# Ginseng Polysaccharides Protect Against Endoplasmic Reticulum Stress-Induced Damage via PI3K/Akt Signalling Pathway in Bovine Ovarian Granulosa Cells

## TL;DR

Ginseng polysaccharides protect bovine ovarian cells from stress-induced damage by activating a key signaling pathway, potentially improving fertility in cattle.

## Contribution

This study reveals a novel mechanism by which ginseng polysaccharides protect granulosa cells via the PI3K/Akt pathway and inhibition of necroptosis.

## Key findings

- Ginseng polysaccharides alleviate endoplasmic reticulum stress and necroptosis in bovine granulosa cells.
- Activation of the PI3K/Akt pathway is crucial for the protective effects of ginseng polysaccharides.
- In vivo experiments confirm that ginseng polysaccharides reduce ovarian damage in mice.

## Abstract

What are the main findings?
Ginseng polysaccharides protect ovarian granulosa cells by alleviating endoplasmic reticulum stress and inhibiting subsequent necroptosis via the RIPK3/MLKL pathway.The polysaccharides restore cellular proliferation and estrogen synthesis compromised by ERS, primarily through activation of the PI3K/Akt signalling pathway, a mechanism corroborated by in vivo studies.

Ginseng polysaccharides protect ovarian granulosa cells by alleviating endoplasmic reticulum stress and inhibiting subsequent necroptosis via the RIPK3/MLKL pathway.

The polysaccharides restore cellular proliferation and estrogen synthesis compromised by ERS, primarily through activation of the PI3K/Akt signalling pathway, a mechanism corroborated by in vivo studies.

What are the implications of the main findings?
The study identifies ginseng polysaccharides as a promising natural agent for protecting ovarian function, offering a potential preventive or therapeutic strategy against ovarian disorders driven by endoplasmic reticulum stress and necroptosis, such as premature ovarian insufficiency.It establishes a clear molecular pathway where these polysaccharides alleviate ER stress, inhibit the downstream RIPK3/MLKL-mediated necroptosis, and activate pro-survival PI3K/Akt signalling to restore cell health, providing a validated target for future interventions.

The study identifies ginseng polysaccharides as a promising natural agent for protecting ovarian function, offering a potential preventive or therapeutic strategy against ovarian disorders driven by endoplasmic reticulum stress and necroptosis, such as premature ovarian insufficiency.

It establishes a clear molecular pathway where these polysaccharides alleviate ER stress, inhibit the downstream RIPK3/MLKL-mediated necroptosis, and activate pro-survival PI3K/Akt signalling to restore cell health, providing a validated target for future interventions.

Necroptosis and dysfunction of ovarian granulosa cells are major contributors to follicular atresia and reduced fertility in cattle, processes that are closely associated with endoplasmic reticulum stress (ERS). Ginseng polysaccharides (GPSs) are known to reduce ER stress, display anti-inflammatory properties, and modulate reproductive function; however, whether GPS can protect against granulosa cell injury and the underlying mechanisms remain unclear. To address this gap, this study aimed to investigate the protective effects of GPS on ERS-induced bovine granulosa cell damage and to elucidate the associated mechanisms. An ERS model was established in bovine granulosa cells using tunicamycin (Tm), and cellular responses were evaluated via flow cytometry, ELISA, and EdU assays. Further, a mouse model was used to validate the protective effects of GPS against Tm-induced ovarian injury. The results showed that 40 μg/mL of GPS significantly alleviated ERS-induced granulosa cell damage, inhibited necroptosis, and mitigated ERS. Moreover, using the PI3K/Akt pathway inhibitor LY294002, we demonstrated that the inhibitor antagonized the effects of GPS, indicating that GPS promotes granulosa cell proliferation and restores estrogen secretion via activating the PI3K/Akt pathway. In vivo experiments further confirmed that GPS effectively attenuates ERS-induced ovarian damage in mice. Collectively, these findings reveal that GPS improves granulosa cell function and ovarian tissue integrity by modulating the ERS network and the PI3K/Akt pathway, yielding a theoretical basis for preventing follicular atresia and enhancing reproductive efficiency in cattle.