsam poplars, aspen and willows on former arable land in the Federal Republic of Germany. III. Soil ecological effects. For. Ecol. Manage., 1999, 121, 85-99.

© 2022 Bentham Science Publishers | Privacy Policy