Skip to content
2000
Volume 17, Issue 1
  • ISSN: 1874-4672
  • E-ISSN: 1874-4702

Abstract

Background and Aims

Atherosclerosis is a chronic cardiovascular disease which is regarded as one of the most common causes of death in the elderly. Recent evidence has shown that atherosclerotic patients can benefit by targeting interleukin-1 beta (IL-1β). Aloperine (ALO) is an alkaloid which is mainly isolated from L. and has been recognized as an anti-inflammatory disease. Herein, the effect of ALO on atherosclerosis was investigated.

Methods

ApoE-/- mice fed with western diet received ALO once daily. Plaques in the aortas were evaluated using oil red O and hematoxylin & eosin (H&E) staining. Inflammation, lipids and kinases phosphorylation levels were evaluated using ELISA assay and western blot. Pyroptosis was examined by THP-1 cells treated with oxidized low-density lipoprotein (ox-LDL).

Results

Plaque development in aortic sinus and aortas were reduced after ALO treatment in ApoE-/- miceTreatment with ALO ameliorated inflammation and profile of blood lipid. Western blot assay showed that ALO treatment substantially inhibited phosphorylation of p38 and Jun N-terminal kinase (JNK) in aorta of ApoE-/- mice. Meanwhile, ALO significantly inhibited levels of IL-1β and IL-18 in serum and cleaved caspase-1 and IL-1β expression in aorta of ApoE-/- mice. Interestingly, ALO mildly increased pro-caspase-1 expression in ApoE-/- aorta in comparison with saline group. In a dose dependent fashion, ALO treatment markedly inhibited ox-LDL-induced IL-1β and IL-18 levels in THP-1 cells and reduced cleaved caspase-1 and IL-1β expression and caspase-1 activity, while ALO had little effect on nod-like receptor protein containing pyrin-3 (NLRP3), apoptosis associated speck-like protein containing a caspase-1 recruitment domain (ASC).

Conclusion

It is of great practical significance to find the natural product to regulate macrophage pyroptosis, which are key drivers to accelerate the progression of atherosclerosis. ALO could inhibit NLRP3 inflammasome activation in macrophages during atherogenesis, which may serve as a potential candidate for the treatment of atherosclerosis.

This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Loading

Article metrics loading...

/content/journals/cmp/10.2174/0118761429342447241214044859
2024-01-01
2025-07-13
The full text of this item is not currently available.

