Ameliorative effect of salidroside on the cyclophosphamide-induced premature ovarian failure in a rat model

Abstract

Background

Oxidative stress injury is an important pathological factor of premature ovarian failure (POF). Salidroside, extracted from the Chinese herb-Rhodiola rosea, has advantages in antioxidant characteristics. However, their therapeutic efficacy and mechanisms in POF have not been explored.

Purpose

This study aims to assess the therapeutic effects of salidroside in chemotherapy-induced ovarian failure rats.

Methods

A POF rat model was established by injection of cyclophosphamide, followed by treatment with salidroside. The therapeutic effect of salidroside was evaluated based on hormone levels, follicle count, and reproductive ability. Oxidative stress injury was assessed by the detection of SOD enzyme activity and MDA levels. Differential gene expression of Keap1, Nrf2, HMOX1, NQO1, AMH, BMP15, and GDF9, were identified by qRT‑PCR. The protein expression of Keap1, Nrf2, P53, and Bcl-2 were detected by western blot.

Results

Salidroside treatment markedly restored FSH, E2, and AMH hormone secretion levels, reduced follicular atresia, and increased antral follicle numbers in POF rats. In addition, salidroside improves fertility in POF rats, activates the Nrf2 signaling pathway, and reduces the level of oxidative stress. The recovery function of high dose salidroside (50 mg/kg) in a reproductive assay was significantly improved than that of lower dose salidroside (25 mg/kg). Meanwhile, the safety evaluation of salidroside treatment in rats showed that salidroside was safe for POF rats at doses of 25–50 mg/kg.

Conclusions

Salidroside therapy improved premature ovarian failure significantly through antioxidant function and activating Nrf2 signaling.

Keywords:

• salidroside
• premature ovarian failure (POF)
• oxidative stress injury
• antioxidant activity
• Nrf2 signaling

Author contributions

Lixuan Chen and Qinglin Mo contributed equally to this work. Yang Xiao and KaiXian Deng were mainly responsible for project design, and the acquisition of financial support. The experiments in rats were performed by Lixuan Chen and Yinnang Wu. Wancheng Chen and Qinglin Mo mainly assisted in the completion of experiments, and proofread the article. The manuscript was written by Lixuan Chen.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This research was supported by the Foshan Municipal Science and Technology Bureau 2020 Foshan Municipal Science and Technology Research Project (Grant No. 2020001006077), Special Funding Fund for Clinical Scientific Research of Wu Jieping Medical Foundation (Grant No. 320.6750.2021-04-43), and the Regional Joint Fund of Basic and Applied basic Research Fund of Guangdong Province (Grant No. 2019B151520082).