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Postgraduate Thesis: Protective effect of dendrobium officinale polysaccharides on experimental model of Sjögren's syndrome
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TitleProtective effect of dendrobium officinale polysaccharides on experimental model of Sjögren's syndrome
 
AuthorsLin, Xiang
林响
 
Issue Date2011
 
PublisherThe University of Hong Kong (Pokfulam, Hong Kong)
 
AbstractSj?gren’s syndrome (SS) is a chronic autoimmune disorder of the exocrine glands with clinical manifestation of dry eyes and dry mouth. The pathogenesis of SS is poorly understood, and efficient therapy is currently lacking. Therefore, an appropriate animal model recapitulating the key features of SS could be of profound value. Although several murine models have been established and evaluated, some of these models may develop other non-SS symptoms simultaneously. Herein, an autoimmunization-induced C57BL/6 female mouse model is evaluated. This mouse model exhibited less saliva secretion and swollen salivary gland with severe inflammation in the submandibular gland. Furthermore, apoptosis and pro-inflammatory cytokines were significantly increased and the expression of aquaporin 5, a water channel protein, was decreased and restricted to the basolateral membranes in acinar cells, indicating the weakening of water transport. Besides, autoantibodies such as Ro, La and other anti-nuclear autoantigens were found to be tremendously increased. The expression of M3 muscarinic receptor (M3R) increased in the acinar cells. This can be described as a compensatory expression due to the long term blockage from the autoantibodies which is similar in the SS patients. The characteristics of this model recapitulate the key features of human SS. Dendrobium officinale is an herbal medicine with yin-nourishing effect and clinically used in China as a health tonic to promote body fluid production. The polysaccharides extracted from Dendrobium officinale (DP) consisted of 6 monosaccharides: mannose, glucose, galactose, arabinose, xylose and glucuronic acid in the ratio of 10:0.25:1.2:4.7:1.3:1.4. DP was found to be protective on this experimental SS model. Specifically, administration of DP 20 mg/ml significantly prevented the chaos of immune responses and imbalance of pro-inflammatory cytokines. Our previous work also demonstrated that DP can promote saliva production in both SS patients and SS model. Therefore, we investigated the M3R activation induced by DP treatment. In contrast to the acute activation by acetylcholine, DP exerts slow, but long term activation on M3R. The botanical monosaccharides xylose and arabinose cannot be detected in the cell lysate, indicating that hydrolyzed DP did not permeate the cell membrane. Further investigations suggested that DP can inhibit the apoptosis induced by the addition of recombinant TNF-α on the human salivary gland epithelial cell line A-253. By investigating the potential mechanisms, we found that DP treatment can inhibit the apoptotic factors including the NF-κB activation, increased reactive oxygen species, decreased mitochondrial membrane potential and prolonged mitogen-activated protein kinase activation. The results suggested that DP may interfere with the TNF-α pathway and its receptor since DP did not permeate the cell membrane.
 
AdvisorsZhang, Y
Zhang, Z
Sze, CW
 
DegreeDoctor of Philosophy
 
SubjectDendrobium - Therapeutic use.
Sjögren's syndrome.
 
Dept/ProgramChinese Medicine
 
DC FieldValue
dc.contributor.advisorZhang, Y
 
dc.contributor.advisorZhang, Z
 
dc.contributor.advisorSze, CW
 
dc.contributor.authorLin, Xiang
 
dc.contributor.author林响
 
dc.date.hkucongregation2012
 
dc.date.issued2011
 
dc.description.abstractSj?gren’s syndrome (SS) is a chronic autoimmune disorder of the exocrine glands with clinical manifestation of dry eyes and dry mouth. The pathogenesis of SS is poorly understood, and efficient therapy is currently lacking. Therefore, an appropriate animal model recapitulating the key features of SS could be of profound value. Although several murine models have been established and evaluated, some of these models may develop other non-SS symptoms simultaneously. Herein, an autoimmunization-induced C57BL/6 female mouse model is evaluated. This mouse model exhibited less saliva secretion and swollen salivary gland with severe inflammation in the submandibular gland. Furthermore, apoptosis and pro-inflammatory cytokines were significantly increased and the expression of aquaporin 5, a water channel protein, was decreased and restricted to the basolateral membranes in acinar cells, indicating the weakening of water transport. Besides, autoantibodies such as Ro, La and other anti-nuclear autoantigens were found to be tremendously increased. The expression of M3 muscarinic receptor (M3R) increased in the acinar cells. This can be described as a compensatory expression due to the long term blockage from the autoantibodies which is similar in the SS patients. The characteristics of this model recapitulate the key features of human SS. Dendrobium officinale is an herbal medicine with yin-nourishing effect and clinically used in China as a health tonic to promote body fluid production. The polysaccharides extracted from Dendrobium officinale (DP) consisted of 6 monosaccharides: mannose, glucose, galactose, arabinose, xylose and glucuronic acid in the ratio of 10:0.25:1.2:4.7:1.3:1.4. DP was found to be protective on this experimental SS model. Specifically, administration of DP 20 mg/ml significantly prevented the chaos of immune responses and imbalance of pro-inflammatory cytokines. Our previous work also demonstrated that DP can promote saliva production in both SS patients and SS model. Therefore, we investigated the M3R activation induced by DP treatment. In contrast to the acute activation by acetylcholine, DP exerts slow, but long term activation on M3R. The botanical monosaccharides xylose and arabinose cannot be detected in the cell lysate, indicating that hydrolyzed DP did not permeate the cell membrane. Further investigations suggested that DP can inhibit the apoptosis induced by the addition of recombinant TNF-α on the human salivary gland epithelial cell line A-253. By investigating the potential mechanisms, we found that DP treatment can inhibit the apoptotic factors including the NF-κB activation, increased reactive oxygen species, decreased mitochondrial membrane potential and prolonged mitogen-activated protein kinase activation. The results suggested that DP may interfere with the TNF-α pathway and its receptor since DP did not permeate the cell membrane.
 
