Puerarin Ameliorates the Ferroptosis in Diabetic Liver Injure Through the JAK2/STAT3 Pathway Inhibition Based on Network Pharmacology and Experimental Validation
Xiaoxu Fan,1 Shuangqiao Liu,1 Jing Yu,2 Jian Hua,1 Yingtong Feng,1 Zhen Wang,1 Yiwei Shen,1 Wei Lan,2 Jingxia Wang1 1School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 2School of Traditional Chinese Medicine, Xinjiang Medical Universi...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Dove Medical Press
2025-02-01
|
| Series: | Drug Design, Development and Therapy |
| Subjects: | |
| Online Access: | https://www.dovepress.com/puerarin-ameliorates-the-ferroptosis-in-diabetic-liver-injure-through--peer-reviewed-fulltext-article-DDDT |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832570230405070848 |
|---|---|
| author | Fan X Liu S Yu J Hua J Feng Y Wang Z Shen Y Lan W Wang J |
| author_facet | Fan X Liu S Yu J Hua J Feng Y Wang Z Shen Y Lan W Wang J |
| author_sort | Fan X |
| collection | DOAJ |
| description | Xiaoxu Fan,1 Shuangqiao Liu,1 Jing Yu,2 Jian Hua,1 Yingtong Feng,1 Zhen Wang,1 Yiwei Shen,1 Wei Lan,2 Jingxia Wang1 1School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 2School of Traditional Chinese Medicine, Xinjiang Medical University, Urumqi, People’s Republic of ChinaCorrespondence: Jingxia Wang, School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, People’s Republic of China, Email 601435@bucm.edu.cn Wei Lan, School of Traditional Chinese Medicine, Xinjiang Medical University, Urumqi, People’s Republic of China, Email lanwei516@sina.comBackground: Diabetic liver injury (DLI) is a common complication of diabetes mellitus (DM), which seriously endangers the health of diabetic patients. Puerarin, the main active component of Pueraria lobata, has shown positive effects in lowering blood glucose and lipids, resisting oxidative stress, and protecting the liver. However, the mechanism of protective effect of Puerarin on DLI remains unclear.Methods: Various databases were used to screen for targets of Puerarin, ferroptosis and DLI. Protein-protein interaction (PPI) network and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were used to predict key targets and pathways. Molecular docking was used to predict the interactions between Puerarin and core targets. KK/Upj-Ay/J (KKAy) mice and high glucose (HG)-induced AML12 cells were used to study the protective effect of Puerarin on DLI. The molecular mechanisms by which Puerarin acts were further verified by in vivo and in vitro experiments.Results: KEGG analysis indicated that the JAK/STAT pathway might be related to the anti-DLI effect of Puerarin. Molecular docking revealed that Puerarin has good affinity for JAK2 and STAT3. In vivo, Puerarin (80 mg/kg) reduced body weight, blood glucose, blood lipids and liver function in KKAy mice fed a high-sugar, high-fat diet. Puerarin also ameliorated hepatic pathological changes and inflammatory responses, and attenuated oxidative stress and iron overload in KKAy mice. Western blotting results showed that Puerarin could regulate the expression of proteins related to JAK2/STAT3 pathway and ferroptosis pathway. In vitro, Puerarin (25, 50, 100 μM) increased cell viability and decreased steatosis and liver function indexes in AML12 cells induced by HG (30 mm) to varying degrees. More importantly, AG490 blocker experiments showed that the regulation of ferroptosis process by Puerarin was dependent on the JAK2/STAT3 pathway.Conclusion: In conclusion, this study revealed Puerarin may regulate the ferroptosis process by inhibiting the JAK2/STAT3 pathway for the treatment of DLI. Keywords: puerarin, diabetic liver injury, ferroptosis, JAK2/STAT3 pathway, network pharmacology |
| format | Article |
| id | doaj-art-a79ced336ba64293a0890222c218a539 |
| institution | Kabale University |
| issn | 1177-8881 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Drug Design, Development and Therapy |
| spelling | doaj-art-a79ced336ba64293a0890222c218a5392025-02-02T15:59:40ZengDove Medical PressDrug Design, Development and Therapy1177-88812025-02-01Volume 1973775799808Puerarin Ameliorates the Ferroptosis in Diabetic Liver Injure Through the JAK2/STAT3 Pathway Inhibition Based on Network Pharmacology and Experimental ValidationFan XLiu SYu JHua JFeng YWang ZShen YLan WWang JXiaoxu Fan,1 Shuangqiao Liu,1 Jing Yu,2 Jian Hua,1 Yingtong Feng,1 Zhen Wang,1 Yiwei Shen,1 Wei Lan,2 Jingxia Wang1 1School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 2School of Traditional Chinese Medicine, Xinjiang Medical University, Urumqi, People’s Republic of ChinaCorrespondence: Jingxia Wang, School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, People’s Republic of China, Email 601435@bucm.edu.cn Wei Lan, School of Traditional Chinese Medicine, Xinjiang Medical University, Urumqi, People’s Republic of China, Email lanwei516@sina.comBackground: Diabetic liver injury (DLI) is a common complication of diabetes mellitus (DM), which seriously endangers the health of diabetic patients. Puerarin, the main active component of Pueraria lobata, has shown positive effects in lowering blood glucose and