PMID- 34680102 OWN - NLM STAT- MEDLINE DCOM- 20220112 LR - 20231213 IS - 2218-273X (Electronic) IS - 2218-273X (Linking) VI - 11 IP - 10 DP - 2021 Oct 6 TI - Rosmarinic Acid Exhibits a Lipid-Lowering Effect by Modulating the Expression of Reverse Cholesterol Transporters and Lipid Metabolism in High-Fat Diet-Fed Mice. LID - 10.3390/biom11101470 [doi] LID - 1470 AB - Hyperlipidemia is a potent risk factor for the development of cardiovascular diseases. The reverse cholesterol transport (RCT) process has been shown to alleviate hyperlipidemia and protect against cardiovascular diseases. Recently, rosmarinic acid was reported to exhibit lipid-lowering effects. However, the underlying mechanism is still unclear. This study aims to investigate whether rosmarinic acid lowers lipids by modulating the RCT process in high-fat diet (HFD)-induced hyperlipidemic C57BL/6J mice. Our results indicated that rosmarinic acid treatment significantly decreased body weight, blood glucose, and plasma total cholesterol and triglyceride levels in HFD-fed mice. Rosmarinic acid increased the expression levels of cholesterol uptake-associated receptors in liver tissues, including scavenger receptor B type 1 (SR-B1) and low-density lipoprotein receptor (LDL-R). Furthermore, rosmarinic acid treatment notably increased the expression of cholesterol excretion molecules, ATP-binding cassette G5 (ABCG5) and G8 (ABCG8) transporters, and cholesterol 7 alpha-hydroxylase A1 (CYP7A1) as well as markedly reduced cholesterol and triglyceride levels in liver tissues. In addition, rosmarinic acid facilitated fatty acid oxidation through AMP-activated protein kinase (AMPK)-mediated carnitine palmitoyltransferase 1A (CPT1A) induction. In conclusion, rosmarinic acid exhibited a lipid-lowering effect by modulating the expression of RCT-related proteins and lipid metabolism-associated molecules, confirming its potential for the prevention or treatment of hyperlipidemia-derived diseases. FAU - Nyandwi, Jean Baptiste AU - Nyandwi JB AUID- ORCID: 0000-0003-2265-3187 AD - Department of Pharmacology, Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju 52727, Korea. AD - Department of Convergence Medical Science (BK21 Plus), Gyeongsang National University, Jinju 52727, Korea. AD - Department of Pharmacy, School of Medicine and Pharmacy, College of Medicine and Health Sciences, University of Rwanda, Kigali 4285, Rwanda. FAU - Ko, Young Shin AU - Ko YS AD - Department of Pharmacology, Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju 52727, Korea. FAU - Jin, Hana AU - Jin H AD - Department of Pharmacology, Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju 52727, Korea. FAU - Yun, Seung Pil AU - Yun SP AD - Department of Pharmacology, Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju 52727, Korea. AD - Department of Convergence Medical Science (BK21 Plus), Gyeongsang National University, Jinju 52727, Korea. FAU - Park, Sang Won AU - Park SW AUID- ORCID: 0000-0002-6149-5284 AD - Department of Pharmacology, Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju 52727, Korea. AD - Department of Convergence Medical Science (BK21 Plus), Gyeongsang National University, Jinju 52727, Korea. FAU - Kim, Hye Jung AU - Kim HJ AUID- ORCID: 0000-0002-7067-6810 AD - Department of Pharmacology, Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju 52727, Korea. AD - Department of Convergence Medical Science (BK21 Plus), Gyeongsang National University, Jinju 52727, Korea. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20211006 PL - Switzerland TA - Biomolecules JT - Biomolecules JID - 101596414 RN - 0 (ABCG5 protein, mouse) RN - 0 (ABCG8 protein, mouse) RN - 0 (ATP Binding Cassette Transporter, Subfamily G, Member 5) RN - 0 (ATP Binding Cassette Transporter, Subfamily G, Member 8) RN - 0 (Cinnamates) RN - 0 (Depsides) RN - 0 (Lipoproteins) RN - 0 (Receptors, LDL) RN - 0 (Scarb1 protein, mouse) RN - 0 (Scavenger Receptors, Class B) RN - 97C5T2UQ7J (Cholesterol) RN - EC 1.14.14.23 (Cholesterol 7-alpha-Hydroxylase) RN - EC 1.14.14.23 (Cyp7a1 protein, mouse) RN - EC 2.3.1.21 (CPT1B protein, mouse) RN - EC 2.3.1.21 (Carnitine O-Palmitoyltransferase) RN - EC 2.7.11.3 (AMP-Activated Protein Kinase Kinases) SB - IM MH - AMP-Activated Protein Kinase Kinases/genetics MH - ATP Binding Cassette Transporter, Subfamily G, Member 5/genetics MH - ATP Binding Cassette Transporter, Subfamily G, Member 8/genetics MH - Animals MH - Cardiovascular Diseases/*drug therapy/metabolism/pathology/prevention & control MH - Carnitine O-Palmitoyltransferase/genetics MH - Cholesterol/genetics/metabolism MH - Cholesterol 7-alpha-Hydroxylase/genetics MH - Cinnamates/*pharmacology MH - Depsides/*pharmacology MH - Diet, High-Fat/adverse effects MH - Disease Models, Animal MH - Gene Expression Regulation/drug effects MH - Humans MH - Hyperlipidemias/*drug therapy/metabolism/pathology/prevention & control MH - Lipid Metabolism/drug effects MH - Lipoproteins/genetics MH - Liver/drug effects/metabolism MH - Male MH - Mice MH - Receptors, LDL/*genetics MH - Scavenger Receptors, Class B/*genetics MH - Rosmarinic Acid PMC - PMC8533102 OTO - NOTNLM OT - ABC transporters OT - AMPK OT - RCT OT - hyperlipidemia OT - rosmarinic acid COIS- The authors declare no conflict of interest. EDAT- 2021/10/24 06:00 MHDA- 2022/01/13 06:00 PMCR- 2021/10/06 CRDT- 2021/10/23 01:03 PHST- 2021/09/08 00:00 [received] PHST- 2021/09/29 00:00 [revised] PHST- 2021/10/01 00:00 [accepted] PHST- 2021/10/23 01:03 [entrez] PHST- 2021/10/24 06:00 [pubmed] PHST- 2022/01/13 06:00 [medline] PHST- 2021/10/06 00:00 [pmc-release] AID - biom11101470 [pii] AID - biomolecules-11-01470 [pii] AID - 10.3390/biom11101470 [doi] PST - epublish SO - Biomolecules. 2021 Oct 6;11(10):1470. doi: 10.3390/biom11101470.