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

Abstract

Background:

Artemisinin (ART) is mainly derived from , a traditional Chinese medicinal plant, and has been found to affect cellular biochemical processes, such as proliferation, angiogenesis, and apoptosis, in addition to its antimalarial properties. However, its effect on cardiac hypertrophy and the underlying mechanisms remain unclear.

Objectives:

This study aimed to investigate the effect of ART on cardiac hypertrophy and explore its possible mechanisms.

Materials and Methods:

A rat model was established by intraperitoneal injection of isoproterenol (ISO) for 3 days, and the degree of myocardial hypertrophy was compared among 5 groups: a control (CON) group, an ISO group, and groups treated with different doses of ART (7 mg/kg/d, 35 mg/kg/d, and 75 mg/kg/d). Echocardiography was used to evaluate cardiac function and structure. The cross-sectional area of cardiomyocytes was measured by hematoxylin and eosin (H&E) staining. The heart weight (HW), body weight (BW), and tail length were measured, and the HW/tail length ratio and the HW/BW ratio were calculated. H9c2 rat cardiomyocytes were cultured, and different amounts of ART were added 2 hours before ISO stimulation. Phalloidin staining was used to evaluate the degree of cell hypertrophy. The levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) were quantified in rat plasma and cell supernatant using enzyme-linked immunosorbent assay (ELISA), while the expression levels of p-ERK1/2, p-JNK, and p-p38 MAPK were assessed in the myocardium and H9c2 cells via western blot analysis.

Results:

Intragastric administration of ART at a dosage of 35 mg/kg/d or over mitigated the early-stage cardiac hypertrophy induced by ISO in rats led to a reduction in left ventricular posterior wall diastolic thickness, interventricular septal thickness at diastole, lowered ANP and BNP levels, as well as a decrease in HW/tail length and HW/BW ratio. studies demonstrated that ART at a concentration of 100 μM inhibited ISO-mediated hypertrophy of H9c2 cells. The ISO group showed a higher p-ERK/GAPDH ratio and p-p38 MAPK/GAPDH ratio than the control group both and . Although the p-JNK/GAPDH ratio was increased in the ISO group, there was no statistical difference. The p-ERK/GAPDH and p-p38/GAPDH ratios were significantly lower in the ART group than in the ISO group.

Conclusion:

The mechanism of ART against cardiac hypertrophy was related to inhibition of the ERK1/2 and p38 MAPK signaling pathways.

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.
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2024-01-01
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References

