# Metabolomics Analysis on the Effect of Cucumaria frondosa Tentacles Hydrolysates on Cyclophosphamide-Induced Premature Ovarian Insufficiency

## TL;DR

This study explores how Cucumaria frondosa tentacles hydrolysates may help treat premature ovarian insufficiency in mice by reducing cell death and oxidative stress.

## Contribution

The study introduces CFTH as a potential therapeutic for POI through metabolomics and mechanistic analysis in a mouse model.

## Key findings

- CFTH reversed estrous cycle dysregulation and hormone imbalances in POI mice.
- CFTH reduced granulosa cell apoptosis and modulated apoptosis-related gene expression.
- Metabolomics suggests CFTH improves ovarian function via steroid biosynthesis and cGMP-PKG signaling.

## Abstract

Background: Premature ovarian insufficiency (POI) poses a significant challenge for women. The effects of Cucumaria frondosa tentacles hydrolysates (CFTH) on POI remain to be fully elucidated. Purpose: This study aimed to determine whether CFTH exerts a beneficial effect on ovarian function using a POI mouse model and to investigate the underlying mechanisms of action. Methods: In this study, we characterized the amino acid composition and physicochemical properties of CFTH. The POI model was established by administering 100 mg/kg of cyclophosphamide (CP). We assessed the regulation of the estrous cycle, hormone levels, ovarian cell apoptosis, and oxidative stress markers in POI mice. Differences in ovarian and uterine morphology among the different groups were observed. Furthermore, metabolomics analysis was employed to explore potential mechanisms. Results: CFTH treatment reversed the dysregulation of the estrous cycle and hormone levels. TUNEL analysis revealed that CFTH treatment significantly reduced apoptosis in granulosa cells and altered the expression levels of apoptosis-related genes at the mRNA level. Additionally, CFTH significantly increased superoxide dismutase activity and decreased malondialdehyde levels, thereby mitigating oxidative stress. Metabolomics analysis suggested that CFTH may ameliorate ovarian dysfunction by regulating steroid biosynthesis and the cGMP-PKG signaling pathway. Conclusions: These findings suggest that CFTH may serve as an effective strategy for alleviating POI. Further research is warranted to verify the long-term safety and effectiveness of CFTH in humans.