Skip to content
2000
Volume 17, Issue 1
  • ISSN: 1874-4672
  • E-ISSN: 1874-4702
file format pdf download PDF
file format text download EPUB
side by side viewer icon HTML

Abstract

Background

Chronic high-fat diets (HFDs) lead to an imbalance of calcium homeostasis in cardiomyocytes, which contributes to the development of myocardial ischemia-reperfusion injury, dilated cardiomyopathy, and other cardiovascular diseases. Aloe-emodin (AE) is an anthraquinone component isolated from aloe, rhubarb, and cassia seed, having cardiovascular protective, hepatoprotective, anti-inflammatory, and other pharmacological effects.

Objective

This study aimed to explore the specific role of AE in obesity/hyperlipidemia-induced myocardial intracellular calcium homeostasis imbalance.

Methods

Wistar rats (male, 220 ± 20 g) were fed HFD for four weeks and AE (100 mg/kg) was administrated for six weeks after confirmation of the HFD model. Serum lipids, reactive oxygen species levels, malondialdehyde levels, and superoxide dismutase levels were measured by commercial biochemical kits. Electrocardiograms of rats were recorded with the BL-420F biological function experimental system. Calcium transients and resting intracellular Ca2+ concentrations were determined by the Langendorff-perfused heart model. Protein levels of Ca2+/calmodulin-dependent protein kinase II (CaMKII), protein arginine methyltransferase 1 (PRMT1), and cardiac Ca2+ handling proteins were evaluated by western blot analysis.

Results

HFD-induced hearts exhibited a reduced amplitude of Ca2+ transients and increased resting levels of [Ca2+] in the heart; AE treatment significantly improved these parameters. Furthermore, the HFD-induced heart showed downregulation of PRMT1, upregulation of CaMKII, and abnormalities in the levels of Ca2+ handling proteins. All these deleterious changes were significantly suppressed by the AE treatment. Moreover, AE treatment prevented palmitic acid (PA)-induced calcium overload in H9C2 cells; this effect was reduced by the application of an inhibitor of PRMT1.

Conclusion

Taken together, this study demonstrates that AE could alleviate HFD/PA-induced myocardial intracellular calcium homeostasis imbalance via the PRMT1/CaMKII signaling pathway.

© 2024 The Author(s).
© 2024 The Author(s). Published by Bentham Science Publishers. This is an open access article published under CC BY 4.0 https://creativecommons.org/licenses/by/4.0/legalcode
Loading

Article metrics loading...

/content/journals/cmp/10.2174/0118761429364907250319054353
2024-01-01
2025-09-02

  • From This Site

    /content/journals/cmp/10.2174/0118761429364907250319054353
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

/deliver/fulltext/cmp/17/1/CMP-17-E18761429364907.html?itemId=/content/journals/cmp/10.2174/0118761429364907250319054353&mimeType=html&fmt=ahah

