Skip to content
2000
Volume 21, Issue 2
  • ISSN: 1567-2026
  • E-ISSN: 1875-5739

Abstract

Background

Gualou is derived from the fruit of Maxim, while Xiebai from the bulbs of 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. 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) oral gavage. Besides, RAW264.7 macrophages were stimulated by ox-LDL to establish a foam cell model .

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.

Loading

Article metrics loading...

/content/journals/cnr/10.2174/0115672026308438240405055719
2024-04-15
2025-01-24
Loading full text...

Full text loading...

References

  1. PerrottaI. Atherosclerosis: From molecular biology to therapeutic perspective 3.0.Int. J. Mol. Sci.2023248689710.3390/ijms24086897 37108058
    [Google Scholar]
  2. KolaszyńskaO. LorkowskiJ. Symmetry and asymmetry in atherosclerosis.Int. J. Occup. Med. Environ. Health202336669370310.13075/ijomeh.1896.02171 37791506
    [Google Scholar]
  3. LibbyP. BuringJ.E. BadimonL. Atherosclerosis.Nat. Rev. Dis. Primers2019515610.1038/s41572‑019‑0106‑z 31420554
    [Google Scholar]
  4. ArvanitisM. LowensteinC.J. Dyslipidemia.Ann. Intern. Med.20231766ITC81ITC9610.7326/AITC202306200 37307585
    [Google Scholar]
  5. DelialisD. GeorgiopoulosG. AivaliotiE. Remnant cholesterol and atherosclerotic disease in high cardiovascular risk patients. Beyond LDL cholesterol and hypolipidemic treatment.Hellenic J. Cardiol.202266263110.1016/j.hjc.2022.05.011 35667617
    [Google Scholar]
  6. WadströmB.N. PedersenK.M. WulffA.B. NordestgaardB.G. Elevated remnant cholesterol, plasma triglycerides, and cardiovascular and non-cardiovascular mortality.Eur. Heart J.202344161432144510.1093/eurheartj/ehac822 36631967
    [Google Scholar]
  7. GasbarrinoK. HafianeA. GianopoulosI. ZhengH. MantzorosC.S. DaskalopoulouS.S. Relationship between circulating adipokines and cholesterol efflux in subjects with severe carotid atherosclerosis.Metabolism202314015538110.1016/j.metabol.2022.155381 36566801
    [Google Scholar]
  8. RohatgiA. Reverse cholesterol transport and atherosclerosis.Arterioscler. Thromb. Vasc. Biol.20193912410.1161/ATVBAHA.118.311978 30586333
    [Google Scholar]
  9. XieJ PengL wang T, et al. QiShenYiQi pill inhibits atherosclerosis by promoting reverse cholesterol transport PPARγ-LXRα/β-ABCA1 pathway.J. Ethnopharmacol.202331511668410.1016/j.jep.2023.116684
    [Google Scholar]
  10. PownallH.J. RosalesC. GillardB.K. GottoA.M.Jr High-density lipoproteins, reverse cholesterol transport and atherogenesis.Nat. Rev. Cardiol.2021181071272310.1038/s41569‑021‑00538‑z 33833449
    [Google Scholar]
  11. PengY. XuJ. ZengY. ChenL. XuX.L. Polydatin attenuates atherosclerosis in apolipoprotein E-deficient mice: Role of reverse cholesterol transport.Phytomedicine20196215293510.1016/j.phymed.2019.152935 31085374
    [Google Scholar]
  12. FloresR. JinX. ChangJ. LCAT, ApoD, and ApoA1 expression and review of cholesterol deposition in the cornea.Biomolecules201991278510.3390/biom9120785 31779197
    [Google Scholar]
  13. LiuY. ZhongH. XuP. Deciphering the combination mechanisms of Gualou–Xiebai herb pair against atherosclerosis by network pharmacology and HPLC-Q-TOF-MS technology.Front. Pharmacol.20221394140010.3389/fphar.2022.941400 36120369
    [Google Scholar]
  14. ZhangW.Y. YuY. YanL.L. Discovery of cardio-protective constituents of gualou xiebai decoction, a classical traditional Chinese medicinal formula.Phytomedicine20195431832710.1016/j.phymed.2018.04.047 30060904
    [Google Scholar]
  15. WuR. LiuX. WangJ. ZhouX.Z. Study on law using Chinese drug of famous old docter of traditional Chinese medicine to coronary heart disease based on association rules.Zhongguo Zhongyao Zazhi2007321717861788 17993003
    [Google Scholar]
  16. LuX. XuH. ZhaoT. LiG. 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.2018241290591110.1007/s11655‑018‑2564‑7 29948595
    [Google Scholar]
  17. DingL. XuP. BaoY. HuangJ. WuH. Effects of trichosanthis fructus-allii macrostemonis bulbus on the activation of NLRP3 inflammasomes in ApoE-/- mice at different stages of atherosclerosis.Chinese Journal of Atherosclerosis20223019
