Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/20428
Title: Isolation and identification of components from ixeris sonchifolia hance as potential anti-stroke agents
Authors: ZHANG YAOCHUN
Keywords: Ixeris sonchifolia Hance, stroke, flavonoids, antioxidant, anti-inflammatory, middle cerebral artery occlusion
Issue Date: 10-Aug-2010
Source: ZHANG YAOCHUN (2010-08-10). Isolation and identification of components from ixeris sonchifolia hance as potential anti-stroke agents. ScholarBank@NUS Repository.
Abstract: Ixeris sonchifolia Hance is a small and bitter perennial herb widely distributed in the northeastern part of China. Its raw extract had recently been developed into an injectable formulation showing considerable therapeutic efficacy in stroke management. But the biological targets and the underlying chemical components remained mostly unknown. Accordingly, (1) the effectiveness of the herbal preparation may suffer from batch-to-batch variations since it is difficult to ensure the presence of similar amounts of active ingredients, and (2) some of the components present in the herbal formation may pose certain side effects that potentially limit the therapeutic benefits. This thesis aimed to isolate and identify constituents from Ixeris sonchifolia Hance that display anti-stroke activities and to elucidate the possible mechanism(s) through which the identified compound(s) exerted the neuroprotective effects. To accomplish this objective, the aerial part of Ixeris sonchifolia Hance was extracted and the crude extract was partitioned into fractions. The fractions were then subjected to screening using both cell-based in vitro bioassays and biochemical reactions. The results had revealed that the ethyl acetate fraction, although failed to exhibit anticoagulant activities, dose-dependently protected cells from hydrogen peroxide-induced cytotoxicity, scavenged DPPH free radicals, induced ARE-dependent transcriptional activity and caused upregulation of Nrf2 protein levels. The follow-up isolation work focused on the ethyl acetate fraction revealed the presence of two classes of compounds: flavonoids and sesquiterpene lactones. In vitro bioassays conducted on the isolated flavonoids, which were identified to be Apigenin (1), Luteolin (2), Apigenin-7-O-?-glucopyranoside (3), Luteolin-7-O-?-glucopyranoside (4), Luteolin-7-O-?-glucruonopyranoside (5) and Luteolin-7-O-?-galacturonide (6) respectively, revealed that these compounds could protect cells from H2O2-induced cytotoxicity by scavenging free radical directly and inducing phase II enzymes, suggesting that the purified flavonoid compounds might exert neuroprotective effects during the early response, characterized by excitotoxic damage and oxidative stress, to stroke occurrence. Considering that the second wave of cell death after a stroke incident stems from the neuroinflammatory response, the anti-inflammatory effects of these isolated flavonoids on the LPS-stimulated cells were next determined. The results suggested that these flavonoid compounds might exert anti-inflammatory activities by regulating cytokine secretion, inhibiting Cox-2 expression, as well as reducing NO release and iNOS expression. As validation, the potential anti-stroke effects of Luteolin, a representative of these isolated flavonoid compounds, were investigated using rats suffering from cerebral ischemia induced by MCA occlusion. The results revealed that while treatment with Luteolin failed to neither reduce MCAO-induced mortality nor improve neurobehavioral recovery, it significantly reduced the infarct area, decreased the number of cells positively stained with anti-cleaved caspase-3 and anti-Cox-2 antibodies, suggesting that Luteolin might exert neuroprotective effects in an in vivo stroke model. In conclusion, extraction and isolation works focused on Ixeris sonchifolia Hance revealed the presence of two categories of compounds in the ethyl acetate fraction of its raw extract: flavonoids and sesquiterpene lactones. The isolated bioactive flavonoids were found to possess potential anti-stroke effects, which at least in part were attributed to their antioxidant and anti-inflammatory activities.
URI: http://scholarbank.nus.edu.sg/handle/10635/20428
Appears in Collections:Ph.D Theses (Open)

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