  1. LiuR. MolkentinJ.D. Regulation of cardiac hypertrophy and remodeling through the dual-specificity MAPK phosphatases (DUSPs).J. Mol. Cell. Cardiol.2016101444910.1016/j.yjmcc.2016.08.01827575022
    [Google Scholar]
  2. KehatI. DavisJ. TiburcyM. AccorneroF. Saba-El-LeilM.K. MailletM. YorkA.J. LorenzJ.N. ZimmermannW.H. MelocheS. MolkentinJ.D. Extracellular signal-regulated kinases 1 and 2 regulate the balance between eccentric and concentric cardiac growth.Circ. Res.2011108217618310.1161/CIRCRESAHA.110.23151421127295
    [Google Scholar]
  3. ZhangB. ZhangP. TanY. FengP. ZhangZ. LiangH. DuanW. JinZ. WangX. LiuJ. GaoE. YuS. YiD. SunY. YiW. C1q-TNF-related protein-3 attenuates pressure overload-induced cardiac hypertrophy by suppressing the p38/CREB pathway and p38-induced ER stress.Cell Death Dis.201910752010.1038/s41419‑019‑1749‑031285424
    [Google Scholar]
  4. LiR.J. XuJ.J. ZhangZ.H. ChenM.W. LiuS.X. YangC. LiY.L. LuoP. LiuY.J. TangR. ShanZ.G. Rhein ameliorates transverse aortic constriction-induced cardiac hypertrophy via regulating STAT3 and p38 MAPK signaling pathways.Front. Pharmacol.20221394057410.3389/fphar.2022.94057436091816
    [Google Scholar]
  5. KojonazarovB. NovoyatlevaT. BoehmM. HappeC. SibinskaZ. TianX. SajjadA. LuitelH. KriechlingP. PosernG. EvansS.M. GrimmingerF. GhofraniH.A. WeissmannN. BogaardH.J. SeegerW. SchermulyR.T. p38 MAPK inhibition improves heart function in pressure-loaded right ventricular hypertrophy.Am. J. Respir. Cell Mol. Biol.201757560361410.1165/rcmb.2016‑0374OC28657795
    [Google Scholar]
  6. WangK.S. LiJ. WangZ. MiC. MaJ. PiaoL.X. XuG.H. LiX. JinX. Artemisinin inhibits inflammatory response via regulating NF-kappaB and MAPK signaling pathways.Immunopharmacol Immunotoxicol.2017391283610.1080/08923973.2016.1267744
    [Google Scholar]
  7. ZhangW. XiongL. ChenJ. TianZ. LiuJ. ChenF. RenM. GuanW. ZhangS. Artemisinin protects porcine mammary epithelial cells against lipopolysaccharide-induced inflammatory injury by regulating the NF-κB and MAPK signaling pathways.Animals2021116152810.3390/ani11061528
    [Google Scholar]
  8. LiH.X. LiuH. WangC.M. WangH.J. ChenJ. Artesunate restraining MAPK passage by smad7 to resist pulmonary fibrosis.Eur. Rev. Med. Pharmacol. Sci.201418213199320425487928
    [Google Scholar]
  9. LiW. MaG. DengY. WuQ. WangZ. ZhouQ. Artesunate exhibits synergistic anti-cancer effects with cisplatin on lung cancer A549 cells by inhibiting MAPK pathway.Gene202176614513410.1016/j.gene.2020.14513432898605
    [Google Scholar]
  10. BeccaficoS. MorozziG. MarchettiM.C. RiccardiC. SidoniA. DonatoR. SorciG. Artesunate induces ROS- and p38 MAPK-mediated apoptosis and counteracts tumor growth in vivo in embryonal rhabdomyosarcoma cells.Carcinogenesis20153691071108310.1093/carcin/bgv09826153023
    [Google Scholar]
  11. ZhangS. ShiL. MaH. LiH. LiY. LuY. WangQ. LiW. Dihydroartemisinin induces apoptosis in human gastric cancer cell line BGC-823 through activation of JNK1/2 and p38 MAPK signaling pathways.J. Recept. Signal Transduct. Res.201737217418010.1080/10799893.2016.120394227401020
    [Google Scholar]
  12. LuH. WangB. CuiN. ZhangY. Artesunate suppresses oxidative and inflammatory processes by activating Nrf2 and ROS‑dependent p38 MAPK and protects against cerebral ischemia‑reperfusion injury.Mol. Med. Rep.20181756639664610.3892/mmr.2018.866629512760
    [Google Scholar]
  13. PengT. LiS. LiuL. YangC. FarhanM. ChenL. SuQ. ZhengW. Artemisinin attenuated ischemic stroke induced cell apoptosis through activation of ERK1/2/CREB/BCL-2 signaling pathway in vitro and in vivo.Int. J. Biol. Sci.202218114578459410.7150/ijbs.6989235864966
    [Google Scholar]
  14. SalamonR.J. MahmoudA.I. Bridging the communication gap: Cardiomyocytes reciprocate sympathetic nerve signalling.J. Physiol.2022600122827282810.1113/JP28317335614020
    [Google Scholar]
  15. VidtD.G. BakstA.W. GrahamR.M. Adrenergic receptors: Structure and function.Cleve. Clin. J. Med.199057548149110.3949/ccjm.57.5.4812164898
    [Google Scholar]
  16. MasliukovP.M. MoiseevK. EmanuilovA.I. AnikinaT.A. ZverevA.A. NozdrachevA.D. Development of neuropeptide Y-mediated heart innervation in rats.Neuropeptides201655475410.1016/j.npep.2015.10.00726589184
    [Google Scholar]
  17. QiJ. TanY. FanD. PanW. YuJ. XuW. WuJ. ZhangM. Songling xuemaikang capsule inhibits isoproterenol-induced cardiac hypertrophy via CaMKIIδ and ERK1/2 pathways.J. Ethnopharmacol.202025311266010.1016/j.jep.2020.11266032061912
    [Google Scholar]
  18. HeX. YangS. DengJ. WuQ. ZangW.J. Amelioration of circadian disruption and calcium-handling protein defects by choline alleviates cardiac remodeling in abdominal aorta coarctation rats.Lab. Invest.2021101787889610.1038/s41374‑021‑00578‑633649466
    [Google Scholar]
  19. ChenM.Z. BuQ.T. PangS.C. LiF.L. SunM.N. ChuE.F. LiH. Tetrodotoxin attenuates isoproterenol-induced hypertrophy in H9c2 rat cardiac myocytes.Mol. Cell. Biochem.20123711-2778810.1007/s11010‑012‑1424‑622941212
