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Current Neurovascular Research

Editor-in-Chief

ISSN (Print): 1567-2026
ISSN (Online): 1875-5739

Research Article

Extract of Gualou-Xiebai Herb Pair Improves Lipid Metabolism Disorders by Enhancing the Reverse Cholesterol Transport in Atherosclerosis Mice

Author(s): Yarong Liu, Tian Wang, Lidan Ding, Zhenglong Li, Yexiang Zhang, Min Dai and Hongfei Wu*

Volume 21, Issue 2, 2024

Published on: 15 April, 2024

Page: [214 - 227] Pages: 14

DOI: 10.2174/0115672026308438240405055719

Price: $65

Abstract

Background: Gualou is derived from the fruit of Trichosanthes kirilowii Maxim, while Xiebai from the bulbs of Allium macrostemon Bunge. Gualou and Xiebai herb pair (2:1) is widely used in clinical practice to treat atherosclerotic cardiovascular diseases. However, the mechanism underlying its potential activity on atherosclerosis (AS) has not been fully elucidated.

Methods: The extract of Gualou-Xiebai herb pair (GXE) was prepared from Gualou (80 g) and Xiebai (40 g) by continuous refluxing with 50% ethanol for 2 h at 80°C. In vivo, ApoE-/- mice were fed a high-fat diet (HFD) for 10 weeks to induce an AS model, and then the mice were treated with GXE (3, 6, 12 g/kg) or atorvastatin (10 mg/kg) via oral gavage. Besides, RAW264.7 macrophages were stimulated by ox-LDL to establish a foam cell model in vitro.

Results: GXE suppressed plaque formation, regulated plasma lipids, and promoted liver lipid clearance in AS mice. In addition, 0.5, 1, and 2 mg/mL GXE significantly reduced the TC and FC levels in ox-LDL (50 μg/mL)-stimulated foam cells. GXE increased cholesterol efflux from the foam cells to ApoA-1 and HDL, and enhanced the protein expressions of ABCA1, ABCG1, and SR-BI, which were reversed by the PPARγ inhibitor. Meanwhile, GXE increased the LCAT levels, decreased the lipid levels and increased the TBA levels in the liver of AS mice. Molecular docking indicated that some compounds in GXE showed favorable binding energy with PPARγ, LCAT and CYP7A1 proteins, especially apigenin-7-O-β-D-glucoside and quercetin.

Conclusion: In summary, our results suggested that GXE improved lipid metabolism disorders by enhancing RCT, providing a scientific basis for the clinical use of GXE in AS treatment.

