Network pharmacology uncovers that secoisolariciresinol diglucoside ameliorate premature ovarian insufficiency via PI3K/Akt pathway
Abstract As one of the essential lignan derivative found in traditional Chinese medicinal herbs, secoisolariciresinol diglucoside (SDG) was proved to promote women’s health through its phytoestrogenic properties. Increasingly studies indicated that this compound could be a potential drug capable of...
Saved in:
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-01-01
|
| Series: | Scientific Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.1038/s41598-024-83484-3 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1841544636385984512 |
|---|---|
| author | Yiqing Zhang Xialu Liu Zitong Zheng Haiqiang Huang Yurou Wang Shuqin Wu Yuan Shu Yuxin Yang Yufei Zhong Pengfei Liao Yongsong Wang Zezheng Pan |
| author_facet | Yiqing Zhang Xialu Liu Zitong Zheng Haiqiang Huang Yurou Wang Shuqin Wu Yuan Shu Yuxin Yang Yufei Zhong Pengfei Liao Yongsong Wang Zezheng Pan |
| author_sort | Yiqing Zhang |
| collection | DOAJ |
| description | Abstract As one of the essential lignan derivative found in traditional Chinese medicinal herbs, secoisolariciresinol diglucoside (SDG) was proved to promote women’s health through its phytoestrogenic properties. Increasingly studies indicated that this compound could be a potential drug capable of preventing estrogen-related diseases. Here, we aimed to investigate whether SDG can counteract cyclophosphamide (CTX) induced premature ovarian insufficiency (POI) and further explore its specific molecular mechanism. In this study, we first validated the therapeutic effect of SDG on POI in a mouse model. Then, the mechanism by which SDG improves POI is predicted through a combination of network and pharmacology, and its authenticity is further confirmed by experimental verification, molecular docking analysis and molecular dynamics simulation. The results showed that SDG significantly alleviated POI by improving ovarian indices and follicle counts while protecting against CTX-induced ovarian damage by modulating the PI3K/Akt signaling pathway in KGN cells. In addition, molecular docking studies confirmed SDG’s high affinity for Akt1 and PI3Kγ, pinpointing the precise interaction sites. These results underscore the protective mechanisms of SDG against ovarian damage, highlighting its therapeutic potential. In summary, our study identified that SDG can ameliorate CTX-induced POI with its mechanism of action intricately linked to the modulation of the PI3K/Akt signaling pathway. |
| format | Article |
| id | doaj-art-0121a975e2d745c391cb97bab165a3fe |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-0121a975e2d745c391cb97bab165a3fe2025-01-12T12:21:58ZengNature PortfolioScientific Reports2045-23222025-01-0115111410.1038/s41598-024-83484-3Network pharmacology uncovers that secoisolariciresinol diglucoside ameliorate premature ovarian insufficiency via PI3K/Akt pathwayYiqing Zhang0Xialu Liu1Zitong Zheng2Haiqiang Huang3Yurou Wang4Shuqin Wu5Yuan Shu6Yuxin Yang7Yufei Zhong8Pengfei Liao9Yongsong Wang10Zezheng Pan11School of Basic Medical Sciences, Jiangxi Medical College, Nanchang UniversitySchool of Basic Medical Sciences, Jiangxi Medical College, Nanchang UniversitySchool of Basic Medical Sciences, Jiangxi Medical College, Nanchang UniversitySchool of Basic Medical Sciences, Jiangxi Medical College, Nanchang UniversitySchool of Basic Medical Sciences, Jiangxi Medical College, Nanchang UniversitySchool of Basic Medical Sciences, Jiangxi Medical College, Nanchang UniversitySchool of Basic Medical Sciences, Jiangxi Medical College, Nanchang UniversitySchool of Basic Medical Sciences, Jiangxi Medical College, Nanchang UniversitySchool of Basic Medical Sciences, Jiangxi Medical College, Nanchang UniversityJiangxi KingMed Clinical Laboratory CoJiangxi KingMed Clinical Laboratory CoSchool of Basic Medical Sciences, Jiangxi Medical College, Nanchang UniversityAbstract As one of the essential lignan derivative found in traditional Chinese medicinal herbs, secoisolariciresinol diglucoside (SDG) was proved to promote women’s health through its phytoestrogenic properties. Increasingly studies indicated that this compound could be a potential drug capable of preventing estrogen-related diseases. Here, we aimed to investigate whether SDG can counteract cyclophosphamide (CTX) induced premature ovarian insufficiency (POI) and further explore its specific molecular mechanism. In this study, we first validated the therapeutic effect of SDG on POI in a mouse model. Then, the mechanism by which SDG improves POI is predicted through a combination of network and pharmacology, and its authenticity is further confirmed by experimental verification, molecular docking analysis and molecular dynamics simulation. The results showed that SDG significantly alleviated POI by improving ovarian indices and follicle counts while protecting against CTX-induced ovarian damage by modulating the PI3K/Akt signaling pathway in KGN cells. In addition, molecular docking studies confirmed SDG’s high affinity for Akt1 and PI3Kγ, pinpointing the precise interaction sites. These results underscore the protective mechanisms of SDG against ovarian damage, highlighting its therapeutic potential. In summary, our study identified that SDG can ameliorate CTX-induced POI with its mechanism of action intricately linked to the modulation of the PI3K/Akt signaling pathway.https://doi.org/10.1038/s41598-024-83484-3Secoisolariciresinol diglucosidePremature ovarian insufficiencyGranulosa cellsPI3K/Akt pathwayNetwork pharmacology |
| spellingShingle | Yiqing Zhang Xialu Liu Zitong Zheng Haiqiang Huang Yurou Wang Shuqin Wu Yuan Shu Yuxin Yang Yufei Zhong Pengfei Liao Yongsong Wang Zezheng Pan Network pharmacology uncovers that secoisolariciresinol diglucoside ameliorate premature ovarian insufficiency via PI3K/Akt pathway Scientific Reports Secoisolariciresinol diglucoside Premature ovarian insufficiency Granulosa cells PI3K/Akt pathway Network pharmacology |
| title | Network pharmacology uncovers that secoisolariciresinol diglucoside ameliorate premature ovarian insufficiency via PI3K/Akt pathway |
| title_full | Network pharmacology uncovers that secoisolariciresinol diglucoside ameliorate premature ovarian insufficiency via PI3K/Akt pathway |
| title_fullStr | Network pharmacology uncovers that secoisolariciresinol diglucoside ameliorate premature ovarian insufficiency via PI3K/Akt pathway |
| title_full_unstemmed | Network pharmacology uncovers that secoisolariciresinol diglucoside ameliorate premature ovarian insufficiency via PI3K/Akt pathway |
| title_short | Network pharmacology uncovers that secoisolariciresinol diglucoside ameliorate premature ovarian insufficiency via PI3K/Akt pathway |
| title_sort | network pharmacology uncovers that secoisolariciresinol diglucoside ameliorate premature ovarian insufficiency via pi3k akt pathway |
| topic | Secoisolariciresinol diglucoside Premature ovarian insufficiency Granulosa cells PI3K/Akt pathway Network pharmacology |
| url | https://doi.org/10.1038/s41598-024-83484-3 |
| work_keys_str_mv | AT yiqingzhang networkpharmacologyuncoversthatsecoisolariciresinoldiglucosideameliorateprematureovarianinsufficiencyviapi3kaktpathway AT xialuliu networkpharmacologyuncoversthatsecoisolariciresinoldiglucosideameliorateprematureovarianinsufficiencyviapi3kaktpathway AT zitongzheng networkpharmacologyuncoversthatsecoisolariciresinoldiglucosideameliorateprematureovarianinsufficiencyviapi3kaktpathway AT haiqianghuang networkpharmacologyuncoversthatsecoisolariciresinoldiglucosideameliorateprematureovarianinsufficiencyviapi3kaktpathway AT yurouwang networkpharmacologyuncoversthatsecoisolariciresinoldiglucosideameliorateprematureovarianinsufficiencyviapi3kaktpathway AT shuqinwu networkpharmacologyuncoversthatsecoisolariciresinoldiglucosideameliorateprematureovarianinsufficiencyviapi3kaktpathway AT yuanshu networkpharmacologyuncoversthatsecoisolariciresinoldiglucosideameliorateprematureovarianinsufficiencyviapi3kaktpathway AT yuxinyang networkpharmacologyuncoversthatsecoisolariciresinoldiglucosideameliorateprematureovarianinsufficiencyviapi3kaktpathway AT yufeizhong networkpharmacologyuncoversthatsecoisolariciresinoldiglucosideameliorateprematureovarianinsufficiencyviapi3kaktpathway AT pengfeiliao networkpharmacologyuncoversthatsecoisolariciresinoldiglucosideameliorateprematureovarianinsufficiencyviapi3kaktpathway AT yongsongwang networkpharmacologyuncoversthatsecoisolariciresinoldiglucosideameliorateprematureovarianinsufficiencyviapi3kaktpathway AT zezhengpan networkpharmacologyuncoversthatsecoisolariciresinoldiglucosideameliorateprematureovarianinsufficiencyviapi3kaktpathway |