lipids, resisting oxidative stress, and protecting the liver. However, the mechanism of protective effect of Puerarin on DLI remains unclear.Methods: Various databases were used to screen for targets of Puerarin, ferroptosis and DLI. Protein-protein interaction (PPI) network and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were used to predict key targets and pathways. Molecular docking was used to predict the interactions between Puerarin and core targets. KK/Upj-Ay/J (KKAy) mice and high glucose (HG)-induced AML12 cells were used to study the protective effect of Puerarin on DLI. The molecular mechanisms by which Puerarin acts were further verified by in vivo and in vitro experiments.Results: KEGG analysis indicated that the JAK/STAT pathway might be related to the anti-DLI effect of Puerarin. Molecular docking revealed that Puerarin has good affinity for JAK2 and STAT3. In vivo, Puerarin (80 mg/kg) reduced body weight, blood glucose, blood lipids and liver function in KKAy mice fed a high-sugar, high-fat diet. Puerarin also ameliorated hepatic pathological changes and inflammatory responses, and attenuated oxidative stress and iron overload in KKAy mice. Western blotting results showed that Puerarin could regulate the expression of proteins related to JAK2/STAT3 pathway and ferroptosis pathway. In vitro, Puerarin (25, 50, 100 μM) increased cell viability and decreased steatosis and liver function indexes in AML12 cells induced by HG (30 mm) to varying degrees. More importantly, AG490 blocker experiments showed that the regulation of ferroptosis process by Puerarin was dependent on the JAK2/STAT3 pathway.Conclusion: In conclusion, this study revealed Puerarin may regulate the ferroptosis process by inhibiting the JAK2/STAT3 pathway for the treatment of DLI. Keywords: puerarin, diabetic liver injury, ferroptosis, JAK2/STAT3 pathway, network pharmacologyhttps://www.dovepress.com/puerarin-ameliorates-the-ferroptosis-in-diabetic-liver-injure-through--peer-reviewed-fulltext-article-DDDTpuerarindiabetic liver injuryferroptosisjak2/stat3 pathwaynetwork pharmacology |
| spellingShingle | Fan X Liu S Yu J Hua J Feng Y Wang Z Shen Y Lan W Wang J Puerarin Ameliorates the Ferroptosis in Diabetic Liver Injure Through the JAK2/STAT3 Pathway Inhibition Based on Network Pharmacology and Experimental Validation Drug Design, Development and Therapy puerarin diabetic liver injury ferroptosis jak2/stat3 pathway network pharmacology |
| title | Puerarin Ameliorates the Ferroptosis in Diabetic Liver Injure Through the JAK2/STAT3 Pathway Inhibition Based on Network Pharmacology and Experimental Validation |
| title_full | Puerarin Ameliorates the Ferroptosis in Diabetic Liver Injure Through the JAK2/STAT3 Pathway Inhibition Based on Network Pharmacology and Experimental Validation |
| title_fullStr | Puerarin Ameliorates the Ferroptosis in Diabetic Liver Injure Through the JAK2/STAT3 Pathway Inhibition Based on Network Pharmacology and Experimental Validation |
| title_full_unstemmed | Puerarin Ameliorates the Ferroptosis in Diabetic Liver Injure Through the JAK2/STAT3 Pathway Inhibition Based on Network Pharmacology and Experimental Validation |
| title_short | Puerarin Ameliorates the Ferroptosis in Diabetic Liver Injure Through the JAK2/STAT3 Pathway Inhibition Based on Network Pharmacology and Experimental Validation |
| title_sort | puerarin ameliorates the ferroptosis in diabetic liver injure through the jak2 stat3 pathway inhibition based on network pharmacology and experimental validation |
| topic | puerarin diabetic liver injury ferroptosis jak2/stat3 pathway network pharmacology |
| url | https://www.dovepress.com/puerarin-ameliorates-the-ferroptosis-in-diabetic-liver-injure-through--peer-reviewed-fulltext-article-DDDT |
| work_keys_str_mv | AT fanx puerarinamelioratestheferroptosisindiabeticliverinjurethroughthejak2stat3pathwayinhibitionbasedonnetworkpharmacologyandexperimentalvalidation AT lius puerarinamelioratestheferroptosisindiabeticliverinjurethroughthejak2stat3pathwayinhibitionbasedonnetworkpharmacologyandexperimentalvalidation AT yuj puerarinamelioratestheferroptosisindiabeticliverinjurethroughthejak2stat3pathwayinhibitionbasedonnetworkpharmacologyandexperimentalvalidation AT huaj puerarinamelioratestheferroptosisindiabeticliverinjurethroughthejak2stat3pathwayinhibitionbasedonnetworkpharmacologyandexperimentalvalidation AT fengy puerarinamelioratestheferroptosisindiabeticliverinjurethroughthejak2stat3pathwayinhibitionbasedonnetworkpharmacologyandexperimentalvalidation AT wangz puerarinamelioratestheferroptosisindiabeticliverinjurethroughthejak2stat3pathwayinhibitionbasedonnetworkpharmacologyandexperimentalvalidation AT sheny puerarinamelioratestheferroptosisindiabeticliverinjurethroughthejak2stat3pathwayinhibitionbasedonnetworkpharmacologyandexperimentalvalidation AT lanw puerarinamelioratestheferroptosisindiabeticliverinjurethroughthejak2stat3pathwayinhibitionbasedonnetworkpharmacologyandexperimentalvalidation AT wangj puerarinamelioratestheferroptosisindiabeticliverinjurethroughthejak2stat3pathwayinhibitionbasedonnetworkpharmacologyandexperimentalvalidation |