« Previous
[1]
Perrotta I. Atherosclerosis: From molecular biology to therapeutic perspective 3.0. Int J Mol Sci 2023; 24(8): 6897.
[http://dx.doi.org/10.3390/ijms24086897] [PMID: 37108058]
[2]
Kolaszyńska O, Lorkowski J. Symmetry and asymmetry in atherosclerosis. Int J Occup Med Environ Health 2023; 36(6): 693-703.
[http://dx.doi.org/10.13075/ijomeh.1896.02171] [PMID: 37791506]
[3]
Libby P, Buring JE, Badimon L, et al. Atherosclerosis. Nat Rev Dis Primers 2019; 5(1): 56.
[http://dx.doi.org/10.1038/s41572-019-0106-z] [PMID: 31420554]
[4]
Arvanitis M, Lowenstein CJ. Dyslipidemia. Ann Intern Med 2023; 176(6): ITC81-96.
[http://dx.doi.org/10.7326/AITC202306200] [PMID: 37307585]
[5]
Delialis D, Georgiopoulos G, Aivalioti E, et al. Remnant cholesterol and atherosclerotic disease in high cardiovascular risk patients. Beyond LDL cholesterol and hypolipidemic treatment. Hellenic J Cardiol 2022; 66: 26-31.
[http://dx.doi.org/10.1016/j.hjc.2022.05.011] [PMID: 35667617]
[6]
Wadström BN, Pedersen KM, Wulff AB, Nordestgaard BG. Elevated remnant cholesterol, plasma triglycerides, and cardiovascular and non-cardiovascular mortality. Eur Heart J 2023; 44(16): 1432-45.
[http://dx.doi.org/10.1093/eurheartj/ehac822] [PMID: 36631967]
[7]
Gasbarrino K, Hafiane A, Gianopoulos I, Zheng H, Mantzoros CS, Daskalopoulou SS. Relationship between circulating adipokines and cholesterol efflux in subjects with severe carotid atherosclerosis. Metabolism 2023; 140: 155381.
[http://dx.doi.org/10.1016/j.metabol.2022.155381] [PMID: 36566801]
[8]
Rohatgi A. Reverse cholesterol transport and atherosclerosis. Arterioscler Thromb Vasc Biol 2019; 39(1): 2-4.
[http://dx.doi.org/10.1161/ATVBAHA.118.311978] [PMID: 30586333]
[9]
Xie J, Peng L. wang T, et al. QiShenYiQi pill inhibits atherosclerosis by promoting reverse cholesterol transport PPARγ-LXRα/β-ABCA1 pathway. J Ethnopharmacol 2023; 315: 116684.
[http://dx.doi.org/10.1016/j.jep.2023.116684]
[10]
Pownall HJ, Rosales C, Gillard BK, Gotto AM Jr. High-density lipoproteins, reverse cholesterol transport and atherogenesis. Nat Rev Cardiol 2021; 18(10): 712-23.
[http://dx.doi.org/10.1038/s41569-021-00538-z] [PMID: 33833449]
[11]
Peng Y, Xu J, Zeng Y, Chen L, Xu XL. Polydatin attenuates atherosclerosis in apolipoprotein E-deficient mice: Role of reverse cholesterol transport. Phytomedicine 2019; 62: 152935.
[http://dx.doi.org/10.1016/j.phymed.2019.152935] [PMID: 31085374]
[12]
Flores R, Jin X, Chang J, et al. LCAT, ApoD, and ApoA1 expression and review of cholesterol deposition in the cornea. Biomolecules 2019; 9(12): 785.
[http://dx.doi.org/10.3390/biom9120785] [PMID: 31779197]
[13]
Liu Y, Zhong H, Xu P, et al. Deciphering the combination mechanisms of Gualou–Xiebai herb pair against atherosclerosis by network pharmacology and HPLC-Q-TOF-MS technology. Front Pharmacol 2022; 13: 941400.
[http://dx.doi.org/10.3389/fphar.2022.941400] [PMID: 36120369]
[14]
Zhang WY, Yu Y, Yan LL, et al. Discovery of cardio-protective constituents of gualou xiebai decoction, a classical traditional Chinese medicinal formula. Phytomedicine 2019; 54: 318-27.
[http://dx.doi.org/10.1016/j.phymed.2018.04.047] [PMID: 30060904]
[15]