References

  1. BaiY. SuZ. SunH. ZhaoW. ChenX. HangP. ZhuW. DuZ. Aloe-emodin relieves high-fat diet induced qt prolongation via MiR-1 inhibition and IK1 up-regulation in rats.Cell. Physiol. Biochem.20174351961197310.1159/00048412029055952
     [Google Scholar]
  2. Carvalho-GontijoR. HanC. ZhangL. ZhangV. HosseiniM. MekeelK. SchnablB. LoombaR. KarinM. BrennerD.A. KisselevaT. Metabolic injury of hepatocytes promotes progression of NAFLD and AALD.Semin. Liver Dis.202242323324910.1055/s‑0042‑175531636001995
     [Google Scholar]
  3. YuC. WanX. LiD. GuoX. Reduction of obesity and hepatic adiposity in high-fat diet-induced rats by besunyen slimming tea.Heliyon202396e1738310.1016/j.heliyon.2023.e1738337416691
     [Google Scholar]
  4. ZhongP. QuanD. HuangY. HuangH. CaMKII activation promotes cardiac electrical remodeling and increases the susceptibility to arrhythmia induction in high-fat diet–fed mice with hyperlipidemia conditions.J. Cardiovasc. Pharmacol.201770424525410.1097/FJC.000000000000051228662005
     [Google Scholar]
  5. Zayas-ArrabalJ. AlquizaA. TuncayE. TuranB. GallegoM. CasisO. Molecular and electrophysiological role of diabetes-associated circulating inflammatory factors in cardiac arrhythmia remodeling in a metabolic-induced model of type 2 diabetic rat.Int. J. Mol. Sci.20212213682710.3390/ijms2213682734202017
     [Google Scholar]
  6. L’AbbateS. NicoliniG. ForiniF. MarchettiS. LascioD.N. FaitaF. KusmicC. Myo–inositol and d-chiro–inositol oral supplementation ameliorate cardiac dysfunction and remodeling in a mouse model of diet-induced obesity.Pharmacol. Res.202015910504710.1016/j.phrs.2020.10504732590101
     [Google Scholar]
  7. McCauleyM.D. HongL. SridharA. MenonA. PerikeS. ZhangM. SilvaD.I.B. YanJ. BoniniM.G. AiX. RehmanJ. DarbarD. Ion channel and structural remodeling in obesity-mediated atrial fibrillation.Circ. Arrhythm. Electrophysiol.2020138e00829610.1161/CIRCEP.120.00829632654503
     [Google Scholar]
  8. ZhongP. QuanD. PengJ. XiongX. LiuY. KongB. HuangH. Role of CaMKII in free fatty acid/hyperlipidemia-induced cardiac remodeling both in vitro and in vivo.J. Mol. Cell. Cardiol.201710911610.1016/j.yjmcc.2017.06.01028668302
     [Google Scholar]
  9. LiA. LianL. ChenX. CaiW. FanX. FanY. LiT. XieY. ZhangJ. The role of mitochondria in myocardial damage caused by energy metabolism disorders: From mechanisms to therapeutics.Free Radic. Biol. Med.202320823625110.1016/j.freeradbiomed.2023.08.00937567516
     [Google Scholar]
  10. TangX. ZhangY. LiuX. LiX. ZhaoH. CuiH. ShiY. ChenY. XuH. MengZ. ZhaoL. ChenH. WangZ. ZhuM. LinY. YangB. ZhangY. Aloe-emodin derivative produces anti-atherosclerosis effect by reinforcing AMBRA1-mediated endothelial autophagy.Eur. J. Pharmacol.202291617464110.1016/j.ejphar.2021.17464134800465
     [Google Scholar]
  11. YuJ. ZhaoX. YanX. LiW. LiuY. WangJ. WangJ. YangY. HaoY. LiangZ. TaoY. YuanY. DuZ. Aloe-emodin ameliorated MI-induced cardiac remodeling in mice via inhibiting TGF-β/SMAD signaling via up-regulating SMAD7.Phytomedicine202311415479310.1016/j.phymed.2023.15479337011420
     [Google Scholar]
  12. SuZ. HangP. HuJ. ZhengY. SunH. GuoJ. LiuK. DuZ. Aloe-emodin exerts cholesterol-lowering effects by inhibiting proprotein convertase subtilisin/kexin type 9 in hyperlipidemic rats.Acta Pharmacol. Sin.20204181085109210.1038/s41401‑020‑0392‑832203084
     [Google Scholar]
  13. ZhuM. HeQ. WangY. DuanL. RongK. WuY. DingY. MiY. GeX. YangX. YuY. Exploring the mechanism of aloe-emodin in the treatment of liver cancer through network pharmacology and cell experiments.Front. Pharmacol.202314123884110.3389/fphar.2023.123884137900162
     [Google Scholar]
  14. ZhaoY. ChenZ. CaiY. XueJ. ZhangL. WangL. ZhaoM. ZhengY. XiaT. YuH. JiangT. SunY. Aloe-emodin destroys the biofilm of Helicobacter pylori by targeting the outer membrane protein 6.Microbiol. Res.202427812753910.1016/j.micres.2023.12753937956613