    [Google Scholar]
  18. LuoM. FanR. WangX. Gualou xiebai banxia decoction ameliorates poloxamer 407-induced hyperlipidemia.Biosci. Rep.2021416BSR2020421610.1042/BSR20204216 34036306
    [Google Scholar]
  19. YanL.L. ZhangW.Y. WeiX.H. Gualou xiebai decoction, a traditional chinese medicine, prevents cardiac reperfusion injury of hyperlipidemia rat via energy modulation.Front. Physiol.2018929610.3389/fphys.2018.00296 29674972
    [Google Scholar]
  20. XuP.B. DingL.D. QiuJ.W. Study on effect of “Trichosanthis Fructus-Allii Macrostemonis Bulbus” on atherosclerosis in ApoE~(-/-) mice based on liver metabonomics.Zhongguo Zhongyao Zazhi2021462053205329 34738436
    [Google Scholar]
  21. ZhangK. SongW. LiD. JinX. Apigenin in the regulation of cholesterol metabolism and protection of blood vessels.Exp. Ther. Med.20171351719172410.3892/etm.2017.4165 28565758
    [Google Scholar]
  22. ChenX. ZouD. ChenX. WuH. XuD. 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.202177340541710.1007/s13105‑020‑00783‑9 34212313
    [Google Scholar]
  23. JiaQ. CaoH. ShenD. Quercetin protects against atherosclerosis by regulating the expression of PCSK9, CD36, PPARγ, LXRα and ABCA1.Int. J. Mol. Med.201944389390210.3892/ijmm.2019.4263 31524223
    [Google Scholar]
  24. LiB. JiY. YiC. Rutin inhibits Ox-LDL-mediated macrophage inflammation and foam cell formation by inducing autophagy and modulating PI3K/ATK signaling.Molecules20222713420110.3390/molecules27134201 35807447
    [Google Scholar]
  25. ZhongH. QiuJ. WuH. XuH. ZhangP. XueC. Mechanism of action of trichosanthis fructus-allii macrostemonis bulbus herb pairs against hyperlipidemia based on network pharmacology.Zhongguo Shiyan Fangjixue Zazhi20202618164165
    [Google Scholar]
  26. DingY. PengY. ShenH. ShuL. WeiY. Gualou Xiebai decoction inhibits cardiac dysfunction and inflammation in cardiac fibrosis rats.BMC Complement. Altern. Med.20151614910.1186/s12906‑016‑1012‑5 26846090
    [Google Scholar]
  27. SongW. WangW. WangY. DouL. ChenL. YanX. Characterization of fluorescent NBD-cholesterol efflux in THP-1-derived macrophages.Mol. Med. Rep.20151245989599610.3892/mmr.2015.4154 26239480
    [Google Scholar]
  28. LiY. ZhangL. RenP. Qing-Xue-Xiao-Zhi formula attenuates atherosclerosis by inhibiting macrophage lipid accumulation and inflammatory response via TLR4/MyD88/NF-κB pathway regulation.Phytomedicine20219315381210.1016/j.phymed.2021.153812 34753029
    [Google Scholar]
  29. Raposeiras-RoubinS. RossellóX. OlivaB. Triglycerides and residual atherosclerotic risk.J. Am. Coll. Cardiol.202177243031304110.1016/j.jacc.2021.04.059 34140107
    [Google Scholar]
  30. LiJ. MengQ. FuY. Novel insights: Dynamic foam cells derived from the macrophage in atherosclerosis.J. Cell. Physiol.202123696154616710.1002/jcp.30300 33507545
    [Google Scholar]
  31. OuimetM. BarrettT.J. FisherE.A. HDL and reverse cholesterol transport.Circ. Res.2019124101505151810.1161/CIRCRESAHA.119.312617 31071007
    [Google Scholar]
  32. XueH. ChenX. YuC. 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.2022131540442010.1161/CIRCRESAHA.122.321253 35893593
    [Google Scholar]
  33. LiY. LuoX. HuaZ. Apolipoproteins as potential communicators play an essential role in the pathogenesis and treatment of early atherosclerosis.Int. J. Biol. Sci.202319144493451010.7150/ijbs.86475 37781031
    [Google Scholar]
  34. YuX.H. ZhangD.W. ZhengX.L. TangC.K. Cholesterol transport system: An integrated cholesterol transport model involved in atherosclerosis.Prog. Lipid Res.201973659110.1016/j.plipres.2018.12.002 30528667
    [Google Scholar]
  35. SteckT.L. LangeY. Is reverse cholesterol transport regulated by active cholesterol?J. Lipid Res.202364610038510.1016/j.jlr.2023.100385 37169287
    [Google Scholar]
  36. ChistiakovD.A. BobryshevY.V. OrekhovA.N. Macrophage‐mediated cholesterol handling in atherosclerosis.J. Cell. Mol. Med.2016201172810.1111/jcmm.12689 26493158
    [Google Scholar]
