Effects of Heterocyclic Oleanolic Acid Derivatives-Aspirin Conjugates on Inhibition of Serotonin Biosynthesis and Increase of Bone Formation
10.3870/j.issn.1004-0781.2017.06.010
- VernacularTitle:杂环齐墩果酸衍生物-阿司匹林缀合物抑制血清素合成及促骨形成作用
- Author:
Luhong JI
;
Tingbo ZHAO
- Keywords:
Heterocyclic oleanolic acid-aspirin conjugates;
Oleanolic acid;
Aspirin;
Serotonin;
Osteoporosis
- From:
Herald of Medicine
2017;36(6):630-635
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the effects of the heterocyclic oleanolic acid derivatives-aspirin conjugates on inhibition of serotonin biosynthesis and increase of bone formation.Methods The inhibition rate,content and mRNA expression of heterocyclic oleanolic acid derivatives-aspirin conjugates on tryptophan hydroxylase 1 (TPH-1),which was the principal enzyme in the biosynthesis of serotonin,were tested by HPLC,ELISA kit and real-time PCR,respectively.Osteoporosis model was established by ovariectomy (OVX).The rats were randomly divided into conjugate groups,parathyroid hormone group,model control group and sham operation group.Serum and gut serotonin levels were tested by HPLC after 35 days of administration,and the antiosteoporosis activity of the heterocyclic oleanolic acid derivatives-aspirin conjugates was evaluated by using osteoblast-like cells isolated from murine calvaria by MTT assay.Results The preliminary biological results showed that heterocyclic oleanolic acid derivatives-aspirin conjugates displayed a dose-dependent suppression on TPH-1 in RBL-2H3,and the inhibition rate was 20.4%-92.5%.Specifically,conjugate 7 at 10 μmol·L-1 concentration showed the greatest inhibition rate on TPH-1 (92.5%).Content of TPH-1 was 51 ng mL-1,significantly lower than that in the control group (216 ng·mL-1),as well as the TPH-1 mRNA.Compared with the sham operation group,levels of serum and gut serotonin were increased in OVX group,while they were significanlty decreased in conjugate groups,and reduced significantly in conjugate 7 group (232 and 155 ng·mL-1) as compared with OVX group (1 050 and 783 ng·mL-1);Moreover,heterocyclic oleanolic acid derivatives-aspirin conjugates could increase the bone formation.Conclusion This study provides information and basis for development of novel,efficient and harmfulless oleanolic acid derivatives with anti-osteoporosis.
