Abstract:
ETHNOPHARMACOLOGICAL RELEVANCE:We recently reported that ethanol extract of Myrianthus arboreus P. Beauv. root bark demonstrated antidiabetic activity by modulating hepatocyte glucose homeostasis. This activity was associated significantly to the ethyl acetate (EAc) fraction. The current study sought to identify the active compounds responsible of the antidiabetic effect of M. arboreus in the EAc fraction using bioassay-directed sub-fractionation. MATERIALS AND METHODS:EAc fraction was sub-fractionated using Flash chromatography. Preparative HPLC was used to isolate the pure compounds. The structures of the isolated compounds were confirmed by analysis of NMR spectroscopic and mass spectrometric data. Hepatic (H4IIE, HepG2) cells were treated with maximum non-toxic concentrations of ethanol extract, its EAc fraction and isolated compounds thereof. Glucose-6-phosphatase (G6Pase) activity was measured using the glucose oxidase method. To measure glycogen synthase (GS) activity, radioactive assays were used. Phosphorylation of AMP-activated protein kinase (AMPK) and Glycogen Synthase Kinase-3 (GSK-3) were probed by Western blot. RESULTS:Six sub-fractions were obtained, and the antidiabetic activity was found in two sub-fractions (SFE1 and SFE2). For the first time, two known C-glycosylflavone regio-isomers, isoorientin (1) and orientin (2) were detected and isolated from M. arboreus plant, especially from SFE2 as well as protocatechuic acid, 3,4-dihydroxybenzaldehyde (4), and chlorogenic acid isolated from SFE1. The compounds 1, 2, 4 were determined to decrease the activity of G6Pase by increasing AMPK phosphorylation and to stimulate GS through GSK-3 phosphorylation. Isoorientin which is one of the main compounds of EAc fraction, expressed the strongest effect in all bioassays, similar to that of the EAc fraction. A significant and linear correlation was found between the phosphorylation of AMPK and the activity of G6Pase modulated by all samples (R2 = 0.54; p < 0.05). Similar to G6Pase assay, a correlation was determined between the capacity of M. arboreus extracts/fractions/compounds to stimulate GS activity and to phosphorylate GSK-3 (R2 = 0.57, p < 0.01). CONCLUSION:Results demonstrate that 1, 2, 4 are responsible, at least in part, for the antidiabetic activity of M. arboreus. These compounds can be used to ensure the quality and efficacy of M. arboreus antidiabetic preparations and standardize such preparations.
journal_name
J Ethnopharmacoljournal_title
Journal of ethnopharmacologyauthors
Kasangana PB,Eid HM,Nachar A,Stevanovic T,Haddad PSdoi
10.1016/j.jep.2019.112167subject
Has Abstractpub_date
2019-12-05 00:00:00pages
112167eissn
0378-8741issn
1872-7573pii
S0378-8741(19)31763-5journal_volume
245pub_type
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journal_title:Journal of ethnopharmacology
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journal_title:Journal of ethnopharmacology
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journal_title:Journal of ethnopharmacology
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journal_title:Journal of ethnopharmacology
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journal_title:Journal of ethnopharmacology
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journal_title:Journal of ethnopharmacology
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journal_title:Journal of ethnopharmacology
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journal_title:Journal of ethnopharmacology
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journal_title:Journal of ethnopharmacology
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journal_title:Journal of ethnopharmacology
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journal_title:Journal of ethnopharmacology
pub_type: 杂志文章
doi:10.1016/j.jep.2007.05.021
更新日期:2007-08-15 00:00:00
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journal_title:Journal of ethnopharmacology
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journal_title:Journal of ethnopharmacology
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更新日期:2016-07-21 00:00:00
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journal_title:Journal of ethnopharmacology
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journal_title:Journal of ethnopharmacology
pub_type: 杂志文章
doi:10.1016/j.jep.2015.04.001
更新日期:2015-06-20 00:00:00
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journal_title:Journal of ethnopharmacology
pub_type: 杂志文章
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journal_title:Journal of ethnopharmacology
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journal_title:Journal of ethnopharmacology
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journal_title:Journal of ethnopharmacology
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journal_title:Journal of ethnopharmacology
pub_type: 杂志文章,评审
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journal_title:Journal of ethnopharmacology
pub_type: 杂志文章
doi:10.1016/j.jep.2004.01.013
更新日期:2004-04-01 00:00:00
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journal_title:Journal of ethnopharmacology
pub_type: 杂志文章
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更新日期:1984-06-01 00:00:00
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journal_title:Journal of ethnopharmacology
pub_type: 杂志文章
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更新日期:2011-10-11 00:00:00
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journal_title:Journal of ethnopharmacology
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journal_title:Journal of ethnopharmacology
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journal_title:Journal of ethnopharmacology
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journal_title:Journal of ethnopharmacology
pub_type: 杂志文章
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更新日期:2021-01-30 00:00:00
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journal_title:Journal of ethnopharmacology
pub_type: 杂志文章
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更新日期:2019-03-01 00:00:00
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pub_type: 杂志文章
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更新日期:2021-01-10 00:00:00