Wu R, Liu X, Wang J, Zhou XZ. Study on law using Chinese drug of famous old docter of traditional Chinese medicine to coronary heart disease based on association rules. Zhongguo Zhongyao Zazhi 2007; 32(17): 1786-8.
[PMID: 17993003]
[16]
Lu X, Xu H, Zhao T, Li G. Study of serum metabonomics and formula-pattern correspondence in coronary heart disease patients diagnosed as phlegm or blood stasis pattern based on ultra performance liquid chromatography mass spectrometry. Chin J Integr Med 2018; 24(12): 905-11.
[http://dx.doi.org/10.1007/s11655-018-2564-7] [PMID: 29948595]
[17]
Ding L, Xu P, Bao Y, Huang J, Wu H. Effects of trichosanthis fructus-allii macrostemonis bulbus on the activation of NLRP3 inflammasomes in ApoE-/- mice at different stages of atherosclerosis. Chinese Journal of Atherosclerosis 2022; 30(1): 9.
[18]
Luo M, Fan R, Wang X, et al. Gualou xiebai banxia decoction ameliorates poloxamer 407-induced hyperlipidemia. Biosci Rep 2021; 41(6): BSR20204216.
[http://dx.doi.org/10.1042/BSR20204216] [PMID: 34036306]
[19]
Yan LL, Zhang WY, Wei XH, et al. Gualou xiebai decoction, a traditional chinese medicine, prevents cardiac reperfusion injury of hyperlipidemia rat via energy modulation. Front Physiol 2018; 9: 296.
[http://dx.doi.org/10.3389/fphys.2018.00296] [PMID: 29674972]
[20]
Xu PB, Ding LD, Qiu JW, et al. Study on effect of “Trichosanthis Fructus-Allii Macrostemonis Bulbus” on atherosclerosis in ApoE~(-/-) mice based on liver metabonomics. Zhongguo Zhongyao Zazhi 2021; 46(20): 5320-9.
[PMID: 34738436]
[21]
Zhang K, Song W, Li D, Jin X. Apigenin in the regulation of cholesterol metabolism and protection of blood vessels. Exp Ther Med 2017; 13(5): 1719-24.
[http://dx.doi.org/10.3892/etm.2017.4165] [PMID: 28565758]
[22]
Chen X, Zou D, Chen X, Wu H, Xu D. Hesperetin inhibits foam cell formation and promotes cholesterol efflux in THP-1-derived macrophages by activating LXRα signal in an AMPK-dependent manner. J Physiol Biochem 2021; 77(3): 405-17.
[http://dx.doi.org/10.1007/s13105-020-00783-9] [PMID: 34212313]
[23]
Jia Q, Cao H, Shen D, et al. Quercetin protects against atherosclerosis by regulating the expression of PCSK9, CD36, PPARγ, LXRα and ABCA1. Int J Mol Med 2019; 44(3): 893-902.
[http://dx.doi.org/10.3892/ijmm.2019.4263] [PMID: 31524223]
[24]
Li B, Ji Y, Yi C, et al. Rutin inhibits Ox-LDL-mediated macrophage inflammation and foam cell formation by inducing autophagy and modulating PI3K/ATK signaling. Molecules 2022; 27(13): 4201.
[http://dx.doi.org/10.3390/molecules27134201] [PMID: 35807447]
[25]
Zhong H, Qiu J, Wu H, Xu H, Zhang P, Xue C, et al. Mechanism of action of trichosanthis fructus-allii macrostemonis bulbus herb pairs against hyperlipidemia based on network pharmacology. Zhongguo Shiyan Fangjixue Zazhi 2020; 26(18): 164-5.
[26]
Ding Y, Peng Y, Shen H, Shu L, Wei Y. Gualou Xiebai decoction inhibits cardiac dysfunction and inflammation in cardiac fibrosis rats. BMC Complement Altern Med 2015; 16(1): 49.
[http://dx.doi.org/10.1186/s12906-016-1012-5] [PMID: 26846090]
[27]
Song W, Wang W, Wang Y, Dou L, Chen L, Yan X. Characterization of fluorescent NBD-cholesterol efflux in THP-1-derived macrophages. Mol Med Rep 2015; 12(4): 5989-96.
[http://dx.doi.org/10.3892/mmr.2015.4154] [PMID: 26239480]
[28]
