<i>Swertiamarin</i> Rescues 3-NPA-Induced Defective Follicular Development via Modulating the NRF2/HO-1 Signaling Pathway in Granulosa Cells
The normal development of ovarian follicles, characterized by oocyte growth and granulosa cell proliferation, is essential for maintaining female fertility. Elevated oxidative stress, resulting from various in vivo and in vitro factors, significantly impairs follicular development, ovulation, and ov...
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2025-06-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/14/7/794 |
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| author | Luoyu Mo Gan Yang Dongju Liu Huai Zhang Xiaodong Dong Fuyong Li Ziqian Huang Dini Zhang Yan Xiong Xianrong Xiong Honghong He Jian Li Shi Yin |
| author_facet | Luoyu Mo Gan Yang Dongju Liu Huai Zhang Xiaodong Dong Fuyong Li Ziqian Huang Dini Zhang Yan Xiong Xianrong Xiong Honghong He Jian Li Shi Yin |
| author_sort | Luoyu Mo |
| collection | DOAJ |
| description | The normal development of ovarian follicles, characterized by oocyte growth and granulosa cell proliferation, is essential for maintaining female fertility. Elevated oxidative stress, resulting from various in vivo and in vitro factors, significantly impairs follicular development, ovulation, and overall female fertility. <i>Swertiamarin</i>, a naturally occurring iridoid terpenoid compound, exhibits multiple beneficial properties, including anti-hyperlipidemic, anti-diabetic, and antioxidant effects. This study investigates the impact of <i>Swertiamarin</i> on follicular development impairment induced by oxidative stress, using the commonly applied oxidant 3-nitrophthalic acid (3-NPA) in a murine model. Our findings indicate that <i>Swertiamarin</i> administration mitigates the adverse effects of 3-NPA on follicular development and ovulation. Further analyses reveal that <i>Swertiamarin</i> treatment partially enhances granulosa cell proliferation and inhibits apoptosis under oxidative stress in vivo and in vitro. Moreover, <i>Swertiamarin</i> reduces oxidative stress in ovaries and granulosa cells exposed to 3-NPA. The expression levels of key members of the NRF2/HO-1 signaling pathway, including nuclear factor erythroid 2-related factor 2 (<i>Nrf2</i>), heme oxygenase 1 (<i>Ho-1</i>), and superoxide dismutase 1 (<i>Sod1</i>), were upregulated following <i>Swertiamarin</i> supplementation in 3-NPA-treated ovaries and granulosa cells. In conclusion, the present study demonstrates that <i>Swertiamarin</i> can partially restore defective follicular development induced by oxidative stress via modulating the NRF2/HO-1 pathway in granulosa cells. These findings provide novel insights into the potential application of <i>Swertiamarin</i> in enhancing female reproductive health and offer a promising strategy for addressing reproductive damage caused by oxidative stress. |
| format | Article |
| id | doaj-art-297fddeb4460425f98af75df3c5391f4 |
| institution | Kabale University |
| issn | 2076-3921 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj-art-297fddeb4460425f98af75df3c5391f42025-08-20T03:36:11ZengMDPI AGAntioxidants2076-39212025-06-0114779410.3390/antiox14070794<i>Swertiamarin</i> Rescues 3-NPA-Induced Defective Follicular Development via Modulating the NRF2/HO-1 Signaling Pathway in Granulosa CellsLuoyu Mo0Gan Yang1Dongju Liu2Huai Zhang3Xiaodong Dong4Fuyong Li5Ziqian Huang6Dini Zhang7Yan Xiong8Xianrong Xiong9Honghong He10Jian Li11Shi Yin12College of Animal & Veterinary Sciences, Southwest Minzu University, Chengdu 610041, ChinaCollege of Animal & Veterinary Sciences, Southwest Minzu University, Chengdu 610041, ChinaCollege of Animal & Veterinary Sciences, Southwest Minzu University, Chengdu 610041, ChinaCollege of Animal & Veterinary Sciences, Southwest Minzu University, Chengdu 610041, ChinaCollege of Animal & Veterinary Sciences, Southwest Minzu University, Chengdu 610041, ChinaCollege of Animal & Veterinary Sciences, Southwest Minzu University, Chengdu 610041, ChinaCollege of Animal & Veterinary Sciences, Southwest Minzu University, Chengdu 610041, ChinaCollege