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postgraduate thesis: Development of therapeutic approach to Wilson's disease using liposome-encapsulated curcumin
Title | Development of therapeutic approach to Wilson's disease using liposome-encapsulated curcumin |
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Authors | |
Advisors | Advisor(s):Tse, HF |
Issue Date | 2021 |
Publisher | The University of Hong Kong (Pokfulam, Hong Kong) |
Citation | Ho, W. I. [何慧賢]. (2021). Development of therapeutic approach to Wilson's disease using liposome-encapsulated curcumin. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. |
Abstract | Wilson’s disease (WD) is a rare inherited genetic disorder caused by lost-offunction mutations in the ATP7B gene. ATP7B protein dysfunction causes failure of copper metabolism and consequent accumulation of cytotoxic copper in a variety of tissues especially the liver and brain. Curcumin is a natural polyphenolic compound extracted from Curcuma longa plants that has been studied extensively and proven to have anti-inflammatory, antioxidative and hepatoprotective activities.
This study evaluated the therapeutic efficacy of the liposome encapsulated form of curcumin in both a cell and animal model of WD. The results revealed that treatment with liposome-encapsulated curcumin inhibited cell death induced by
copper chloride (CuCl2) of hepatocyte-like cells differentiated from WD patientspecific induced pluripotent stem cells (iPSCs). Also, when administered to 8-week-old Atp7b-/- WD mice, hepatosplenomegaly improved significantly along
with reduced AST and ALT levels, improved serum lipid profiles, reduced inflammatory cytokines, attenuated liver inflammation and fibrosis due to inhibited excretion of HMGB-1 protein, one of the initiators of an inflammatory response. Hepatic copper and copper excreted in urine and feces were nonetheless not significantly changed.
These results indicated a therapeutic effect of liposome-encapsulated curcumin to ameliorate liver injury and improve liver function in WD via its anti-inflammatory and anti-fibrotic effects. This agent offers potential as a preventive therapy in patients with WD. |
Degree | Master of Philosophy |
Subject | Hepatolenticular degeneration - Treament Curcumin |
Dept/Program | Medicine |
Persistent Identifier | http://hdl.handle.net/10722/313700 |
DC Field | Value | Language |
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dc.contributor.advisor | Tse, HF | - |
dc.contributor.author | Ho, Wai In | - |
dc.contributor.author | 何慧賢 | - |
dc.date.accessioned | 2022-06-26T09:32:35Z | - |
dc.date.available | 2022-06-26T09:32:35Z | - |
dc.date.issued | 2021 | - |
dc.identifier.citation | Ho, W. I. [何慧賢]. (2021). Development of therapeutic approach to Wilson's disease using liposome-encapsulated curcumin. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. | - |
dc.identifier.uri | http://hdl.handle.net/10722/313700 | - |
dc.description.abstract | Wilson’s disease (WD) is a rare inherited genetic disorder caused by lost-offunction mutations in the ATP7B gene. ATP7B protein dysfunction causes failure of copper metabolism and consequent accumulation of cytotoxic copper in a variety of tissues especially the liver and brain. Curcumin is a natural polyphenolic compound extracted from Curcuma longa plants that has been studied extensively and proven to have anti-inflammatory, antioxidative and hepatoprotective activities. This study evaluated the therapeutic efficacy of the liposome encapsulated form of curcumin in both a cell and animal model of WD. The results revealed that treatment with liposome-encapsulated curcumin inhibited cell death induced by copper chloride (CuCl2) of hepatocyte-like cells differentiated from WD patientspecific induced pluripotent stem cells (iPSCs). Also, when administered to 8-week-old Atp7b-/- WD mice, hepatosplenomegaly improved significantly along with reduced AST and ALT levels, improved serum lipid profiles, reduced inflammatory cytokines, attenuated liver inflammation and fibrosis due to inhibited excretion of HMGB-1 protein, one of the initiators of an inflammatory response. Hepatic copper and copper excreted in urine and feces were nonetheless not significantly changed. These results indicated a therapeutic effect of liposome-encapsulated curcumin to ameliorate liver injury and improve liver function in WD via its anti-inflammatory and anti-fibrotic effects. This agent offers potential as a preventive therapy in patients with WD. | - |
dc.language | eng | - |
dc.publisher | The University of Hong Kong (Pokfulam, Hong Kong) | - |
dc.relation.ispartof | HKU Theses Online (HKUTO) | - |
dc.rights | The author retains all proprietary rights, (such as patent rights) and the right to use in future works. | - |
dc.rights | This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. | - |
dc.subject.lcsh | Hepatolenticular degeneration - Treament | - |
dc.subject.lcsh | Curcumin | - |
dc.title | Development of therapeutic approach to Wilson's disease using liposome-encapsulated curcumin | - |
dc.type | PG_Thesis | - |
dc.description.thesisname | Master of Philosophy | - |
dc.description.thesislevel | Master | - |
dc.description.thesisdiscipline | Medicine | - |
dc.description.nature | published_or_final_version | - |
dc.date.hkucongregation | 2022 | - |
dc.identifier.mmsid | 991044545291003414 | - |