dc.description.naturepublished_or_final_version
 
dc.description.thesisdisciplineChinese Medicine
 
dc.description.thesisleveldoctoral
 
dc.description.thesisnameDoctor of Philosophy
 
dc.identifier.hkulb4786962
 
dc.languageeng
 
dc.publisherThe University of Hong Kong (Pokfulam, Hong Kong)
 
dc.relation.ispartofHKU Theses Online (HKUTO)
 
dc.rightsThe author retains all proprietary rights, (such as patent rights) and the right to use in future works.
 
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License
 
dc.source.urihttp://hub.hku.hk/bib/B47869628
 
dc.subject.lcshDendrobium - Therapeutic use.
 
dc.subject.lcshSjögren's syndrome.
 
dc.titleProtective effect of dendrobium officinale polysaccharides on experimental model of Sjögren's syndrome
 
dc.typePG_Thesis
 
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<item><contributor.advisor>Zhang, Y</contributor.advisor>
<contributor.advisor>Zhang, Z</contributor.advisor>
<contributor.advisor>Sze, CW</contributor.advisor>
<contributor.author>Lin, Xiang</contributor.author>
<contributor.author>&#26519;&#21709;</contributor.author>
<date.issued>2011</date.issued>
<description.abstract>&#65279;Sj?gren&#8217;s syndrome (SS) is a chronic autoimmune disorder of the exocrine

glands with clinical manifestation of dry eyes and dry mouth. The pathogenesis

of SS is poorly understood, and efficient therapy is currently lacking. Therefore,

an appropriate animal model recapitulating the key features of SS could be of

profound value. Although several murine models have been established and

evaluated, some of these models may develop other non-SS symptoms

simultaneously. Herein, an autoimmunization-induced C57BL/6 female mouse

model is evaluated. This mouse model exhibited less saliva secretion and

swollen salivary gland with severe inflammation in the submandibular gland.

Furthermore, apoptosis and pro-inflammatory cytokines were significantly

increased and the expression of aquaporin 5, a water channel protein, was

decreased and restricted to the basolateral membranes in acinar cells, indicating

the weakening of water transport. Besides, autoantibodies such as Ro, La and

other anti-nuclear autoantigens were found to be tremendously increased. The

expression of M3 muscarinic receptor (M3R) increased in the acinar cells. This

can be described as a compensatory expression due to the long term blockage

from the autoantibodies which is similar in the SS patients. The characteristics

of this model recapitulate the key features of human SS. Dendrobium officinale

is an herbal medicine with yin-nourishing effect and clinically used in China as

a health tonic to promote body fluid production. The polysaccharides extracted

from Dendrobium officinale (DP) consisted of 6 monosaccharides: mannose,

glucose, galactose, arabinose, xylose and glucuronic acid in the ratio of

10:0.25:1.2:4.7:1.3:1.4. DP was found to be protective on this experimental SS

model. Specifically, administration of DP 20 mg/ml significantly prevented the

chaos of immune responses and imbalance of pro-inflammatory cytokines. Our

previous work also demonstrated that DP can promote saliva production in both

SS patients and SS model. Therefore, we investigated the M3R activation

induced by DP treatment. In contrast to the acute activation by acetylcholine, DP

exerts slow, but long term activation on M3R. The botanical monosaccharides

xylose and arabinose cannot be detected in the cell lysate, indicating that

hydrolyzed DP did not permeate the cell membrane. Further investigations

suggested that DP can inhibit the apoptosis induced by the addition of

recombinant TNF-&#945; on the human salivary gland epithelial cell line A-253. By

investigating the potential mechanisms, we found that DP treatment can inhibit

the apoptotic factors including the NF-&#954;B activation, increased reactive oxygen

species, decreased mitochondrial membrane potential and prolonged

mitogen-activated protein kinase activation. The results suggested that DP may

interfere with the TNF-&#945; pathway and its receptor since DP did not permeate the

cell membrane.</description.abstract>
<language>eng</language>
<publisher>The University of Hong Kong (Pokfulam, Hong Kong)</publisher>
<relation.ispartof>HKU Theses Online (HKUTO)</relation.ispartof>
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<rights>Creative Commons: Attribution 3.0 Hong Kong License</rights>
<source.uri>http://hub.hku.hk/bib/B47869628</source.uri>
<subject.lcsh>Dendrobium - Therapeutic use.</subject.lcsh>
<subject.lcsh>Sj&#246;gren&apos;s syndrome.</subject.lcsh>
<title>Protective effect of dendrobium officinale polysaccharides on experimental model of Sj&#246;gren&apos;s syndrome</title>
<type>PG_Thesis</type>
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<description.thesisname>Doctor of Philosophy</description.thesisname>
<description.thesislevel>doctoral</description.thesislevel>
<description.thesisdiscipline>Chinese Medicine</description.thesisdiscipline>
<description.nature>published_or_final_version</description.nature>
<date.hkucongregation>2012</date.hkucongregation>
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