Li Y, Zhang L, Ren P, et al. Qing-Xue-Xiao-Zhi formula attenuates atherosclerosis by inhibiting macrophage lipid accumulation and inflammatory response via TLR4/MyD88/NF-κB pathway regulation. Phytomedicine 2021; 93: 153812.
[http://dx.doi.org/10.1016/j.phymed.2021.153812] [PMID: 34753029]
[29]
Raposeiras-Roubin S, Rosselló X, Oliva B, et al. Triglycerides and residual atherosclerotic risk. J Am Coll Cardiol 2021; 77(24): 3031-41.
[http://dx.doi.org/10.1016/j.jacc.2021.04.059] [PMID: 34140107]
[30]
Li J, Meng Q, Fu Y, et al. Novel insights: Dynamic foam cells derived from the macrophage in atherosclerosis. J Cell Physiol 2021; 236(9): 6154-67.
[http://dx.doi.org/10.1002/jcp.30300] [PMID: 33507545]
[31]
Ouimet M, Barrett TJ, Fisher EA. HDL and reverse cholesterol transport. Circ Res 2019; 124(10): 1505-18.
[http://dx.doi.org/10.1161/CIRCRESAHA.119.312617] [PMID: 31071007]
[32]
Xue H, Chen X, Yu C, et al. Gut microbially produced indole-3-propionic acid inhibits atherosclerosis by promoting reverse cholesterol transport and its deficiency is causally related to atherosclerotic cardiovascular disease. Circ Res 2022; 131(5): 404-20.
[http://dx.doi.org/10.1161/CIRCRESAHA.122.321253] [PMID: 35893593]
[33]
Li Y, Luo X, Hua Z, et al. Apolipoproteins as potential communicators play an essential role in the pathogenesis and treatment of early atherosclerosis. Int J Biol Sci 2023; 19(14): 4493-510.
[http://dx.doi.org/10.7150/ijbs.86475] [PMID: 37781031]
[34]
Yu XH, Zhang DW, Zheng XL, Tang CK. Cholesterol transport system: An integrated cholesterol transport model involved in atherosclerosis. Prog Lipid Res 2019; 73: 65-91.
[http://dx.doi.org/10.1016/j.plipres.2018.12.002] [PMID: 30528667]
[35]
Steck TL, Lange Y. Is reverse cholesterol transport regulated by active cholesterol? J Lipid Res 2023; 64(6): 100385.
[http://dx.doi.org/10.1016/j.jlr.2023.100385] [PMID: 37169287]
[36]
Chistiakov DA, Bobryshev YV, Orekhov AN. Macrophage‐mediated cholesterol handling in atherosclerosis. J Cell Mol Med 2016; 20(1): 17-28.
[http://dx.doi.org/10.1111/jcmm.12689] [PMID: 26493158]
[37]
Chen Z, Ying X, Meng S, et al. High-performance liquid chromatographic determination and pharmacokinetic study of apigenin-7-O-β-D-glucoside in rat plasma after intravenous administration. Arch Pharm Res 2011; 34(5): 741-6.
[http://dx.doi.org/10.1007/s12272-011-0507-3] [PMID: 21656359]
[38]
Ulusoy HG, Sanlier N. A minireview of quercetin: From its metabolism to possible mechanisms of its biological activities. Crit Rev Food Sci Nutr 2020; 60(19): 3290-303.
[http://dx.doi.org/10.1080/10408398.2019.1683810] [PMID: 31680558]
[39]
Chen IL, Tsai YJ, Huang CM, Tsai TH. Lymphatic absorption of quercetin and rutin in rat and their pharmacokinetics in systemic plasma. J Agric Food Chem 2010; 58(1): 546-51.
[http://dx.doi.org/10.1021/jf9026124] [PMID: 19916501]
[40]
Zheng S, Huang H, Li Y, et al. Yin-xing-tong-mai decoction attenuates atherosclerosis via activating PPARγ-LXRα-ABCA1/ABCG1 pathway. Pharmacol Res 2021; 169: 105639.
[http://dx.doi.org/10.1016/j.phrs.2021.105639] [PMID: 33932607]
[41]
Wang B, Tontonoz P. Liver X receptors in lipid signalling and membrane homeostasis. Nat Rev Endocrinol 2018; 14(8): 452-63.
[http://dx.doi.org/10.1038/s41574-018-0037-x] [PMID: 29904174]
[42]
Gao Q, Wei A, Chen F, et al. Enhancing PPARγ by HDAC inhibition reduces foam cell formation and atherosclerosis in ApoE deficient mice. Pharmacol Res 2020; 160: 105059.
