Lipid regulation of protocatechualdehyde and hydroxysafflor yellow A via AMPK/SREBP2/PCSK9/LDLR signaling pathway in hyperlipidemic zebrafish
Bingying Lin,
Haofang Wan,
Jiehong Yang,
Li Yu,
Huifen Zhou,
Haitong Wan
Affiliations
Bingying Lin
School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
Haofang Wan
Academy of Chinese Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
Jiehong Yang
School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
Li Yu
School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, China; Institute of Cardio-Cerebrovascular Diseases, Zhejiang Chinese Medical University, Hangzhou, China; Key Laboratory of TCM Encephalopathy of Zhejiang Province (grant no. 2020E10012), Hangzhou, China
Huifen Zhou
School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, China; Institute of Cardio-Cerebrovascular Diseases, Zhejiang Chinese Medical University, Hangzhou, China; Key Laboratory of TCM Encephalopathy of Zhejiang Province (grant no. 2020E10012), Hangzhou, China; Corresponding author. Zhejiang Chinese Medical University, 548 Binwen Road, Hangzhou, 310053, China.
Haitong Wan
School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, China; Institute of Cardio-Cerebrovascular Diseases, Zhejiang Chinese Medical University, Hangzhou, China; First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China; Key Laboratory of TCM Encephalopathy of Zhejiang Province (grant no. 2020E10012), Hangzhou, China; Corresponding author. Zhejiang Chinese Medical University, 548 Binwen Road, Hangzhou, 310053, China.
The consumption of a high-cholesterol diet is known to cause hyperlipidemia, which is one of the main risk factors for cardiovascular disease. Protocatechualdehyde (PCA) and hydroxysafflor yellow A (HSYA) are the active components of Salvia miltiorrhiza and safflower, respectively. However, their exact mechanism is still unclear. The aim of this study is to investigate its effects on lipid deposition and liver damage in hyperlipidemic zebrafish and its mechanism of anti-hyperlipidemia. The results showed that the use of PCA and HSYA alone and in combination can improve lipid deposition, slow behavior, abnormal blood flow and liver tissue damage, and the combined use is more effective. Further RT-qPCR results showed that PCA + HSYA can regulate the mRNA levels of PPAR-γ, SREBP2, SREBP1, HMGCR, PCSK9, mTOR, C/EBPα, LDLR, AMPK, HNF-1α and FoxO3a. The PCA + HSYA significantly improves lipid deposition and abnormal liver function in hyperlipidemic zebrafish larvae, which may be related to the AMPK/SREBP2/PCSK9/LDLR signaling pathway.