     [Google Scholar]
  15. ParvezM.K. Al-DosariM.S. AlamP. RehmanM. AlajmiM.F. AlqahtaniA.S. The anti‐hepatitis B virus therapeutic potential of anthraquinones derived from Aloe vera.Phytother. Res.201933112960297010.1002/ptr.647131410907
     [Google Scholar]
  16. ChenY. FengB. YuanY. HuJ. ZhaoW. JiangH. LiW. FanZ. DuZ. Aloe emodin reduces cardiac inflammation induced by a high-fat diet through the TLR4 signaling pathway.Mediators Inflamm.2020202011210.1155/2020/631852032089647
     [Google Scholar]
  17. ZhaoJ. O’NeilM. SchonfeldM. KomatzA. WeinmanS.A. TikhanovichI. Hepatocellular protein arginine methyltransferase 1 suppresses alcohol‐induced hepatocellular carcinoma formation by inhibition of inducible nitric oxide synthase.Hepatol. Commun.20204679080810.1002/hep4.148832490317
     [Google Scholar]
  18. ThiebautC. EveL. PoulardC. RomancerL.M. Structure, activity, and function of PRMT1.Life20211111114710.3390/life1111114734833023
     [Google Scholar]
  19. ZhuQ. WangD. LiangF. TongX. LiangZ. WangX. ChenY. MoD. Protein arginine methyltransferase PRMT1 promotes adipogenesis by modulating transcription factors C/EBPβ and PPARγ.J. Biol. Chem.2022298910230910.1016/j.jbc.2022.10230935921899
     [Google Scholar]
  20. WangY. YanS. LiuX. DengF. WangP. YangL. HuL. HuangK. HeJ. PRMT4 promotes ferroptosis to aggravate doxorubicin-induced cardiomyopathy via inhibition of the Nrf2/GPX4 pathway.Cell Death Differ.202229101982199510.1038/s41418‑022‑00990‑535383293
     [Google Scholar]
  21. PyunJ.H. KimH.J. JeongM.H. AhnB.Y. VuongT.A. LeeD.I. ChoiS. KooS.H. ChoH. KangJ.S. Cardiac specific PRMT1 ablation causes heart failure through CaMKII dysregulation.Nat. Commun.201891510710.1038/s41467‑018‑07606‑y30504773
     [Google Scholar]
  22. NippertF. SchreckenbergR. SchlüterK.D. Isolation and cultivation of adult rat cardiomyocytes.J. Vis. Exp.20171285663410.3791/5663429155786
     [Google Scholar]
  23. ZhangY. JiaoL. SunL. LiY. GaoY. XuC. ShaoY. LiM. LiC. LuY. PanZ. XuanL. ZhangY. LiQ. YangR. ZhuangY. ZhangY. YangB. LncRNA ZFAS1 as a SERCA2a Inhibitor to Cause Intracellular Ca 2+ overload and contractile dysfunction in a mouse model of myocardial infarction.Circ. Res.2018122101354136810.1161/CIRCRESAHA.117.31211729475982
     [Google Scholar]
  24. LiuY. WangJ. ZhaoX. LiW. LiuY. LiX. ZhaoD. YuJ. JiH. ShaoB. LiZ. WangJ. YangY. HaoY. WuY. YuanY. DuZ. CDR1as promotes arrhythmias in myocardial infarction via targeting the NAMPT-NAD+ pathway.Biomed. Pharmacother.202316511526710.1016/j.biopha.2023.11526737542851
     [Google Scholar]
  25. ShuaiW. KongB. FuH. ShenC. HuangH. Loss of MD1 increases vulnerability to ventricular arrhythmia in diet-induced obesity mice via enhanced activation of the TLR4/MyD88/CaMKII signaling pathway.Nutr. Metab. Cardiovasc. Dis.201929999199810.1016/j.numecd.2019.06.00431353205
     [Google Scholar]
  26. SánchezM. González-BurgosE. IglesiasI. Gómez-SerranillosM.P. Pharmacological update properties of Aloe Vera and its major active constituents.Molecules2020256132410.3390/molecules2506132432183224
     [Google Scholar]
  27. HuB. ZhangH. MengX. WangF. WangP. Aloe-emodin from rhubarb (Rheum rhabarbarum) inhibits lipopolysaccharide-induced inflammatory responses in RAW264.7 macrophages.J. Ethnopharmacol.2014153384685310.1016/j.jep.2014.03.05924685589
     [Google Scholar]
  28. XuY. WanY. LiuF. ChenJ. TanT. GuoL. Simultaneous determination of seven anthraquinones in Cassiae semen by natural deep eutectic solvent extraction.Phytochem. Anal.20223381246125610.1002/pca.317636191586
     [Google Scholar]
  29. HeY. XiJ. FangJ. ZhangB. CaiW. Aloe-emodin alleviates doxorubicin-induced cardiotoxicity via inhibition of ferroptosis.Free Radic. Biol. Med.2023206132110.1016/j.freeradbiomed.2023.06.02537364691
     [Google Scholar]
