Study on effects of Phyllanthusurinaria L extract Intervene Uric Acid in hyperuricemia mice

Objective:To investigate the effect ofPhyllanthusurinaria L extract on hyperuricemia mice.Methods:We were randomly divided into 6 groups by weight,control and model group,(15、30、45 mg/kg)ofPhyllanthusurinaria L extract group and allopurinol group.There were given oteracil potassium 300 mg/kg intragastrically to induce hyperuricemiamodel without control group,Phyllanthusurinaria L extract were given by intragastric administration,there were given saline solution instead as control and model group.Uric acid,blood urea ni-trogen and creatinine was detected in serum in n hyperuricemia mice for intragastric administration eight days.the contents and activity of xanthine oxidasein liver tissue were measured in hyperuricemia mice.The pathological changes of renal tissues were observed with HE staining in groups of mice.Western blot was surveied the expression of URAT1 protein in mice kidney tissues.Results:Groups ofPhyllanthusurinaria L extract could markedly reduce the uric acid,blood urea ni-trogen and creatinine level in serum on hyperuricemia mice,at the same time it reduce the contents and activity of liver in hyperuricemia mice,high dose group of Phyllanthusurinaria L extract did particularly well,close to allopurinol group,it could improve the pathologicalchanges in kidney tissueon hyperuricemia mice better than allopurinolgroup.the expressions of URAT1 protein of the model group was increased observbly than control group(P<0.05),but high dose group ofPhyllanthusurinaria L extract group wasdecreased more than model group,same level as control group(P<0.05).Conclusion:Phyllanthusurinaria L extractcould effectively were reduced the level of Uric acid in hyperuricemia mice,there were possibly reducing XOD activity,meanwhile,there were restrained the protein expression of URAT1 and decreased morphological changes in hyperuricemia mice.

Aryl hydrocarbon receptor signaling promotes ORMDL3- dependent generation of sphingosine-1-phosphate by inhibiting sphingosine-1-phosphate lyase

Aryl hydrocarbon receptor(AhR),a cellular chemical sensor,controls cellular homeostasis,and sphingosine-1-phosphate(S1P),a bioactive intermediate of sphingolipid metabolism,is believed to have a role in immunity and inflammation,but their potential crosstalk is currently unknown.We aimed to determine whether there is a functional linkage between AhR signaling and sphingolipid metabolism.We showed that AhR ligands,including an environmental polycyclic aromatic hydrocarbon(PAH),induced S1P generation,and inhibited S1P lyase(S1PL)activity in resting cells,antigen/IgE-activated mast cells,and mouse lungs exposed to the AhR ligand alone or in combination with antigen challenge.The reduction of S1PL activity was due to AhR-mediated oxidation of S1PL at residue 317,which was reversible by the addition of an antioxidant or in cells with knockdown of the ORMDL3 gene encoding an ER transmembrane protein,whereas C317A S1PL mutant-transfected cells were resistant to the AhR-mediated effect.Furthermore,analysis of AhR ligand-treated cells showed a time-dependent increase of the ORMDL3–S1PL complex,which was confirmed by FRET analysis.This change increased the S1P levels,which in turn,induced mast cell degranulation via S1PR2 signaling.In addition,elevated levels of plasma S1P were found in children with asthma compared to non-asthmatic subjects.These results suggest a new regulatory pathway whereby the AhR–ligand axis induces ORMDL3-dependent S1P generation by inhibiting S1PL,which may contribute to the expression of allergic diseases.