Purple Perilla Frutescens Extracts Containing α-asarone Inhibit Inflammatory Atheroma Formation and Promote Hepatic HDL Cholesterol Uptake in Dyslipidemic ApoE-deficient Mice

Overview

Journal Nutr Res Pract

Specialty Nutritional Sciences

Date 2023 Dec 6

PMID 38053825

Authors

Sin-Hye Park

Young Eun Sim

Min-Kyung Kang

Dong Yeon Kim

Il-Jun Kang

Soon Sung Lim

Young-Hee Kang

Affiliations

Soon will be listed here.

Abstract

Background/objectives: Dyslipidemia causes metabolic disorders such as atherosclerosis and fatty liver syndrome due to abnormally high blood lipids. Purple perilla frutescens extract (PPE) possesses various bioactive compounds such as α-asarone, chlorogenic acid and rosmarinic acid. This study examined whether PPE and α-asarone improved dyslipidemia-associated inflammation and inhibited atheroma formation in apolipoprotein E (apoE)-deficient mice, an experimental animal model of atherosclerosis.

Materials/methods: ApoE-deficient mice were fed on high cholesterol-diet (Paigen's diet) and orally administrated with 10-20 mg/kg PPE and α-asarone for 10 wk.

Results: The Paigen's diet reduced body weight gain in apoE-deficient mice, which was not restored by PPE or α-asarone. PPE or α-asarone improved the plasma lipid profiles in Paigen's diet-fed apoE-deficient mice, and despite a small increase in high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein (LDL)-cholesterol, and very LDL were significantly reduced. Paigen's diet-induced systemic inflammation was reduced in PPE or α-asarone-treated apoE-deficient mice. Supplying PPE or α-asarone to mice lacking apoE suppressed aorta atherogenesis induced by atherogenic diet. PPE or α-asarone diminished aorta accumulation of CD68- and/or F4/80-positive macrophages induced by atherogenic diet in apoE-deficient mice. Treatment of apoE-deficient mice with PPE and α-asarone resulted in a significant decrease in plasma cholesteryl ester transfer protein level and an increase in lecithin:cholesterol acyltransferase reduced by supply of Paigen's diet. Supplementation of PPE and α-asarone enhanced the transcription of hepatic apoA1 and SR-B1 reduced by Paigen's diet in apoE-deficient mice.

Conclusions: α-Asarone in PPE inhibited inflammation-associated atheroma formation and promoted hepatic HDL-C trafficking in dyslipidemic mice.

Citing Articles

Dietary ellagic acid blocks inflammation-associated atherosclerotic plaque formation in cholesterol-fed apoE-deficient mice.

Park S, Kang M, Kim D, Lim S, Kang Y Nutr Res Pract. 2024; 18(5):617-632.

PMID: 39398881 PMC: 11464280. DOI: 10.4162/nrp.2024.18.5.617.

References

Mahley R . Apolipoprotein E: from cardiovascular disease to neurodegenerative disorders. J Mol Med (Berl). 2016; 94(7):739-46. PMC: 4921111. DOI: 10.1007/s00109-016-1427-y. View

Kones R, Rumana U . Current Treatment of Dyslipidemia: Evolving Roles of Non-Statin and Newer Drugs. Drugs. 2015; 75(11):1201-28. DOI: 10.1007/s40265-015-0429-3. View

Peng Y, Xu J, Zeng Y, Chen L, Le Xu X . Polydatin attenuates atherosclerosis in apolipoprotein E-deficient mice: Role of reverse cholesterol transport. Phytomedicine. 2019; 62:152935. DOI: 10.1016/j.phymed.2019.152935. View

Phillips M . Apolipoprotein E isoforms and lipoprotein metabolism. IUBMB Life. 2014; 66(9):616-23. DOI: 10.1002/iub.1314. View

Nakashima Y, Plump A, Raines E, Breslow J, Ross R . ApoE-deficient mice develop lesions of all phases of atherosclerosis throughout the arterial tree. Arterioscler Thromb. 1994; 14(1):133-40. DOI: 10.1161/01.atv.14.1.133. View

Olszanecki R, Jawien J, Gajda M, Mateuszuk L, Gebska A, Korabiowska M . Effect of curcumin on atherosclerosis in apoE/LDLR-double knockout mice. J Physiol Pharmacol. 2006; 56(4):627-35. View