  30. YuY. LiuH. YangD. HeF. YuanY. GuoJ. HuJ. YuJ. YanX. WangS. DuZ. Aloe-emodin attenuates myocardial infarction and apoptosis via up-regulating miR-133 expression.Pharmacol. Res.201914610431510.1016/j.phrs.2019.10431531207343
     [Google Scholar]
  31. WelshA. HammadM. PiñaI.L. KulinskiJ. Obesity and cardiovascular health.Eur. J. Prev. Cardiol.20243181026103510.1093/eurjpc/zwae02538243826
     [Google Scholar]
  32. PaleeS. MintaW. MantorD. SuthamW. KerdphooS. PratchayasakulW. ChattipakornS.C. ChattipakornN. Estrogen deprivation aggravates intracellular calcium dyshomeostasis in the heart of obese‐insulin resistant rats.J. Cell. Physiol.201923456983699110.1002/jcp.2744430417357
     [Google Scholar]
  33. GongY. LiG. TaoJ. WuN.N. KandadiM.R. BiY. WangS. PeiZ. RenJ. Double knockout of Akt2 and AMPK accentuates high fat diet-induced cardiac anomalies through a cGAS-STING-mediated mechanism.Biochim. Biophys. Acta Mol. Basis Dis.202018661016585510.1016/j.bbadis.2020.16585532512189
     [Google Scholar]
  34. GuoR. ZhangY. TurdiS. RenJ. Adiponectin knockout accentuates high fat diet-induced obesity and cardiac dysfunction: Role of autophagy.Biochim. Biophys. Acta Mol. Basis Dis.2013183281136114810.1016/j.bbadis.2013.03.01323524376
     [Google Scholar]
  35. Lima-LeopoldoA.P. LeopoldoA.S. SugizakiM.M. BrunoA. NascimentoA.F. LuvizottoR.A. JúniorO.S.A.Jr CastardeliE. PadovaniC.R. CicognaA.C. Myocardial dysfunction and abnormalities in intracellular calcium handling in obese rats.Arq. Bras. Cardiol.201197323224010.1590/S0066‑782X201100500006121584481
     [Google Scholar]
  36. LozanoW. CalvoC. Arias-MutisO. DíazA. Such-MiquelL. ZhaoJ. AlberolaA. ChorroF. ZarzosoM. Diet-induced metabolic syndrome reduced heart rate variability and increased irregularity and complexity of Short-Term RR time series in rabbits.Animals20199857210.3390/ani908057231426570
     [Google Scholar]
  37. ZarzosoM. MironovS. Guerrero-SernaG. WillisB.C. PanditS.V. Ventricular remodelling in rabbits with sustained high‐fat diet.Acta Physiol.20142111364710.1111/apha.1218524304486
     [Google Scholar]
  38. LiZ. HeQ. WuC. ChenL. BiF. ZhouY. ShanH. Apelin shorten QT interval by inhibiting Kir2.1/IK1 via a PI3K way in acute myocardial infarction.Biochem. Biophys. Res. Commun.2019517227227710.1016/j.bbrc.2019.07.04131349969
     [Google Scholar]
  39. WackerC. DamsN. SchauerA. RitzerA. VolkT. WagnerM. Region-specific mechanisms of corticosteroid-mediated inotropy in rat cardiomyocytes.Sci. Rep.20201011160410.1038/s41598‑020‑68308‑432665640
     [Google Scholar]
  40. TateishiH. YanoM. MochizukiM. SuetomiT. OnoM. XuX. UchinoumiH. OkudaS. OdaT. KobayashiS. YamamotoT. IkedaY. OhkusaT. IkemotoN. MatsuzakiM. Defective domain-domain interactions within the ryanodine receptor as a critical cause of diastolic Ca2+ leak in failing hearts.Cardiovasc. Res.200881353654510.1093/cvr/cvn30318996969
     [Google Scholar]
  41. PásekM. BébarováM. ŠimurdováM. ŠimurdaJ. Functional consequences of changes in the distribution of Ca2+ extrusion pathways between t-tubular and surface membranes in a model of human ventricular cardiomyocyte.J. Mol. Cell. Cardiol.202419311312410.1016/j.yjmcc.2024.06.01038960316
     [Google Scholar]
  42. LortonB.M. ShechterD. Cellular consequences of arginine methylation.Cell. Mol. Life Sci.201976152933295610.1007/s00018‑019‑03140‑231101937
     [Google Scholar]
  43. NingJ. ChenL. XiaoG. ZengY. ShiW. TanzhuG. ZhouR. The protein arginine methyltransferase family (PRMTs) regulates metastases in various tumors: From experimental study to clinical application.Biomed. Pharmacother.202316711545610.1016/j.biopha.2023.11545637696085
     [Google Scholar]
  44. SudhakarS.R.N. KhanS.N. ClarkA. Hendrickson-RebizantT. PatelS. LakowskiT.M. DavieJ.R. Protein arginine methyltransferase 1, a major regulator of biological processes.Biochem. Cell Biol.2024102210612610.1139/bcb‑2023‑021237922507