References

  1. HerringtonW. LaceyB. SherlikerP. ArmitageJ. LewingtonS. Epidemiology of atherosclerosis and the potential to reduce the global burden of atherothrombotic disease.Circ. Res.2016118453554610.1161/CIRCRESAHA.115.30761126892956
    [Google Scholar]
  2. FanJ. WatanabeT. Atherosclerosis: Known and unknown.Pathol. Int.202272315116010.1111/pin.1320235076127
    [Google Scholar]
  3. LibbyP. The changing landscape of atherosclerosis.Nature2021592785552453310.1038/s41586‑021‑03392‑833883728
    [Google Scholar]
  4. YuP. ZhangX. LiuN. TangL. PengC. ChenX. Pyroptosis: Mechanisms and diseases.Signal Transduct. Target. Ther.20216112810.1038/s41392‑021‑00507‑533776057
    [Google Scholar]
  5. XiaoC. CaoS. LiY. LuoY. LiuJ. ChenY. BaiQ. ChenL. Pyroptosis in microbial infectious diseases.Mol. Biol. Rep.20245114210.1007/s11033‑023‑09078‑w38158461
    [Google Scholar]
  6. Al MamunA. WuY. MonalisaI. JiaC. ZhouK. MunirF. XiaoJ. Role of pyroptosis in spinal cord injury and its therapeutic implications.J. Adv. Res.2021289710910.1016/j.jare.2020.08.00433364048
    [Google Scholar]
  7. XuY. J. ZhengL. HuY. W. WangQ. Pyroptosis and its relationship to atherosclerosis.Clin. Chim. Acta2018476283710.1016/j.cca.2017.11.005
    [Google Scholar]
  8. FalkE. Pathogenesis of atherosclerosis.J. Am. Coll. Cardiol.2006478Suppl.C7C1210.1016/j.jacc.2005.09.06816631513
    [Google Scholar]
  9. WeiY. LanB. ZhengT. YangL. ZhangX. ChengL. TuerhongjiangG. YuanZ. WuY. GSDME-mediated pyroptosis promotes the progression and associated inflammation of atherosclerosis.Nat. Commun.202314192910.1038/s41467‑023‑36614‑w36807553
    [Google Scholar]
  10. HeX. FanX. BaiB. LuN. ZhangS. ZhangL. Pyroptosis is a critical immune-inflammatory response involved in atherosclerosis.Pharmacol. Res.202116510544710.1016/j.phrs.2021.10544733516832
    [Google Scholar]
  11. ZhangY. LiuX. BaiX. LinY. LiZ. FuJ. LiM. ZhaoT. YangH. XuR. LiJ. JuJ. CaiB. XuC. YangB. Melatonin prevents endothelial cell pyroptosis via regulation of long noncoding RNA MEG3/miR-223/NLRP3 axis.J. Pineal Res.2018642e1244910.1111/jpi.1244929024030
    [Google Scholar]
  12. HuQ. ZhangT. YiL. ZhouX. MiM. Dihydromyricetin inhibits NLRP3 inflammasome-dependent pyroptosis by activating the Nrf2 signaling pathway in vascular endothelial cells.Biofactors201844212313610.1002/biof.139529193391
    [Google Scholar]
  13. MengQ. LiY. JiT. ChaoY. LiJ. FuY. WangS. ChenQ. ChenW. HuangF. WangY. ZhangQ. WangX. BianH. Estrogen prevent atherosclerosis by attenuating endothelial cell pyroptosis via activation of estrogen receptor α-mediated autophagy.J. Adv. Res.20212814916410.1016/j.jare.2020.08.01033364052
    [Google Scholar]
  14. YuanJ. FuY. FengZ. SangF. ShaoM. LiL. Potential mechanisms and effects of chinese medicines in treatment of diabetic atherosclerosis by modulating NLRP3 inflammasome: A narrative review.Chin. J. Integr. Med.202228875376110.1007/s11655‑022‑3513‑435507299
    [Google Scholar]
  15. ChengY. RaufA. PanX. Research progress on the natural product aloperine and its derivatives.Mini Rev. Med. Chem.202222572974210.2174/138955752166621083115542634488611
    [Google Scholar]
  16. DangZ. ZhuL. LaiW. BogerdH. LeeK.H. HuangL. ChenC.H. Aloperine and its derivatives as a new class of HIV-1 entry inhibitors.ACS Med. Chem. Lett.20167324024410.1021/acsmedchemlett.5b0033926985308