of Animal & Veterinary Sciences, Southwest Minzu University, Chengdu 610041, ChinaCollege of Animal & Veterinary Sciences, Southwest Minzu University, Chengdu 610041, ChinaCollege of Animal & Veterinary Sciences, Southwest Minzu University, Chengdu 610041, ChinaCollege of Animal & Veterinary Sciences, Southwest Minzu University, Chengdu 610041, ChinaCollege of Animal & Veterinary Sciences, Southwest Minzu University, Chengdu 610041, ChinaCollege of Animal & Veterinary Sciences, Southwest Minzu University, Chengdu 610041, ChinaThe normal development of ovarian follicles, characterized by oocyte growth and granulosa cell proliferation, is essential for maintaining female fertility. Elevated oxidative stress, resulting from various in vivo and in vitro factors, significantly impairs follicular development, ovulation, and overall female fertility. <i>Swertiamarin</i>, a naturally occurring iridoid terpenoid compound, exhibits multiple beneficial properties, including anti-hyperlipidemic, anti-diabetic, and antioxidant effects. This study investigates the impact of <i>Swertiamarin</i> on follicular development impairment induced by oxidative stress, using the commonly applied oxidant 3-nitrophthalic acid (3-NPA) in a murine model. Our findings indicate that <i>Swertiamarin</i> administration mitigates the adverse effects of 3-NPA on follicular development and ovulation. Further analyses reveal that <i>Swertiamarin</i> treatment partially enhances granulosa cell proliferation and inhibits apoptosis under oxidative stress in vivo and in vitro. Moreover, <i>Swertiamarin</i> reduces oxidative stress in ovaries and granulosa cells exposed to 3-NPA. The expression levels of key members of the NRF2/HO-1 signaling pathway, including nuclear factor erythroid 2-related factor 2 (<i>Nrf2</i>), heme oxygenase 1 (<i>Ho-1</i>), and superoxide dismutase 1 (<i>Sod1</i>), were upregulated following <i>Swertiamarin</i> supplementation in 3-NPA-treated ovaries and granulosa cells. In conclusion, the present study demonstrates that <i>Swertiamarin</i> can partially restore defective follicular development induced by oxidative stress via modulating the NRF2/HO-1 pathway in granulosa cells. These findings provide novel insights into the potential application of <i>Swertiamarin</i> in enhancing female reproductive health and offer a promising strategy for addressing reproductive damage caused by oxidative stress.https://www.mdpi.com/2076-3921/14/7/794<i>Swertiamarin</i>oxidative stressfollicle developmentgranulosa cellNRF2/HO-1 pathway |
| spellingShingle | Luoyu Mo Gan Yang Dongju Liu Huai Zhang Xiaodong Dong Fuyong Li Ziqian Huang Dini Zhang Yan Xiong Xianrong Xiong Honghong He Jian Li Shi Yin <i>Swertiamarin</i> Rescues 3-NPA-Induced Defective Follicular Development via Modulating the NRF2/HO-1 Signaling Pathway in Granulosa Cells Antioxidants <i>Swertiamarin</i> oxidative stress follicle development granulosa cell NRF2/HO-1 pathway |
| title | <i>Swertiamarin</i> Rescues 3-NPA-Induced Defective Follicular Development via Modulating the NRF2/HO-1 Signaling Pathway in Granulosa Cells |
| title_full | <i>Swertiamarin</i> Rescues 3-NPA-Induced Defective Follicular Development via Modulating the NRF2/HO-1 Signaling Pathway in Granulosa Cells |
| title_fullStr | <i>Swertiamarin</i> Rescues 3-NPA-Induced Defective Follicular Development via Modulating the NRF2/HO-1 Signaling Pathway in Granulosa Cells |
| title_full_unstemmed | <i>Swertiamarin</i> Rescues 3-NPA-Induced Defective Follicular Development via Modulating the NRF2/HO-1 Signaling Pathway in Granulosa Cells |
| title_short | <i>Swertiamarin</i> Rescues 3-NPA-Induced Defective Follicular Development via Modulating the NRF2/HO-1 Signaling Pathway in Granulosa Cells |
| title_sort | i swertiamarin i rescues 3 npa induced defective follicular development via modulating the nrf2 ho 1 signaling pathway in granulosa cells |
| topic | <i>Swertiamarin</i> oxidative stress follicle development granulosa cell NRF2/HO-1 pathway |
| url | https://www.mdpi.com/2076-3921/14/7/794 |
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