  37. ChenZ. YingX. MengS. High-performance liquid chromatographic determination and pharmacokinetic study of apigenin-7-O-β-D-glucoside in rat plasma after intravenous administration.Arch. Pharm. Res.201134574174610.1007/s12272‑011‑0507‑3 21656359
    [Google Scholar]
  38. UlusoyH.G. SanlierN. A minireview of quercetin: From its metabolism to possible mechanisms of its biological activities.Crit. Rev. Food Sci. Nutr.202060193290330310.1080/10408398.2019.1683810 31680558
    [Google Scholar]
  39. ChenI.L. TsaiY.J. HuangC.M. TsaiT.H. Lymphatic absorption of quercetin and rutin in rat and their pharmacokinetics in systemic plasma.J. Agric. Food Chem.201058154655110.1021/jf9026124 19916501
    [Google Scholar]
  40. ZhengS. HuangH. LiY. Yin-xing-tong-mai decoction attenuates atherosclerosis via activating PPARγ-LXRα-ABCA1/ABCG1 pathway.Pharmacol. Res.202116910563910.1016/j.phrs.2021.105639 33932607
    [Google Scholar]
  41. WangB. TontonozP. Liver X receptors in lipid signalling and membrane homeostasis.Nat. Rev. Endocrinol.201814845246310.1038/s41574‑018‑0037‑x 29904174
    [Google Scholar]
  42. GaoQ. WeiA. ChenF. Enhancing PPARγ by HDAC inhibition reduces foam cell formation and atherosclerosis in ApoE deficient mice.Pharmacol. Res.202016010505910.1016/j.phrs.2020.105059 32621955
    [Google Scholar]
  43. MontaigneD. ButruilleL. StaelsB. PPAR control of metabolism and cardiovascular functions.Nat. Rev. Cardiol.2021181280982310.1038/s41569‑021‑00569‑6 34127848
    [Google Scholar]
  44. WangH. YangY. SunX. Sonodynamic therapy-induced foam cells apoptosis activates the phagocytic PPARγ-LXRα-ABCA1/ABCG1 pathway and promotes cholesterol efflux in advanced plaque.Theranostics20188184969498410.7150/thno.26193 30429880
    [Google Scholar]
  45. ThackerS.G. RoussetX. EsmailS. Increased plasma cholesterol esterification by LCAT reduces diet-induced atherosclerosis in SR-BI knockout mice.J. Lipid Res.20155671282129510.1194/jlr.M048629 25964513
    [Google Scholar]
  46. GuoM. LiuZ. XuY. Spontaneous atherosclerosis in aged LCAT-deficient hamsters with enhanced oxidative stress—brief report.Arterioscler. Thromb. Vasc. Biol.202040122829283610.1161/ATVBAHA.120.315265 32998519
    [Google Scholar]
  47. GetzG. ReardonC. Apoprotein E and reverse cholesterol transport.Int. J. Mol. Sci.20181911347910.3390/ijms19113479 30404132
    [Google Scholar]
  48. MineoC. Lipoprotein receptor signalling in atherosclerosis.Cardiovasc. Res.202011671254127410.1093/cvr/cvz338 31834409
    [Google Scholar]
  49. GeM. ShaoR. HeH. Advances in understanding the regulatory mechanism of cholesterol 7α-hydroxylase.Biochem. Pharmacol.201916415216410.1016/j.bcp.2019.04.008 30978324
    [Google Scholar]
  50. LiuL. ZhaoY. MingJ. Polyphenol extract and essential oil of Amomum tsao-ko equally alleviate hypercholesterolemia and modulate gut microbiota.Food Funct.20211223120081202110.1039/D1FO03082E 34755750
    [Google Scholar]
  51. RenK. JiangT. ZhouH.F. LiangY. ZhaoG.J. Apigenin retards atherogenesis by promoting ABCA1-mediated cholesterol efflux and suppressing inflammation.Cell. Physiol. Biochem.20184752170218410.1159/000491528 29975943
    [Google Scholar]
  52. BalleriniP. CiccarelliR. Di IorioP. Guanosine effect on cholesterol efflux and apolipoprotein E expression in astrocytes.Purinergic Signal.20062463764910.1007/s11302‑006‑9011‑5 18404467
    [Google Scholar]
  53. LeivaA. Guzmán-GutiérrezE. Contreras-DuarteS. Adenosine receptors: Modulators of lipid availability that are controlled by lipid levels.Mol. Aspects Med.201755264410.1016/j.mam.2017.01.007 28153452
    [Google Scholar]
  54. LiY. QinR. YanH. Inhibition of vascular smooth muscle cells premature senescence with rutin attenuates and stabilizes diabetic atherosclerosis.J. Nutr. Biochem.201851919810.1016/j.jnutbio.2017.09.012 29107826
    [Google Scholar]
  55. XieW. ZhangY. WangN. 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.20085991-315916510.1016/j.ejphar.2008.09.042 18930725
    [Google Scholar]
/content/journals/cnr/10.2174/0115672026308438240405055719
Loading
/content/journals/cnr/10.2174/0115672026308438240405055719
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test