    [Google Scholar]
  20. KumariS. KatareP.B. ElancheranR. NizamiH.L. ParameshaB. AravaS. SarmaP.P. KumarR. MahajanD. KumarY. DeviR. BanerjeeS.K. Musa balbisiana fruit rich in polyphenols attenuates isoproterenol-induced cardiac hypertrophy in rats via inhibition of inflammation and oxidative stress.Oxid. Med. Cell. Longev.2020202011410.1155/2020/714749832082481
    [Google Scholar]
  21. VelusamyP. MohanT. RaviD.B. Kishore KumarS.N. SrinivasanA. ChakrapaniL.N. SinghA. VaradharajS. KalaiselviP. Targeting the Nrf2/ARE signalling pathway to mitigate isoproterenol-induced cardiac hypertrophy: Plausible role of hesperetin in redox homeostasis.Oxid. Med. Cell. Longev.2020202011310.1155/2020/956827832952852
    [Google Scholar]
  22. MaoH. WangX. GaoY. ChangY. ChenL. NiuZ. AiJ. GaoX. Danhong injection attenuates isoproterenol-induced cardiac hypertrophy by regulating p38 and NF-κb pathway.J. Ethnopharmacol.2016186202910.1016/j.jep.2016.03.01526970569
    [Google Scholar]
  23. WangF. GaoQ. YangJ. WangC. CaoJ. SunJ. FanZ. FuL. Artemisinin suppresses myocardial ischemia–reperfusion injury via NLRP3 inflammasome mechanism.Mol. Cell. Biochem.20204741-217118010.1007/s11010‑020‑03842‑332729005
    [Google Scholar]
  24. GuY. WangX. WangX. YuanM. WuG. HuJ. TangY. HuangC. Artemisinin attenuates post-infarct myocardial remodeling by down-regulating the NF-κB pathway.Tohoku J. Exp. Med.2012227316117010.1620/tjem.227.16122729178
    [Google Scholar]
  25. ChoiK.C. AuerspergN. LeungP.C.K. Mitogen-activated protein kinases in normal and (pre)neoplastic ovarian surface epithelium.Reprod. Biol. Endocrinol.2003117110.1186/1477‑7827‑1‑7114577832
    [Google Scholar]
  26. ChunJ. JooE.J. KangM. KimY.S. Platycodin D induces anoikis and caspase‐mediated apoptosis via p38 MAPK in AGS human gastric cancer cells.J. Cell. Biochem.2013114245647010.1002/jcb.2438622961809
    [Google Scholar]
  27. LuM. WangY. ZhanX. The MAPK pathway-based drug therapeutic targets in pituitary adenomas.Front. Endocrinol.20191033010.3389/fendo.2019.0033031231308
    [Google Scholar]
  28. GuoZ. LiuF.Y. YangD. WangM.Y. LiC.F. TangN. MaS.Q. AnP. YangZ. TangQ.Z. Salidroside ameliorates pathological cardiac hypertrophy via TLR4‐TAK1 ‐dependent signaling.Phytother. Res.20233751839184910.1002/ptr.770136512326
    [Google Scholar]
  29. HuiX. HuF. LiuJ. LiC. YangY. ShuS. LiuP. WangF. LiS. FBXW5 acts as a negative regulator of pathological cardiac hypertrophy by decreasing the TAK1 signaling to pro-hypertrophic members of the MAPK signaling pathway.J. Mol. Cell. Cardiol.2021151314310.1016/j.yjmcc.2020.09.00832971071
    [Google Scholar]
  30. GanM. ZhangS. FanY. TanY. GuoZ. ChenL. BaiL. JiangD. HaoX. LiX. ShenL. ZhuL. The expression of microRNA in adult rat heart with isoproterenol-induced cardiac hypertrophy.Cells202095117310.3390/cells905117332397324
    [Google Scholar]
  31. SomvanshiR.K. QiuX. KumarU. Isoproterenol induced hypertrophy and associated signaling pathways are modulated by Somatostatin in H9c2 cells.Int. J. Cardiol.201316731012102210.1016/j.ijcard.2012.03.07722465343
    [Google Scholar]
  32. DennyW.A. Inhibitors and activators of the p38 mitogen-activated MAP kinase (MAPK) family as drugs to treat cancer and inflammation.Curr. Cancer Drug Targets202222320922010.2174/156800962266622021514283735168519
    [Google Scholar]
  33. JiangT. GongY. ZhangW. QiuJ. ZhengX. LiZ. YangG. HongZ. PD0325901, an ERK inhibitor, attenuates RANKL‐induced osteoclast formation and mitigates cartilage inflammation by inhibiting the NF-κB and MAPK pathways.Bioorg. Chem.202313210632110.1016/j.bioorg.2022.10632136642020
    [Google Scholar]
  34. MunckJ.M. BerdiniV. BevanL. BrothwoodJ.L. ASTX029, a Novel Dual-mechanism ERK Inhibitor, Modulates Both the Phosphorylation and Catalytic Activity of ERK.Molecular Cancer Therapeutics202120101757176810.1158/1535‑7163.MCT‑20‑090934330842
    [Google Scholar]
  35. NakagawaY. NishikimiT. KuwaharaK. Atrial and brain natriuretic peptides: Hormones secreted from the heart.Peptides2019111182510.1016/j.peptides.2018.05.01229859763
    [Google Scholar]
  36. GuptaD.K. WangT.J. Natriuretic peptides and cardiometabolic health.Circ. J.20157981647165510.1253/circj.CJ‑15‑058926103984
    [Google Scholar]
  37. LiX. LanY. WangY. NieM. LuY. ZhaoE. Telmisartan suppresses cardiac hypertrophy by inhibiting cardiomyocyte apoptosis via the NFAT/ANP/BNP signaling pathway.Mol. Med. Rep.20171552574258210.3892/mmr.2017.631828447738
    [Google Scholar]
  38. TsaiC.Y. KuoW.W. ShibuM.A. LinY.M. LiuC.N. ChenY.H. DayC.H. ShenC.Y. ViswanadhaV.P. HuangC.Y. E2/ER β inhibit ISO-induced cardiac cellular hypertrophy by suppressing Ca2+-calcineurin signaling.PLoS One2017129e018415310.1371/journal.pone.018415328863192
    [Google Scholar]
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