Rochlani Y, Pothineni N, Kovelamudi S, Mehta J . Metabolic syndrome: pathophysiology, management, and modulation by natural compounds. Ther Adv Cardiovasc Dis. 2017; 11(8):215-225. PMC: 5933580. DOI: 10.1177/1753944717711379. View

Moghadasian M, McManus B, Nguyen L, SHEFER S, Nadji M, Godin D . Pathophysiology of apolipoprotein E deficiency in mice: relevance to apo E-related disorders in humans. FASEB J. 2001; 15(14):2623-30. DOI: 10.1096/fj.01-0463com. View

Xu M, Lv C, Wang H, Lu Q, Ye M, Zhu X . Peanut skin extract ameliorates high-fat diet-induced atherosclerosis by regulating lipid metabolism, inflammation reaction and gut microbiota in ApoE mice. Food Res Int. 2022; 154:111014. DOI: 10.1016/j.foodres.2022.111014. View

10.

Park S, Shin D, Lim S, Lee J, Kang Y . Purple perilla extracts allay ER stress in lipid-laden macrophages. PLoS One. 2014; 9(10):e110581. PMC: 4198214. DOI: 10.1371/journal.pone.0110581. View

11.

Millar C, Duclos Q, Blesso C . Effects of Dietary Flavonoids on Reverse Cholesterol Transport, HDL Metabolism, and HDL Function. Adv Nutr. 2017; 8(2):226-239. PMC: 5347106. DOI: 10.3945/an.116.014050. View

12.

Lo Sasso G, Schlage W, Boue S, Veljkovic E, Peitsch M, Hoeng J . The Apoe(-/-) mouse model: a suitable model to study cardiovascular and respiratory diseases in the context of cigarette smoke exposure and harm reduction. J Transl Med. 2016; 14(1):146. PMC: 4875735. DOI: 10.1186/s12967-016-0901-1. View

13.

Farrell N, Norris G, Lee S, Chun O, Blesso C . Anthocyanin-rich black elderberry extract improves markers of HDL function and reduces aortic cholesterol in hyperlipidemic mice. Food Funct. 2015; 6(4):1278-87. DOI: 10.1039/c4fo01036a. View

14.

Huang W, Zeng Z, Lang Y, Xiang X, Qi G, Lu G . Seed Oil Alleviates Experimental Atherosclerosis by Ameliorating Vascular Inflammation in Apolipoprotein-E-Deficient Mice. J Agric Food Chem. 2021; 69(32):9102-9110. DOI: 10.1021/acs.jafc.0c07251. View

15.

Chowaniec Z, Skoczynska A . Plasma lipid transfer proteins: The role of PLTP and CETP in atherogenesis. Adv Clin Exp Med. 2018; 27(3):429-436. DOI: 10.17219/acem/67968. View

16.

Wu C, Luan H, Zhang X, Wang S, Zhang X, Sun X . Chlorogenic acid protects against atherosclerosis in ApoE-/- mice and promotes cholesterol efflux from RAW264.7 macrophages. PLoS One. 2014; 9(9):e95452. PMC: 4154672. DOI: 10.1371/journal.pone.0095452. View

17.

Rodriguez-Paez L, Juarez-Sanchez M, Antunez-Solis J, Baeza I, Wong C . Alpha-asarone inhibits HMG-CoA reductase, lowers serum LDL-cholesterol levels and reduces biliary CSI in hypercholesterolemic rats. Phytomedicine. 2003; 10(5):397-404. DOI: 10.1078/0944-7113-00274. View

18.

Mahley R, Rall Jr S . Apolipoprotein E: far more than a lipid transport protein. Annu Rev Genomics Hum Genet. 2001; 1:507-37. DOI: 10.1146/annurev.genom.1.1.507. View

19.

Liu S, Jin X, Shang Y, Wang L, Du K, Chen S . A comprehensive review of the botany, ethnopharmacology, phytochemistry, pharmacology, toxicity and quality control of Perillae Fructus. J Ethnopharmacol. 2022; 304:116022. DOI: 10.1016/j.jep.2022.116022. View

20.

De Giorgi M, Li A, Hurley A, Barzi M, Doerfler A, Cherayil N . Targeting the locus for liver-directed gene therapy. Mol Ther Methods Clin Dev. 2021; 21:656-669. PMC: 8166646. DOI: 10.1016/j.omtm.2021.04.011. View