|Title:||Neuroprotective effect by Z-ligustilide extracted from Radix Angelica sinensis for the treatment of cerebral ischemia|
|Subject:||Hong Kong Polytechnic University -- Dissertations|
Nervous system -- Diseases -- Chemotherapy
Cerebral ischemia -- Chemoprevention
|Department:||Department of Applied Biology and Chemical Technology|
|Pages:||338 leaves : ill. (some col.) ; 30 cm|
|Abstract:||Stroke resulting from cerebral ischemia is one of the leading causes of death and disability. To date, there is not yet any neuroprotective agent for the treatment of stroke. Involvement of oxidative stress in ischemic brain damage is established (Cassarino and Bennett, 1999; Simonian and Coyle, 1996). The overproduction of reactive oxygen species (ROS) such as superoxide anino, hydroxyl radical, and nitric oxide can directly react with and damage biomacromolecules by virtue of their reactivity that leads to neuronal cell death through necrosis, or, if in less intense cases, may mediate neuronal apoptosis through a cascade of biochemical process following cerebral ischemia (Li, et al., 1995; Ratan et al., 1994; Whittemore et al., 1995). Therefore, lipophilic antioxidants are of neuroprotective potential in the development of ischemic brain damage. Z-ligustilide (3-butylidene-4, 5-dihydro-phthalide, LIG) is a highly lipophilic compound extracted from Radix Angelica sinensis (Oliv.) Diels (Umbelliferae), known as Danggui in Chinese. Previous studies have shown that LIG has various bioactivities. Studies in this thesis evaluated, for the first time, the neuroprotective effect and the associated mechanisms of LIG in cerebral ischemia. In order to design the dosage regimen of LIG in vivo, its cellular permeability and transport pathways were first determined in Caco-2 monolayers. Our results show that oral application is the preferred route for the systemic administration of LIG. The free radical scavenging efficacy and the antioxidant activities of LIG were then evaluated in different in vitro ROS reactive systems, hydrogen peroxide-damaged C6 glioma cells and forebrain ischemic mice, respectively. We ascertain that LIG is a novel antioxidant and has significant protective effects against oxidative injury. The neuroprotective effects of LIG have been proven in transient forebrain ischemic mice and focal ischemic rats by measuring the histological, physiological, neurological or biochemical improvements after cerebral ischemia. The results suggest that postischemic treatment with LIG significantly ameliorates infarction volume by inhibiting both the apoptotic and necrotic cell death, and improving neurological deficits after transient cerebral ischemia. In addition, the multiple mechanisms, including the antioxidant, anti-apoptotic, and anti-inflammation properties, contribute to the neuroprotection of LIG. This thesis consists of 7 chapters, beginning with a general introduction, and then followed by the methodology section. There are then four chapters on results, and at the end, there is a general discussion.|
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