    [Google Scholar]
  17. WuF. Protective effects of aloperine on monocrotaline-induced pulmonary hypertension in rats.Biomed. Pharmacother.20178963264110.1016/j.biopha.2017.02.033
    [Google Scholar]
  18. HuR. ChenL. ChenX. XieZ. XiaC. ChenY. Aloperine improves osteoporosis in ovariectomized mice by inhibiting RANKL-induced NF-κB, ERK and JNK approaches.Int. Immunopharmacol.20219710772010.1016/j.intimp.2021.10772033945918
    [Google Scholar]
  19. YeY. WangY. YangY. TaoL. Aloperine suppresses LPS-induced macrophage activation through inhibiting the TLR4/NF-κB pathway.Inflamm. Res.20206937538310.1007/s00011‑019‑01313‑0
    [Google Scholar]
  20. YuH.I. ShenH.C. ChenS.H. LimY.P. ChuangH.H. TaiT.S. KungF.P. LuC.H. HouC.Y. LeeY.R. Autophagy modulation in human thyroid cancer cells following aloperine treatment.Int. J. Mol. Sci.20192021531510.3390/ijms2021531531731481
    [Google Scholar]
  21. XiongR. ShanS. WangX. ZhangX. YuH. ShiH. WangX. Aloperine attenuates carbon tetrachloride-induced mouse hepatic injury via Nrf2/HO-1 pathway.Trop. J. Pharm. Res.202019598398810.4314/tjpr.v19i5.11
    [Google Scholar]
  22. ZhaoJ. Neuro-protective effects of aloperine in an Alzheimer's disease cellular model.Biomed. Pharmacother.201810813714310.1016/j.biopha.2018.09.008
    [Google Scholar]
  23. FuX. SunF. WangF. ZhangJ. ZhengB. ZhongJ. YueT. ZhengX. XuJ.F. WangC.Y. Aloperine protects mice against dss-induced colitis by PP2A-mediated PI3K/Akt/mTOR signaling suppression.Mediators Inflamm.2017201711410.1155/2017/570615229056830
    [Google Scholar]
  24. WangC. ChoiY.H. XianZ. ZhengM. PiaoH. YanG. Aloperine suppresses allergic airway inflammation through NF-κB, MAPK, and Nrf2/HO-1 signaling pathways in mice.Int. Immunopharmacol.20186557157910.1016/j.intimp.2018.11.00330415164
    [Google Scholar]
  25. CuiY.R. QuF. ZhongW.J. YangH.H. ZengJ. HuangJ.H. LiuJ. ZhangM.Y. ZhouY. GuanC.X. Beneficial effects of aloperine on inflammation and oxidative stress by suppressing necroptosis in lipopolysaccharide-induced acute lung injury mouse model.Phytomedicine202210015407410.1016/j.phymed.2022.15407435397283
    [Google Scholar]
  26. ZengJ. LiuJ. HuangJ.H. FuS.P. WangX.Y. XiC. CuiY.R. QuF. Aloperine alleviates lipopolysaccharide-induced acute lung injury by inhibiting NLRP3 inflammasome activation.Int. Immunopharmacol.202312011014210.1016/j.intimp.2023.11014237210910
    [Google Scholar]
  27. LiW. LiY. ZhaoY. RenL. The protective effects of aloperine against ox-LDL-induced endothelial dysfunction and inflammation in HUVECs.Artif. Cells Nanomed. Biotechnol.202048110711510.1080/21691401.2019.169981631852304
    [Google Scholar]
  28. YinW. HanJ. ZhangZ. HanZ. WangS. Aloperine protects mice against bleomycin-induced pulmonary fibrosis by attenuating fibroblast proliferation and differentiation.Sci. Rep.201881626510.1038/s41598‑018‑24565‑y29674691
    [Google Scholar]
  29. LusisA.J. Atherosclerosis.Nature2000407680123324110.1038/3502520311001066
    [Google Scholar]
  30. SoehnleinO. LibbyP. Targeting inflammation in atherosclerosis — From experimental insights to the clinic.Nat. Rev. Drug Discov.202120858961010.1038/s41573‑021‑00198‑133976384
    [Google Scholar]
  31. GimbroneM.A.Jr García-CardeñaG. Endothelial cell dysfunction and the pathobiology of atherosclerosis.Circ. Res.2016118462063610.1161/CIRCRESAHA.115.30630126892962
