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

Abstract

Sj?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.