TITLE:
Protective Effects of Extracts, Isolated Compounds from Desmodium uncinatum and Semi-Synthetic Isovitexin Derivatives against Lipid Peroxidation of Hepatocyte’s Membranes
AUTHORS:
Borice T. Tsafack, Cyrille L. K. Bomgning, Jonas Kühlborn, Romuald T. Fouedjou, Beaudelaire K. Ponou, Remy B. Teponno, Agathe L. Fotio, Luciano Barboni, Till Opatz, Télesphore B. Nguelefack, Léon A. Tapondjou
KEYWORDS:
Desmodium uncinatum, Hepatoprotective Activity, Lipid Peroxidation, Hepatocyte Membranes, C-glycosylflavonoids
JOURNAL NAME:
Advances in Biological Chemistry,
Vol.8 No.6,
November
30,
2018
ABSTRACT: Lipid
peroxidation plays a pivotal role in the pathogenicity and maintenance of
hepatitis. Thus, substances protecting hepatocyte membranes from lipid
peroxidation are of great importance in the management of hepatotoxicity and
hepatitis. The present work deals with the in vitro hepatoprotective activity
of the methanol extract of Desmodium uncinatum, its sub-fractions, the major
isolated compounds and some of their semi-synthetic derivatives in order to
study structure activity relationships. Using hydrogen peroxide (H2O2)-induced
lipid peroxidation of hepatocyte membranes as a model, the
hepatoprotective-guided phytochemical survey of the methanol extract of aerial
parts of D. uncinatum was carried out by successive column chromatography. One
of the most active compounds (Isovitexin) was chemically transformed to yield
new semi-synthetic. The identification of isolated and semi-synthetic compounds
was performed using NMR techniques, mass spectrometry and by comparison of
their data with those reported in the literature. The n-butanol fraction was
the most effective (IC50: 22.9 μg/mL) compared to the crude methanol extract
(IC50: 43.6 μg/mL) and other fractions. The n-butanol sub-fractions FA
(containing non-phenolic compounds) and FB (mainly containing phenolic
compounds) exhibited respective IC50 of 14.36 and 128.2 μg/ml. Purification of
FA yielded 3-O-β-D-glucopyranosyl-β-sitosterol (1), 3-O-β-D-
2-acetyl-amino-2-deoxyglucopyranoxyloleanoic acid (2), (2S, 3S, 4R, 7R,
8Z)-1-O-β-D-glucopyranosyl-2-[(R)-2'-hydroxyarachidoylamino]-docosan-8-ene-3,4,7-triol (4), spiraeamide (5), mannitol (6), while FB afforded essentially three C-glycosylflavonoids namely isovitexin (7), vitexin (8) and vicenin-3 (9).
Chemical transformations (methylation, allylation and prenylation) of
isovitexin afforded five new semi-synthetic derivatives: 4',5,7-O-
trimethyli-sovitexin (10), 4'-O-allylisovitexin (11), 4',7-O-diallylisovitexin (12), 4'-O-prenylisovitexin (13) and 8-C-prenyl-4',7-O-diprenylisovitexin (14).
The screening of these derivatives revealed that allylation did not
significantly affect the hepatoprotective activity while methylation,
prenylation, number and position of sugar moieties on the A ring of flavonoids
significantly reduced it. Results demonstrated that the n-butanol fraction
obtained from the methanol extract of Desmdium uncinatum may possess
hepatoprotective activity due to its content in C-glycosylflavonoids and
cerebrosides. Hydroxyl groups in C-glycosylflavonoids are important for their
lipid peroxidation inhibitory activity.