Study On Protective Effects Of Polysaccharide From Seeds Of Plantago Asiatica L.against Inflammation And Nonylphenol Exposure

Plantago asiatica L.is one of traditional medicinal and edible plants,which has a variety of biological activities,such as expectorant,antidiarrheal,diuresis,immunoregulation,antioxidant,hypoglycemia,hypolipidemic,and so on.In this study,the polysaccharide extracted from the seeds of Plantago asiatica L.,which were obtained from Ji'an,Jiangxi Province,was used to study its protective effects on liver inflammation,NP induced hepatotoxicity,nephrotoxicity,reproductive toxicity and intestinal barrier injury.Additionally,metabolomics was used to study its impact on characteristic metabolic markers of NP induced immune injury.The main research contents and conclusions are summarized as follows:1.Plantago asiatica L.crude polysaccharide(PLCP)protected liver injury induced by LPS in mice.Mice were pretreated orally with different dose of PLCP for 21 consecutive days.Then they were injected intraperitoneally with LPS and sacrificed 12 h later.Results showed that PLCP suppressed TNF-?,IL-6,IL-10,IL-2,and IL-1? overproduction in mice serum and liver.PLCP also enhanced GSH-Px and T-AOC activities in mice liver.In addition,PLCP inhibited NO,i NOS,and COX-2 expressions,and increased metallothionein production in mice liver.The results above indicated that PLCP may possess protective effects on inflammatory associated liver injury.2.PLCP had protective effects on hepatotoxicity induced by NP exposure in rats.SD rats were exposure orally to 50 mg/kg NP 1 h after different doses of PLCP intragastric administration consecutively for 45 days.The results showed that PLCP could decrease the relative weight of liver,increase the relative weight of thymus,improve the histomorphological injury of liver,and significantly decrease the expressions of ALT and AST in the serum.PLCP could also increase antioxidant enzyme activities in liver,reduce the expressions of MDA and i NOS,thus keep the balance between pro-oxidation and anti-oxidation.At the same time,PLCP inhibited the expressions of apoptosis-related proteins and m RNA in liver,inhibited mitochondrial-mediated apoptosis of hepatocytes,thereby protecting NP induced liver damage by regulating PI3K/Akt signaling pathway.In addition,it was also found via metabolomics analysis that 14 metabolites had significantly changed in liver after PLCP treatment,as well as the two metabolic pathways of Taurine and hypotaurine metabolism and Glutathione metabolism.The results above indicated that PLCP could alleviate hepatotoxicity caused by NP exposure.3.PLCP had a certain alleviating effect on renal injury caused by NP exposure in rat.The protective effect of PLCP on NP induced renal injury was studied.The results showed that PLCP could down-regulate the content of urea nitrogen in serum,increase the activities of renal CAT and GSH-Px enzymes,and reduce the espressions of MDA,LPO,i NOS and t NOS,thereby regulating the balance between ROS and antioxidant defense,and reducing the renal toxicity.The results indicated that PLCP had a certain protective effect on kidney injury caused by NP exposure.4.PLCP could alleviate reproductive system injury of rat caused by NP exposure.Male SD rats were exposure orally to 50 mg/kg NP 1 h after different doses of PLCP intragastric administration consecutively for 45 days.The results showed that NP induced significant decrease in relative weight of testes and epididymis,changed testicular histonorphology,and disrupted hormone secretions.Moreover,oxidative stress occurred after NP exposure by overproduction of MDA,LPO,i NOS,and low activities of SOD and CAT enzymes.Furthermore,the induction of apoptosis and disturbance of PI3K/Akt/m TOR pathway by NP were also proved.Interestingly,PLCP alleviated NP toxicity by improving antioxidant enzymes,recovering hormone secretions,inhibiting apoptosis and autophagy,which involves PI3K/Akt/m TOR pathway.The results above indicated that PLCP could alleviate reproductive system injury caused by NP exposure.5.Plantago asiatica L.polysaccharide(PLP)alleviated intestinal barrier damage caused by NP at the cellular level.Protective effect of PLP on NP induced intestinal barrier injury was explored in vitro by using Caco-2 cells and establishing Caco-2 cell monolayer model.The results showed that PLP pretreatment or co-cultured with NP significantly attenuated NP induced Caco-2 cytotoxicity,suppressed LDH release,restored the TEER value and paracellular permeability of Caco-2 monolayers,which were attributed to enhancing the tight junction protein expressions.In addition,PLP co-cultured with NP possessed better protective effects against NP induced cytotoxicity.This results indicated that PLP assuaged NP induced intestinal barrier injury by increasing tight junction in vitro.