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postgraduate thesis: Protective effect of dendrobium officinale polysaccharides on experimental model of Sjögren's syndrome

TitleProtective effect of dendrobium officinale polysaccharides on experimental model of Sjögren's syndrome
Authors
Advisors
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.
DegreeDoctor of Philosophy
SubjectDendrobium - Therapeutic use.
Sjögren's syndrome.
Dept/ProgramChinese Medicine

 

DC FieldValueLanguage
dc.contributor.advisorZhang, Y-
dc.contributor.advisorZhang, Z-
dc.contributor.advisorSze, CW-
dc.contributor.authorLin, Xiang-
dc.contributor.author林响-
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.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-
dc.identifier.hkulb4786962-
dc.description.thesisnameDoctor of Philosophy-
dc.description.thesislevelDoctoral-
dc.description.thesisdisciplineChinese Medicine-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.5353/th_b4786962-
dc.date.hkucongregation2012-

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