Ginkgolide B attenuates hyperlipidemia by restoring sphingolipid homeostasis and activating PPARα and Nrf2 pathways
Abstract Although hyperlipidemia is a key factor in cardiovascular disease, there are limited safe and effective therapies for disorders of lipid metabolism. This study investigated the therapeutic potential of Ginkgolide B (GB), a bioactive component of Ginkgo biloba leaves, in ameliorating hyperli...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-08-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-025-14626-4 |
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| author | Yun Liu Feng Wang Hengyu Xu Hongxin Wang Meili Lu Lan Cheng |
| author_facet | Yun Liu Feng Wang Hengyu Xu Hongxin Wang Meili Lu Lan Cheng |
| author_sort | Yun Liu |
| collection | DOAJ |
| description | Abstract Although hyperlipidemia is a key factor in cardiovascular disease, there are limited safe and effective therapies for disorders of lipid metabolism. This study investigated the therapeutic potential of Ginkgolide B (GB), a bioactive component of Ginkgo biloba leaves, in ameliorating hyperlipidemia and explored its underlying mechanisms. Utilizing a high-fat diet-induced hyperlipidemic rat model and lipidomics analysis, the study showed that GB significantly decreased serum total cholesterol, triglyceride, and low-density lipoprotein levels. Lipidomics revealed that GB reversed dysregulated sphingolipid metabolism, notably decreasing ceramides levels and increasing sphingomyelins, which are implicated in metabolic inflammation and oxidative stress. Mechanistically, GB activated PPARα, thereby enhancing fatty acid oxidation and upregulating the Nrf2 pathway to mitigate oxidative damage. These dual effects were validated in vitro using HepG2 cells, where GB reduced lipid accumulation and improved antioxidant defenses. Overall, these findings highlight GB as a promising therapeutic agent for hyperlipidemia by restoring sphingolipid homeostasis and targeting the interplay between lipid metabolism and oxidative stress. |
| format | Article |
| id | doaj-art-c3ffb23e24c44507ae089440d38cd361 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj-art-c3ffb23e24c44507ae089440d38cd3612025-08-20T03:45:49ZengNature PortfolioScientific Reports2045-23222025-08-0115111410.1038/s41598-025-14626-4Ginkgolide B attenuates hyperlipidemia by restoring sphingolipid homeostasis and activating PPARα and Nrf2 pathwaysYun Liu0Feng Wang1Hengyu Xu2Hongxin Wang3Meili Lu4Lan Cheng5Department of Pharmacy, Liaoning Vocational College of MedicineDepartment of Pharmacy, Liaoning Vocational College of MedicineMedical Mass Spectrometry Technology Innovation Center of Liaoning Province, Shenyang Harmony Health Medical LaboratoryKey Laboratory of Cardiovascular and Cerebrovascular Drug Research of Liaoning Province, Jinzhou Medical UniversityKey Laboratory of Cardiovascular and Cerebrovascular Drug Research of Liaoning Province, Jinzhou Medical UniversitySchool of Pharmacy, Liaoning University of Traditional Chinese MedicineAbstract Although hyperlipidemia is a key factor in cardiovascular disease, there are limited safe and effective therapies for disorders of lipid metabolism. This study investigated the therapeutic potential of Ginkgolide B (GB), a bioactive component of Ginkgo biloba leaves, in ameliorating hyperlipidemia and explored its underlying mechanisms. Utilizing a high-fat diet-induced hyperlipidemic rat model and lipidomics analysis, the study showed that GB significantly decreased serum total cholesterol, triglyceride, and low-density lipoprotein levels. Lipidomics revealed that GB reversed dysregulated sphingolipid metabolism, notably decreasing ceramides levels and increasing sphingomyelins, which are implicated in metabolic inflammation and oxidative stress. Mechanistically, GB activated PPARα, thereby enhancing fatty acid oxidation and upregulating the Nrf2 pathway to mitigate oxidative damage. These dual effects were validated in vitro using HepG2 cells, where GB reduced lipid accumulation and improved antioxidant defenses. Overall, these findings highlight GB as a promising therapeutic agent for hyperlipidemia by restoring sphingolipid homeostasis and targeting the interplay between lipid metabolism and oxidative stress.https://doi.org/10.1038/s41598-025-14626-4Ginkgolide BHyperlipidemiaLipid metabolismCeramideSphingomyelin |
| spellingShingle | Yun Liu Feng Wang Hengyu Xu Hongxin Wang Meili Lu Lan Cheng Ginkgolide B attenuates hyperlipidemia by restoring sphingolipid homeostasis and activating PPARα and Nrf2 pathways Scientific Reports Ginkgolide B Hyperlipidemia Lipid metabolism Ceramide Sphingomyelin |
| title | Ginkgolide B attenuates hyperlipidemia by restoring sphingolipid homeostasis and activating PPARα and Nrf2 pathways |
| title_full | Ginkgolide B attenuates hyperlipidemia by restoring sphingolipid homeostasis and activating PPARα and Nrf2 pathways |
| title_fullStr | Ginkgolide B attenuates hyperlipidemia by restoring sphingolipid homeostasis and activating PPARα and Nrf2 pathways |
| title_full_unstemmed | Ginkgolide B attenuates hyperlipidemia by restoring sphingolipid homeostasis and activating PPARα and Nrf2 pathways |
| title_short | Ginkgolide B attenuates hyperlipidemia by restoring sphingolipid homeostasis and activating PPARα and Nrf2 pathways |
| title_sort | ginkgolide b attenuates hyperlipidemia by restoring sphingolipid homeostasis and activating pparα and nrf2 pathways |
| topic | Ginkgolide B Hyperlipidemia Lipid metabolism Ceramide Sphingomyelin |
| url | https://doi.org/10.1038/s41598-025-14626-4 |
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