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To investigate the mechanism of Hydroxysafflor yellow A in the treatment of hyperlipidemia in LDLR-/- mice based on lipid metabolomics
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DOI   10.11656/j.issn.1673-9043.2024.01.01
Key Words   Hydroxysafflor yellow A;hyperlipidemia;lipidomics;metabolism of lipid
Author NameAffiliationE-mail
TANG Huajing Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China  
LUO Yage Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China  
YANG Lei Youcare Pharmaceutical Group Co., Ltd., Beijing 100176, China  
XU Baoxin Youcare Pharmaceutical Group Co., Ltd., Beijing 100176, China  
XU Jingya Youcare Pharmaceutical Group Co., Ltd., Beijing 100176, China  
MIAO Lin Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China  
CHAI Lijuan Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China  
ZHANG Han Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China  
WANG Yi Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China  
MAO Haoping Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China maohaoping@tjutcm.edu.cn 
Abstract
    [Objective] To investigate the effect and mechanism of Hydroxysafflor yellow A(HSYA) on lipid metabolism in LDLR-/- mice with hyperlipidemia induced by high-fat diet based on lipid metabolomics. [Methods] Twenty-eight male LDLR-/- mice were divided into control group and high-fat diet group. The control group was fed with normal diet, and the high-fat group was fed with high-fat diet. After 6 weeks, according to the content of LDL-C, the mice were divided into four groups[model group, simvastatin group, low dose HSYA(3.8 mg/kg) and high dose HSYA(7.6 mg/kg)]. The drug was administered for 11 weeks, and high-fat diet was given simultaneously during the drug administration. The content of alanine aminotransferase(ALT), aspartate aminotransferase(AST), triglyceride(TG), total cholesterol(TC), and low-density lipoprotein cholesterol(LDL-C) in serum of mice were detected by automatic biochemical instrument, the pathological morphology of liver histology was observed by hematoxylin-eosin staining, and the fat deposition of liver tissues of mice was observed by oil red O staining, and lipids in the serum of LDLR-/- mice were measured by targeted lipidomic technology. [Results] Compared with the control group, the serum content of LDL-C, TC, TG, AST and ALT in the model group were increased(P<0.05). The liver tissue showed infiltration of lipid droplets of different sizes, disorderly arrangement of hepatocytes, and a large number of lipid deposits. Compared with the model group, the serum content of LDL-C, TC, TG, AST and ALT in the HSYA group were decreased(P<0.05), liver steatosis, lipid deposition and other pathological conditions were improved. The results of lipid profiling showed that there were 14 different lipid molecules(VIP>1, P<0.05). Compared with the model group, 17 lipid molecules in the HSYA group showed the opposite trend and had differences, Respectively PE(18:0/18:1), PE(18:0/18:2), PE(18:0/20:3), PE(18:0/20:4), PE(O-18:0/18:1), PE(O-18:0/20:4), LPE(18:1), LPE(20:4), FFA(22:4), PI(18:0/18:2), PI(16:0/18:1), PI(18:1/18:1), LPI(18:0), PG(18:1/16:1), PG(18:1/18:1), PG(18:1/18:2), PA(18:1/18:1)(VIP>1, P<0.05). [Conclusion] Using lipidomics technology, this study found that HSYA could play a role in the treatment of hyperlipidemia by regulating lipid metabolism in the serum of hyperlipidemia LDLR-/- mice, and provided a new reference for its clinical application.

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