Stachydrine Protects Against Cyclophosphamide‐Induced Premature Ovarian Insufficiency in Wistar Rats by Inhibiting Oxidative Stress and Apoptosis via the Activation of the Nrf2/HO‐1 Signalling Pathway

Excessive oxidative stress and apoptosis of ovarian granulosa cells lead to severe ovarian dysfunctions and even premature ovarian insufficiency (POI). Stachydrine (STA), the main active component of Leonurus japonicas, possesses antioxidant and anti-apoptotic actions. However, the effects of STA on POI remain unknown. This work aimed to investigate STA's role in cyclophosphamide (CP)-induced POI. CP was intraperitoneally injected into rats for 14 days (200 mg/kg for day 1, 8 mg/kg for day 2–14) to establish a POI model, and STA (20 or 40 mg/kg/d) was orally given to rats for three weeks after CP treatment. We found that STA treatment (40 mg/kg) alleviated the estrous cycle disorder and the imbalance of serum sex hormone levels in CP-treated rats. Further, STA administration (40 mg/kg) inhibited oxidative stress and apoptosis of ovarian granulosa cells. Subsequently, human granulosa-like cells (KGN) were treated with CP (250 μM) for 48 h, followed by STA administration (1 μM) for 24 h to investigate the in vitro effects of STA. Consistently, STA treatment prevented KGN cells from CP-induced cell damage. In detail, STA treatment activated the Nrf2/HO-1 signalling pathway, thereby inhibiting the oxidative stress and cell apoptosis of CP-injured KGN cells. In conclusion, STA exerted a protective role in CP-induced POI by alleviating oxidative stress and apoptosis through activating the Nrf2/HO-1 signalling pathway, providing a new insight into POI treatment. Conflicts of Interest The authors declare no conflicts of interest. Data Availability Statement The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request. Peer Review The peer review history for this article is available at https://www.webofscience.com/api/gateway/wos/peer-review/10.1111/1440-1681.70052. Supporting Information | Filename | Description | |---|---| | cep70052-sup-0001-supinfo.tifTIFF image, 2 MB | Figure S1. Original uncropped images of western blot assays. | Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

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