Prevention Effects Of Polysaccharides From Dendrobium Huoshanense On Carbon Tetrachloride-induced Acute Hepatotoxicity In Rats And Their Mechanisms Based On Intestinal Immunoregulating Activity

Dendrobium huoshanense, a rich source of active polysaccharides, is a famousChinese Traditional Medicine (TCM) and has been used in China for centires. Somestudies suggested that polysaccharides from Dendrobium huoshanense (DHP)possessed immunoregulation activity and prevention activity of liver injury andhepatic fibrosis. Moreover, their liver protection activities were correlated with theimmunoregulation activity. As far as our literature can be ascertained, the mechanismsof these activities of polysaccharides and their intrinsic connections betweenimmunoregulation and liver protection are not well known.As the development of immunology, researchers found that the gut-associatedlymphoreticular tissue (GALT) is the largest immune tissue in mammals whichcontain many immune tissues and immune cells. GALT can communicate with otherimmune tissues via lymph circulation and blood circulation. So we postulate that oraladministration of polysaccharides will firstly activate GALT, and then the activatedGALT will affect liver and spleen through lymph circulation and blood circulation tofulfill their immunoregulating activity and the liver protecting activity indirectly.Moreover, the immunoregulating activity of polysaccharides might be the basis of theliver protecting activity.After15-day oral administration of DHP, five mice were taken out from eachgroup to test the immunoregulating activity. Results showed that DHP stronglystimulated intestinal immune, hepatic immune and splenic immune in dose-dependedmanner. However, the immunoregulating activities were not observed in thehydrolyzates of DHP by trifluoroacetic acid (TFA), starch and dextran, whichindicated that the specific macromolecular structure was essential for DHP to performtheir immunoregulating activities. When the GALT was inhibited by20mgkg-1methotrexate, compared to normal group, production of bone marrowcell-proliferating cytokines of intestinal immune component cells were significantlyinhibited while the proliferating abilities of spleen cells and liver cells were normal inmodel group (MG) and low dose group of DHP (LDG,50mg kg-1day-1). In moderatedose group of DHP (MDG,100mg kg-1day-1), there are no notable differences in the proliferation of spleen cells and liver cells and the production of bone marrowcell-proliferating cytokines of intestinal immune component cells from those innormal group. As far as the high dose group of DHP (HDG,200mg kg-1day-1) wasconcerned, the proliferation of spleen cells and liver cells were enhanced as well asthe production of bone marrow cell-proliferating cytokines of intestinal immunecomponent cells. These results revealed that the hepatic and splenicimmunoregulating activity of DHP were dependent on their intestinalimmunoregulating activity. Linear regression analysis showed that the correlationcoefficient between intestinal immunostimulating activity and hepaticimmunostimulating activity or splenic immunostimulating activity of DHP wereR~2=0.9353and0.9463, respectively.The relationships of hepatic immunoregulating activity and liver protectingactivity of DHP were further investigated in this paper. Results indicated that DHPhave good potential for preventing carbon tetrachloride-induced acute hepatotoxicityin mice. There are no notable differences in serum aspartate aminotransferase (AST),serum alanine aminotransferase (ALT), hepatic malondialdehyde (MDA) and thehepatic total superoxide dismutase (T-SOD) activity in MG, LDG and MDG fromthose in solvent group (SG). In HDG, the activities of AST, ALT, MDA were muchlower than those in SG. With respect to T-SOD, the activity in mice of HDG wasmuch higher than those in SG. Linear regression analysis displayed that thecorrelation coefficient between liver protecting activity and hepatic immunoregulatingactivity of DHP was R~2=0.9359.Monosaccharide composition analysis showed that DHP was mainly composedof Xyl Glc Man and Gal with the raio of1.785:16.513:1:4.216, which was differentfrom the composition of other polysaccharides with intestinal immunostimulatingactivity.