Experimental study of the effects of oleanolic acid-aspirin conjugates on bone formation

JI Luhong; ZHAO Tingbo

doi:10.3969/j.issn.1002-7386.2017.15.004

Abstract：Objective To investigate the effects of oleanolic acid-aspirin conjugateson in inhibiting serotonin biosynthesis and promoting bone formation.Methods The inhibitor rate and contents of oleanolic acid-aspirin conjugates on tryptophan hydroxylase 1 (TPH-1) in RBL-2H3 cells,which was the principal enzyme in biosynthesis of serotonin,were detected by HPLC and ELISA kit.The rat models with osteoporosis were established by ovariectomy (OVX).Then the rats were randomly divided into oleanolic acid-aspirin conjugates group, oleanolic acid+aspirin group, oleanolic acid group (OA group),aspirin group,blank control group (OVX group),sham operation group (sham group) and positive drug control group,with 5 rats in each group.After 35-day medication,the levels of serotonin in serum and small intestine were detected by HPLC method,and the osteoblasts activities of promoting osteoblasts proliferation of oleanolic acid-aspirin conjugates were evaluated by using MTT assay.Results As compared with that in OA group, aspirin group and OA+aspirin group, the inhibitory ability on serotonin in oleanolic acid-aspirin conjugates group was significantly increased (P<0.05),with a dose-dependent manner.As compared with that in positive drug control group (LP533401), the inhibitory ability on serotonin in oleanolic acid-aspirin conjugates group at the concentration of 5μmol/L and 10μmol/L was significantly increased (P<0.05).As compared with OA group, aspirin group,OA+aspirin group, and oleanolic acid-aspirin conjugates group had no obvious toxicity on RBL-2H3 cells (P>0.05).As compared with OVX group,the oleanolic acid-aspirin conjugates group at the concentration of 10μmol/L could obviously inhibit the TPH-1 protein production (P<0.05).As compared with those in sham operation group, the levels of serotonin in serum and small intestine in OVX group were significantly increased (P<0.05).As compared with OVX group, the oleanolic acid-aspirin conjugates group at concentration of 10μmol/L could obviously decrease the levels of serotonin in serum and small intestine of rats (P<0.05).Moreover,as compared with OVX group, the oleanolic acid-aspirin conjugates could significantly inhibit osteoblasts formation (P<0.05).Conclusion The research results provide an new idea for development of anti-osteoporosis drugs like OA.