     [Google Scholar]
  45. KumarasamyC. SinghG. RamanP. MalaK. Effect of protein arginine methyltransferase-1 inhibition on hypoxia-induced vasoconstriction.Med. Hypotheses201585674074310.1016/j.mehy.2015.10.01826527496
     [Google Scholar]
  46. TanX. LiJ.K. SunJ.C. JiaoP.L. WangY.K. WuZ.T. LiuB. WangW.Z. The asymmetric dimethylarginine-mediated inhibition of nitric oxide in the rostral ventrolateral medulla contributes to regulation of blood pressure in hypertensive rats.Nitric Oxide201767586710.1016/j.niox.2017.04.00228392446
     [Google Scholar]
  47. KopalianiI. JarzebskaN. BilloffS. KolouschekA. Martens-LobenhofferJ. BornsteinS.R. Bode-BögerS.M. RagavanV.N. WeissN. MangoniA.A. DeussenA. RodionovR.N. Overexpression of dimethylarginine dimethylaminohydrolase 1 protects from angiotensin II-induced cardiac hypertrophy and vascular remodeling.Am. J. Physiol. Heart Circ. Physiol.20213215H825H83810.1152/ajpheart.00064.202134533401
     [Google Scholar]
  48. ChenX. NiroomandF. LiuZ. ZanklA. KatusH.A. JahnL. TiefenbacherC.P. Expression of nitric oxide related enzymes in coronary heart disease.Basic Res. Cardiol.2006101434635310.1007/s00395‑006‑0592‑516705470
     [Google Scholar]
  49. CaoN. ZhangF. YinJ. ZhangJ. BianX. ZhengG. LiN. LinY. LuoL. LPCAT2 inhibits colorectal cancer progression via the PRMT1/SLC7A11 axis.Oncogene202443221714172510.1038/s41388‑024‑02996‑438605214
     [Google Scholar]
  50. LuoL. WuX. FanJ. DongL. WangM. ZengY. LiS. YangW. JiangJ. WangK. FBXO7 ubiquitinates PRMT1 to suppress serine synthesis and tumor growth in hepatocellular carcinoma.Nat. Commun.2024151479010.1038/s41467‑024‑49087‑238839752
     [Google Scholar]
  51. YoshimatsuM. ToyokawaG. HayamiS. UnokiM. TsunodaT. FieldH.I. KellyJ.D. NealD.E. MaeharaY. PonderB.A.J. NakamuraY. HamamotoR. Dysregulation of PRMT1 and PRMT6, Type I arginine methyltransferases, is involved in various types of human cancers.Int. J. Cancer2011128356257310.1002/ijc.2536620473859
     [Google Scholar]
  52. GottschalkB. KoshenovZ. Waldeck-WeiermairM. RadulovićS. OflazF.E. HirtlM. BachkoenigO.A. LeitingerG. MalliR. GraierW.F. MICU1 controls spatial membrane potential gradients and guides Ca2+ fluxes within mitochondrial substructures.Commun. Biol.20225164910.1038/s42003‑022‑03606‑335778442
     [Google Scholar]
  53. KoshenovZ. OflazF.E. HirtlM. BachkoenigO.A. RostR. OsibowK. GottschalkB. Madreiter-SokolowskiC.T. Waldeck-WeiermairM. MalliR. GraierW.F. The contribution of uncoupling protein 2 to mitochondrial Ca2+ homeostasis in health and disease – A short revisit.Mitochondrion20205516417310.1016/j.mito.2020.10.00333069910
     [Google Scholar]
  54. ChenY.F. ZhangA.Y. ZouA.P. CampbellW.B. LiP.L. Protein methylation activates reconstituted ryanodine receptor-ca release channels from coronary artery myocytes.J. Vasc. Res.200441322924010.1159/00007817815118362
     [Google Scholar]
/content/journals/cmp/10.2174/0118761429364907250319054353
Loading
Aloe-Emodin Relieves Myocardial Intracellular Calcium Homeostasis Imbalance Induced by High-fat Diet via Protein Arginine Methyltransferase/ Ca2+/Calmodulin- Dependent Protein Kinase II Signaling Pathway in Rats
Curr Mol Pharmacol 17, e18761429364907 (2024); https://doi.org/10.2174/0118761429364907250319054353
/content/journals/cmp/10.2174/0118761429364907250319054353
/content/journals/cmp/10.2174/0118761429364907250319054353
Loading

Data & Media loading...

Supplements

Supplementary material is available on the Publisher’s website.

file format download Download

  • Article Type:     Research Article
Keyword(s): Aloe-emodin; Ca2+ handling; Cardiomyocytes; High-fat diet; Palmitic acid; Protein arginine methyltransferase 1

Most Cited Most Cited RSS feed

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