    [Google Scholar]
  32. SageA.P. TsiantoulasD. BinderC.J. MallatZ. The role of B cells in atherosclerosis.Nat. Rev. Cardiol.201916318019610.1038/s41569‑018‑0106‑930410107
    [Google Scholar]
  33. GisteråA. HanssonG.K. The immunology of atherosclerosis.Nat. Rev. Nephrol.201713636838010.1038/nrneph.2017.5128392564
    [Google Scholar]
  34. RobbinsC.S. HilgendorfI. WeberG.F. TheurlI. IwamotoY. FigueiredoJ.L. GorbatovR. SukhovaG.K. GerhardtL.M.S. SmythD. ZavitzC.C.J. ShikataniE.A. ParsonsM. van RooijenN. LinH.Y. HusainM. LibbyP. NahrendorfM. WeisslederR. SwirskiF.K. Local proliferation dominates lesional macrophage accumulation in atherosclerosis.Nat. Med.20131991166117210.1038/nm.325823933982
    [Google Scholar]
  35. GrebeA. HossF. LatzE. NLRP3 inflammasome and the IL-1 pathway in atherosclerosis.Circ. Res.2018122121722174010.1161/CIRCRESAHA.118.31136229880500
    [Google Scholar]
  36. KelleyN. JeltemaD. DuanY. HeY. The NLRP3 inflammasome: An overview of mechanisms of activation and regulation.Int. J. Mol. Sci.20192013332810.3390/ijms2013332831284572
    [Google Scholar]
  37. AtanasovA.G. ZotchevS.B. DirschV.M. SupuranC.T. International Natural Product Sciences Taskforce Natural products in drug discovery: Advances and opportunities.Nat. Rev. Drug Discov.202120320021610.1038/s41573‑020‑00114‑z33510482
    [Google Scholar]
  38. ZhangX. WangZ. LiX. ChenJ. YuZ. LiX. SunC. HuL. WuM. LiuL. Polydatin protects against atherosclerosis by activating autophagy and inhibiting pyroptosis mediated by the NLRP3 inflammasome.J. Ethnopharmacol.202330911630410.1016/j.jep.2023.11630436870461
    [Google Scholar]
  39. LuoX. WengX. BaoX. BaiX. LvY. ZhangS. ChenY. ZhaoC. ZengM. HuangJ. XuB. JohnsonT.W. WhiteS.J. LiJ. JiaH. YuB. A novel anti-atherosclerotic mechanism of quercetin: Competitive binding to KEAP1 via Arg483 to inhibit macrophage pyroptosis.Redox Biol.20225710251110.1016/j.redox.2022.10251136274522
    [Google Scholar]
  40. ZhuY. LiaoH.L. WangN. FriedliO.Jr VernaL. StemermanM.B. Low-density lipoprotein activates Jun N-terminal kinase (JNK) in human endothelial cells.Biochim. Biophys. Acta Mol. Cell Biol. Lipids19991436355756410.1016/S0005‑2760(98)00167‑29989285
    [Google Scholar]
  41. ZhuY. LiaoH. WangN. MaK.S. VernaL.K. ShyyJ.Y.J. ChienS. StemermanM.B. LDL-activated p38 in endothelial cells is mediated by Ras.Arterioscler. Thromb. Vasc. Biol.20012171159116410.1161/hq0701.09247311451745
    [Google Scholar]
  42. LuoJ. WangX. JiangX. LiuC. LiY. HanX. ZuoX. LiY. LiN. XuY. SiS. Rutaecarpine derivative R3 attenuates atherosclerosis via inhibiting NLRP3 inflammasome-related inflammation and modulating cholesterol transport.FASEB J.20203411398141110.1096/fj.201900903RRR31914630
    [Google Scholar]
  43. GongL. LeiY. LiuY. TanF. LiS. WangX. XuM. CaiW. DuB. XuF. ZhouY. HanH. SunH. QiuL. Vaccarin prevents ox-LDL-induced HUVEC EndMT, inflammation and apoptosis by suppressing ROS/p38 MAPK signaling.Am. J. Transl. Res.20191142140215431105824
    [Google Scholar]
/content/journals/cmp/10.2174/0118761429342447241214044859
Loading
/content/journals/cmp/10.2174/0118761429342447241214044859
Loading

Data & Media loading...


  • Article Type:
    Research Article
Keyword(s): Aloperine; Atherosclerosis; Cardiovascular Disease; Macrophage; NLRP3; Pyroptosis
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