Hepatoprotective Effect of Flavonoid Glycosides from Lespedeza cuneata against Oxidative Stress Induced by tert‐Butyl Hyperoxide

Abstract

The aerial parts of Lespedeza cuneata G. Don, perennial legume native to Eastern Asia, have been used therapeutically in traditional Asian medicine to protect the function of liver, kidneys and lungs. However, little is known about the pharmaceutical effect of extracts from this plant. In the present study, the aerial parts of L. cuneata were used to prepare an ethanol extract, which was then tested for hepatoprotective effects against injury by tert-butyl hyperoxide (t-BHP). At a dose of 20 μg/mL, the ethanol extract significantly protected HepG2 cells against the cytotoxicity of t-BHP. Further fractionation of the extract with ethyl acetate allowed the isolation of five flavonoid compounds that were structurally identified by ¹H and ¹³C NMR spectroscopy as isovitexin, hirsutrin, trifolin, avicularin and quercetin. Hirsutrin, avicularin and quercetin (10 μM) showed clear hepatoprotective activity against injury by t-BHP in HepG2 cells, whereas isovitexin and trifolin showed no protective effects. The observed hepatoprotective effect of the investigated compounds showed a high correlation with radical scavenging activity, which followed the structure-activity relationships of the flavonoid aglycones.

“Qualitative and Quantitative Analysis of Flavonoids”

“…In addition flavonoids are known to inhibit lipidperoxidation, platelet aggregation, capillary permeability and fragility, cyclo-oxygenase and lipoxygenase enzyme activities. They exert these effects as antioxidants, free radical scavengers, chelators of divalent cation [15,39,40]. These are also reported to inhibit variety of enzymes like hydrolases, hyalouronidase, alkaline phosphatise, arylsulphatase, cAMP phosphodiesterase, lipase, α-glucosidase, kinase [41].…”

“…Flavonoids prevent synthesis of PGs that suppress T-cells. [40,53] and also inhibit neutrophil degranulation [40]. The figure (X) represents the effect of flavonoids in the treatment of inflammation.…”

“…The main antiaggregatory effect is by the inhibition of thromboxane A2 formation. Flavonoids like quercetin, kaempferol and myricetin are known to possess antiaggregatory properties [40,43] XVII) have also been shown to inhibit CYP3A4, which is the most abundant P450 enzyme in the liver and beneficial in metabolizing a significant number of carcinogens and medications [16]. Quercetin is abundantly found in human diet and it gets extensively metabolized during absorption in the small intestine and in the liver, and thus exerts a dose-dependent inhibitory effect on cell proliferation [55].…”

“…Given that the selectivity of flavonoids for eukaryotic enzymes appears to vary from compound to compound, a study regarding assessment of its toxicity is required to be done on these phytochemicals on an individual basis [10]. Flavonoids are found to be toxic to cancer or immortalized cells but are less toxic to normal cells [40]. Due to the low solubility of flavonoid aglycones in water, to the short residence time of flavonoids in the intestine, and to the low coefficient of absorption, it is not possible for humans to suffer acute toxic effects from the consumption of flavonoids, with the exception of a rare occurrence of allergy.…”

Antioxidant and Cytoprotective Activities of Flavonoid Glycosides-rich Extract from the Leaves of <i>Zanthoxylum bungeanum</i>

“…Flavonoid glycosides, typical phenolic compounds, are widely distributed in plants and play a significant role in plant biochemistry and physiology [12]. Additionally, they have been recognized to possess many bioactivities such as antioxidant, antiallergic, and hepatoprotective activities, as well as to be potent radical scavengers mostly due to their special chemical structure such as the position of hydroxyl groups, their polarity and aglycone moieties [13,14].…”