Kurarinone attenuates hydrogen peroxide‐induced oxidative stress and apoptosis through activating the PI3K/Akt signaling by upregulating IGF1 expression in human ovarian granulosa cells

• DOI: 10.1002/tox.23659
• Publication Date: 2022-09-17T11:24:25Z
• Authors: Weiwei Li; Xiurong Yin; Yani Yan; Cong Liu; Gang Li
• Keywords: 0303 health sciences; Granulosa Cells; Follicular Atresia; Apoptosis; Hydrogen Peroxide; 3. Good health; Phosphatidylinositol 3-Kinases; Oxidative Stress; 03 medical and health sciences; Humans; Female; Insulin-Like Growth Factor I; Reactive Oxygen Species; Proto-Oncogene Proteins c-akt; Signal Transduction

AbstractDysregulated follicular development may lead to follicular atresia, and this is associated with oxidative stress in granulosa cells. Kurarinone is a natural compound possessing multiple activities, including antioxidative ability. However, the role of kurarinone in granulosa cell damage during follicular atresia remains unknown. Human ovarian granulosa KGN cells were treated with hydrogen peroxide (H2O2) to induce cellular damage. Cytotoxicity was investigated by lactate dehydrogenase (LDH) release assay. Oxidative stress was evaluated by detection of reactive oxygen species (ROS) generation and oxidative biomarker levels. Cell apoptosis was evaluated by flow cytometry, a Cell Death Detection ELISA Kit, and a Caspase‐3 Assay Kit. The downstream target and related signaling pathway were analyzed by western blotting. Kurarinone attenuated H2O2‐induced LDH release in KGN cells. Kurarinone relieved H2O2‐induced increase in ROS generation and malondialdehyde level as well as decrease in superoxide dismutase‐1 activity and heme oxygenase 1 and NAD(P)H quinone dehydrogenase 1 mRNA levels. Kurarinone inhibited H2O2‐induced apoptosis in KGN cells. Kurarinone targeted insulin‐like growth factor 1 (IGF1) and upregulated IGF1 expression to activate the phosphatidylinositol 3‐kinase (PI3K)/protein kinase B (Akt) signaling. IGF1 silencing attenuated the suppressive effects of kurarinone on H2O2‐induced oxidative stress and apoptosis in KGN cells. In conclusion, kurarinone attenuates H2O2‐induced oxidative stress and apoptosis in KGN cells through activating the PI3K/Akt signaling by upregulating IGF1 expression, indicating the therapeutic potential of kurarinone in follicular atresia.