[http://dx.doi.org/10.1016/j.phrs.2020.105059] [PMID: 32621955]
[43]
Montaigne D, Butruille L, Staels B. PPAR control of metabolism and cardiovascular functions. Nat Rev Cardiol 2021; 18(12): 809-23.
[http://dx.doi.org/10.1038/s41569-021-00569-6] [PMID: 34127848]
[44]
Wang H, Yang Y, Sun X, et al. Sonodynamic therapy-induced foam cells apoptosis activates the phagocytic PPARγ-LXRα-ABCA1/ABCG1 pathway and promotes cholesterol efflux in advanced plaque. Theranostics 2018; 8(18): 4969-84.
[http://dx.doi.org/10.7150/thno.26193] [PMID: 30429880]
[45]
Thacker SG, Rousset X, Esmail S, et al. Increased plasma cholesterol esterification by LCAT reduces diet-induced atherosclerosis in SR-BI knockout mice. J Lipid Res 2015; 56(7): 1282-95.
[http://dx.doi.org/10.1194/jlr.M048629] [PMID: 25964513]
[46]
Guo M, Liu Z, Xu Y, et al. Spontaneous atherosclerosis in aged LCAT-deficient hamsters with enhanced oxidative stress—brief report. Arterioscler Thromb Vasc Biol 2020; 40(12): 2829-36.
[http://dx.doi.org/10.1161/ATVBAHA.120.315265] [PMID: 32998519]
[47]
Getz G, Reardon C. Apoprotein E and reverse cholesterol transport. Int J Mol Sci 2018; 19(11): 3479.
[http://dx.doi.org/10.3390/ijms19113479] [PMID: 30404132]
[48]
Mineo C. Lipoprotein receptor signalling in atherosclerosis. Cardiovasc Res 2020; 116(7): 1254-74.
[http://dx.doi.org/10.1093/cvr/cvz338] [PMID: 31834409]
[49]
Ge M, Shao R, He H. Advances in understanding the regulatory mechanism of cholesterol 7α-hydroxylase. Biochem Pharmacol 2019; 164: 152-64.
[http://dx.doi.org/10.1016/j.bcp.2019.04.008] [PMID: 30978324]
[50]
Liu L, Zhao Y, Ming J, et al. Polyphenol extract and essential oil of Amomum tsao-ko equally alleviate hypercholesterolemia and modulate gut microbiota. Food Funct 2021; 12(23): 12008-21.
[http://dx.doi.org/10.1039/D1FO03082E] [PMID: 34755750]
[51]
Ren K, Jiang T, Zhou HF, Liang Y, Zhao GJ. Apigenin retards atherogenesis by promoting ABCA1-mediated cholesterol efflux and suppressing inflammation. Cell Physiol Biochem 2018; 47(5): 2170-84.
[http://dx.doi.org/10.1159/000491528] [PMID: 29975943]
[52]
Ballerini P, Ciccarelli R, Di Iorio P, et al. Guanosine effect on cholesterol efflux and apolipoprotein E expression in astrocytes. Purinergic Signal 2006; 2(4): 637-49.
[http://dx.doi.org/10.1007/s11302-006-9011-5] [PMID: 18404467]
[53]
Leiva A, Guzmán-Gutiérrez E, Contreras-Duarte S, et al. Adenosine receptors: Modulators of lipid availability that are controlled by lipid levels. Mol Aspects Med 2017; 55: 26-44.
[http://dx.doi.org/10.1016/j.mam.2017.01.007] [PMID: 28153452]
[54]
Li Y, Qin R, Yan H, et al. Inhibition of vascular smooth muscle cells premature senescence with rutin attenuates and stabilizes diabetic atherosclerosis. J Nutr Biochem 2018; 51: 91-8.
[http://dx.doi.org/10.1016/j.jnutbio.2017.09.012] [PMID: 29107826]
[55]
Xie W, Zhang Y, Wang N, et al. Novel effects of macrostemonoside A, a compound from Allium macrostemon Bung, on hyperglycemia, hyperlipidemia, and visceral obesity in high-fat diet-fed C57BL/6 mice. Eur J Pharmacol 2008; 599(1-3): 159-65.
[http://dx.doi.org/10.1016/j.ejphar.2008.09.042] [PMID: 18930725]

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