Dihydromyricetin promotes LDL metabolism in HepG2 cells through the PCSK9/LDLR pathway

ABSTRACTLow-density lipoprotein receptor (LDLR) and proprotein convertase subtilisin/kexin type 9 (PCSK9) play a pivotal role by regulating plasma low-density lipoprotein cholesterol (LDL-c) levels. Dihydromyricetin (DMY), the most abundant natural flavonoid in rattan tea, has proven anti-atherogeni...

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Main Authors: Li-Tian Wang, Dan-Dan Hu, Hua-Rong Liu, Huai-Liu Yin, Rui Mu, Yu-Hang Yang, Run-Yu Zhao, Jun Sheng, Ye-Wei Huang, Xuan-Jun Wang
Format: Article
Language:English
Published: Taylor & Francis Group 2023-12-01
Series:CyTA - Journal of Food
Subjects:
Online Access:https://www.tandfonline.com/doi/10.1080/19476337.2023.2252044
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author Li-Tian Wang
Dan-Dan Hu
Hua-Rong Liu
Huai-Liu Yin
Rui Mu
Yu-Hang Yang
Run-Yu Zhao
Jun Sheng
Ye-Wei Huang
Xuan-Jun Wang
author_facet Li-Tian Wang
Dan-Dan Hu
Hua-Rong Liu
Huai-Liu Yin
Rui Mu
Yu-Hang Yang
Run-Yu Zhao
Jun Sheng
Ye-Wei Huang
Xuan-Jun Wang
author_sort Li-Tian Wang
collection DOAJ
description ABSTRACTLow-density lipoprotein receptor (LDLR) and proprotein convertase subtilisin/kexin type 9 (PCSK9) play a pivotal role by regulating plasma low-density lipoprotein cholesterol (LDL-c) levels. Dihydromyricetin (DMY), the most abundant natural flavonoid in rattan tea, has proven anti-atherogenic effects, but the underlying molecular mechanisms remain poorly understood. Therefore, we studied the effects of DMY on LDLR and PCSK9. The results showed DMY promoted LDLR protein and mRNA expression and increased LDL uptake in HepG2 cells. DMY inhibited intracellular PCSK9 protein and mRNA expression. And it also significantly reduced PCSK9 levels in the cell culture medium. Furthermore, DMY inhibited the expression of PCSK9 through the liver nuclear transcription factor 1 A (HNF1A) and increased the protein expression of LDLR. Taken together, our results support the idea that DMY regulates LDL-c metabolism through PCSK9/LDLR signaling. This study reveals the potential mechanism of DMY’s anti-atherogenic effect and provides a theoretical basis for dietary DMY supplementation.
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spelling doaj.art-3fe7cb1779a54e69b25a333a172407762023-12-13T14:31:46ZengTaylor & Francis GroupCyTA - Journal of Food1947-63371947-63452023-12-0121155456010.1080/19476337.2023.2252044Dihydromyricetin promotes LDL metabolism in HepG2 cells through the PCSK9/LDLR pathwayLi-Tian Wang0Dan-Dan Hu1Hua-Rong Liu2Huai-Liu Yin3Rui Mu4Yu-Hang Yang5Run-Yu Zhao6Jun Sheng7Ye-Wei Huang8Xuan-Jun Wang9Key Laboratory of Pu-er Tea Science, Ministry of Education, Yunnan Agricultural University, Kunming, ChinaKey Laboratory of Pu-er Tea Science, Ministry of Education, Yunnan Agricultural University, Kunming, ChinaKey Laboratory of Pu-er Tea Science, Ministry of Education, Yunnan Agricultural University, Kunming, ChinaKey Laboratory of Pu-er Tea Science, Ministry of Education, Yunnan Agricultural University, Kunming, ChinaCollege of Science, Yunnan Agricultural University, Kunming, ChinaCollege of Science, Yunnan Agricultural University, Kunming, ChinaCollege of Science, Yunnan Agricultural University, Kunming, ChinaKey Laboratory of Pu-er Tea Science, Ministry of Education, Yunnan Agricultural University, Kunming, ChinaKey Laboratory of Pu-er Tea Science, Ministry of Education, Yunnan Agricultural University, Kunming, ChinaKey Laboratory of Pu-er Tea Science, Ministry of Education, Yunnan Agricultural University, Kunming, ChinaABSTRACTLow-density lipoprotein receptor (LDLR) and proprotein convertase subtilisin/kexin type 9 (PCSK9) play a pivotal role by regulating plasma low-density lipoprotein cholesterol (LDL-c) levels. Dihydromyricetin (DMY), the most abundant natural flavonoid in rattan tea, has proven anti-atherogenic effects, but the underlying molecular mechanisms remain poorly understood. Therefore, we studied the effects of DMY on LDLR and PCSK9. The results showed DMY promoted LDLR protein and mRNA expression and increased LDL uptake in HepG2 cells. DMY inhibited intracellular PCSK9 protein and mRNA expression. And it also significantly reduced PCSK9 levels in the cell culture medium. Furthermore, DMY inhibited the expression of PCSK9 through the liver nuclear transcription factor 1 A (HNF1A) and increased the protein expression of LDLR. Taken together, our results support the idea that DMY regulates LDL-c metabolism through PCSK9/LDLR signaling. This study reveals the potential mechanism of DMY’s anti-atherogenic effect and provides a theoretical basis for dietary DMY supplementation.https://www.tandfonline.com/doi/10.1080/19476337.2023.2252044Cholesterol metabolismASCVDHNF1ALDLRPCSK9
spellingShingle Li-Tian Wang
Dan-Dan Hu
Hua-Rong Liu
Huai-Liu Yin
Rui Mu
Yu-Hang Yang
Run-Yu Zhao
Jun Sheng
Ye-Wei Huang
Xuan-Jun Wang
Dihydromyricetin promotes LDL metabolism in HepG2 cells through the PCSK9/LDLR pathway
CyTA - Journal of Food
Cholesterol metabolism
ASCVD
HNF1A
LDLR
PCSK9
title Dihydromyricetin promotes LDL metabolism in HepG2 cells through the PCSK9/LDLR pathway
title_full Dihydromyricetin promotes LDL metabolism in HepG2 cells through the PCSK9/LDLR pathway
title_fullStr Dihydromyricetin promotes LDL metabolism in HepG2 cells through the PCSK9/LDLR pathway
title_full_unstemmed Dihydromyricetin promotes LDL metabolism in HepG2 cells through the PCSK9/LDLR pathway
title_short Dihydromyricetin promotes LDL metabolism in HepG2 cells through the PCSK9/LDLR pathway
title_sort dihydromyricetin promotes ldl metabolism in hepg2 cells through the pcsk9 ldlr pathway
topic Cholesterol metabolism
ASCVD
HNF1A
LDLR
PCSK9
url https://www.tandfonline.com/doi/10.1080/19476337.2023.2252044
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