The Cholesterol-Lowering Effect of Capsella Bursa-Pastoris Is Mediated via SREBP2 and HNF-1α-Regulated PCSK9 Inhibition in Obese Mice and HepG2 Cells
The objective of the present study was to investigate the mechanism by which capsella bursa-pastoris ethanol extract (CBE), containing 17.5 milligrams of icaritin per kilogram of the extract, and icaritin, mediate hypocholesterolemic activity via the low-density lipoprotein receptor (LDLR) and pro-p...
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MDPI AG
2021-02-01
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| Series: | Foods |
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| Online Access: | https://www.mdpi.com/2304-8158/10/2/408 |
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| author | Jin-Taek Hwang Eunji Choi Hyo-Kyoung Choi Jae-Ho Park Min-Yu Chung |
| author_facet | Jin-Taek Hwang Eunji Choi Hyo-Kyoung Choi Jae-Ho Park Min-Yu Chung |
| author_sort | Jin-Taek Hwang |
| collection | DOAJ |
| description | The objective of the present study was to investigate the mechanism by which capsella bursa-pastoris ethanol extract (CBE), containing 17.5 milligrams of icaritin per kilogram of the extract, and icaritin, mediate hypocholesterolemic activity via the low-density lipoprotein receptor (LDLR) and pro-protein convertase subtilisin/kexin type 9 (PCSK9) in obese mice and HepG2 cells. CBE significantly attenuated serum total and LDL cholesterol levels in obese mice, which was associated with significantly decreased PCSK9 gene expression. HepG2 cells were cultured using delipidated serum (DLPS), and CBE significantly reduced PCSK9 and maintained the LDLR level. CBE co-treatment with rosuvastatin attenuated statin-mediated PCSK9 expression, and further increased LDLR. The icaritin contained in CBE decreased intracellular PCSK9 and LDLR levels by suppressing transcription factors SREBP2 and HNF-1α. Icaritin also significantly suppressed the extracellular PCSK9 level, which likely contributed to post-translational stabilization of LDLR in the HepG2 cells. PCSK9 inhibition by CBE is actively attributed to icaritin, and the use of CBE and icaritin could be an alternative therapeutic approach in the treatment of hypercholesterolemia. |
| first_indexed | 2024-03-09T00:56:32Z |
| format | Article |
| id | doaj.art-5bd0d6ed0b304abd92c0768677aef4a5 |
| institution | Directory Open Access Journal |
| issn | 2304-8158 |
| language | English |
| last_indexed | 2024-03-09T00:56:32Z |
| publishDate | 2021-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Foods |
| spelling | doaj.art-5bd0d6ed0b304abd92c0768677aef4a52023-12-11T16:51:36ZengMDPI AGFoods2304-81582021-02-0110240810.3390/foods10020408The Cholesterol-Lowering Effect of Capsella Bursa-Pastoris Is Mediated via SREBP2 and HNF-1α-Regulated PCSK9 Inhibition in Obese Mice and HepG2 CellsJin-Taek Hwang0Eunji Choi1Hyo-Kyoung Choi2Jae-Ho Park3Min-Yu Chung4Korea Food Research Institute, Wanju-gun, Jeollabuk-do 55365, KoreaDepartment of Food and Nutrition, Sookmyung Women’s University, Seoul 04524, KoreaKorea Food Research Institute, Wanju-gun, Jeollabuk-do 55365, KoreaKorea Food Research Institute, Wanju-gun, Jeollabuk-do 55365, KoreaKorea Food Research Institute, Wanju-gun, Jeollabuk-do 55365, KoreaThe objective of the present study was to investigate the mechanism by which capsella bursa-pastoris ethanol extract (CBE), containing 17.5 milligrams of icaritin per kilogram of the extract, and icaritin, mediate hypocholesterolemic activity via the low-density lipoprotein receptor (LDLR) and pro-protein convertase subtilisin/kexin type 9 (PCSK9) in obese mice and HepG2 cells. CBE significantly attenuated serum total and LDL cholesterol levels in obese mice, which was associated with significantly decreased PCSK9 gene expression. HepG2 cells were cultured using delipidated serum (DLPS), and CBE significantly reduced PCSK9 and maintained the LDLR level. CBE co-treatment with rosuvastatin attenuated statin-mediated PCSK9 expression, and further increased LDLR. The icaritin contained in CBE decreased intracellular PCSK9 and LDLR levels by suppressing transcription factors SREBP2 and HNF-1α. Icaritin also significantly suppressed the extracellular PCSK9 level, which likely contributed to post-translational stabilization of LDLR in the HepG2 cells. PCSK9 inhibition by CBE is actively attributed to icaritin, and the use of CBE and icaritin could be an alternative therapeutic approach in the treatment of hypercholesterolemia.https://www.mdpi.com/2304-8158/10/2/408capsella bursa-pastorisPCSK9LDL receptorSREBP2statinsicaritin |
| spellingShingle | Jin-Taek Hwang Eunji Choi Hyo-Kyoung Choi Jae-Ho Park Min-Yu Chung The Cholesterol-Lowering Effect of Capsella Bursa-Pastoris Is Mediated via SREBP2 and HNF-1α-Regulated PCSK9 Inhibition in Obese Mice and HepG2 Cells Foods capsella bursa-pastoris PCSK9 LDL receptor SREBP2 statins icaritin |
| title | The Cholesterol-Lowering Effect of Capsella Bursa-Pastoris Is Mediated via SREBP2 and HNF-1α-Regulated PCSK9 Inhibition in Obese Mice and HepG2 Cells |
| title_full | The Cholesterol-Lowering Effect of Capsella Bursa-Pastoris Is Mediated via SREBP2 and HNF-1α-Regulated PCSK9 Inhibition in Obese Mice and HepG2 Cells |
| title_fullStr | The Cholesterol-Lowering Effect of Capsella Bursa-Pastoris Is Mediated via SREBP2 and HNF-1α-Regulated PCSK9 Inhibition in Obese Mice and HepG2 Cells |
| title_full_unstemmed | The Cholesterol-Lowering Effect of Capsella Bursa-Pastoris Is Mediated via SREBP2 and HNF-1α-Regulated PCSK9 Inhibition in Obese Mice and HepG2 Cells |
| title_short | The Cholesterol-Lowering Effect of Capsella Bursa-Pastoris Is Mediated via SREBP2 and HNF-1α-Regulated PCSK9 Inhibition in Obese Mice and HepG2 Cells |
| title_sort | cholesterol lowering effect of capsella bursa pastoris is mediated via srebp2 and hnf 1α regulated pcsk9 inhibition in obese mice and hepg2 cells |
| topic | capsella bursa-pastoris PCSK9 LDL receptor SREBP2 statins icaritin |
| url | https://www.mdpi.com/2304-8158/10/2/408 |
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