Catalpol Ameliorates Premature Ovarian Failure (POF) through Activation of Inositol-requiring Enzyme 1 Pathway
Abstract:
Objective: This study was aimed at exploring the anti- premature ovarian failure (POF) mechanism of catalpol on a rat POF model.
Methods: In this study, female Sprague Dawley rats (n=48, 9- week- old) were randomly divided into control, catalpol, tripterygium glycosides (TG), and TG + catalpol groups. POF model was established by TG (75 mg/kg) intraperitoneally injection for 4 weeks. Catalpol (10 mg/kg) was intragastrically administrated to treat the progression of POF for 4 weeks. The rat serum was collected for estradiol (E2) and anti-Mullerian hormone (AMH) analysis by enzyme-linked immune sorbent assay (ELISA). The sliced rat ovaries samples were stained by hematoxylin and eosin (HE) staining. The protein levels of the inositol-requiring enzyme 1 (IRE1) pathway and related apoptosis proteins were detected by Western blot. Furthermore, the apoptosis of the ovaries was investigated by TUNEL stain.
Results: TG treated rats (POF model) decreased the secretion of E2 and AMH, up-regulated IRE1 pathway factors (heat shock 70 kDa protein 5, inositol-requiring enzyme 1α and spliced X-box binding p08rotein 1), cleaved-3 caspases and -12 caspases, and Bax expression, down-regulated bcl-2 level, induced granule cells (GCs) and granulosa lutein cells (GCLs) c damage, increased atretic follicles, and apoptosis. In contrast, catalpol apparently prevented all TG-induced changes.
Conclusions: The IRE1 pathway is involved in ovarian injuries induced by TG, but it could be prevented by catalpol treatment. Catalpol could ameliorate hormone secretion and follicular preservation in POF rats through downregulation of IRE1 pathway and its downstream apoptotic factors.
