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image of Qishen Huoxue Granule Ameliorates LPS-induced Cardiomyocyte Injury by Suppressing Excessive Autophagy via MasR/PI3K-AKT-mTOR Pathway

Abstract

Introduction

Qishen Huoxue Granule (QHG), a classical Traditional Chinese Medicine prescription, can reduce septic cardiomyopathy in clinic. However, the mechanism of QHG remains unclear. This study aims to investigate the mechanism and effect of QHG-contained serum (QHG-CS) on sepsis-induced cardiomyopathy (SICM).

Methods

QHG was administered to Wistar rats via gavage to obtain QHG-CS. The chemical constituents of QHG-CS were identified via UPLC-Q-TOF-MS. In vitro, rat cardiomyocytes H9c2 cells isolated from embryonic BD1X rat heart tissue, and septic myocardial injury model was established by inducing H9c2 cells with lipopolysaccharide (LPS). Cell viability was assessed through CCK-8. Protein expression was determined using western blot, and gene expression was measured using real-time quantitative PCR. Cell autophagy was investigated by detecting LC3 expression using flow cytometry and immunofluorescence. In addition, three inhibitors, A779 (MasR), wortmannin (PI3K) and rapamycin (mTOR) were used to localize the potential therapeutic targets.

Results

QHG-CS significantly improved the survival of septic cardiomyocytes (p<0.0001). The expression of autophagy-related markers Beclin1, ATG5, and LC3II/I was increased in LPS-induced cardiomyocytes, which could be inhibited by QHG-CS. QHG-CS upregulated the mRNA expression of MasR, PI3K, and AKT, as well as the phosphorylation of PI3K, AKT, and mTOR. Moreover, A779 markedly lowered mRNA levels of MasR, PI3K, and mTOR, while wortmannin decreased mRNA levels of PI3K and mTOR, whereas rapamycin only suppressed mTOR phosphorylation.

Discussion

By inhibiting excessive autophagy through upregulation of the MasR/PI3K-AKT-mTOR pathway, QHG can alleviate sepsis-induced cardiomyocyte damage. This study provides novel perspectives for the management of sepsis-induced cardiac damage.

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2025-04-24
2025-09-05

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References

  1. Carbone F. Liberale L. Preda A. Schindler T.H. Montecucco F. Septic cardiomyopathy: From pathophysiology to the clinical setting. Cells 2022 11 18 2833 10.3390/cells11182833 36139408
    [Google Scholar]
  2. L’Heureux M. Sternberg M. Brath L. Turlington J. Kashiouris M.G. Sepsis-induced cardiomyopathy: A comprehensive review. Curr. Cardiol. Rep. 2020 22 5 35 10.1007/s11886‑020‑01277‑2 32377972
    [Google Scholar]
  3. Singer M. Deutschman C.S. Seymour C.W. Shankar-Hari M. Annane D. Bauer M. Bellomo R. Bernard G.R. Chiche J.D. Coopersmith C.M. Hotchkiss R.S. Levy M.M. Marshall J.C. Martin G.S. Opal S.M. Rubenfeld G.D. van der Poll T. Vincent J.L. Angus D.C. The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA 2016 315 8 801 810 10.1001/jama.2016.0287 26903338
    [Google Scholar]
  4. Martin L. Derwall M. Al Zoubi S. Zechendorf E. Reuter D.A. Thiemermann C. Schuerholz T. The septic heart. Chest 2019 155 2 427 437 10.1016/j.chest.2018.08.1037 30171861
    [Google Scholar]
  5. Wong Y.K. Cheung C.Y.Y. Tang C.S. Hai J.S.H. Lee C.H. Lau K.K. Au K.W. Cheung B.M.Y. Sham P.C. Xu A. Lam K.S.L. Tse H.F. High-sensitivity troponin I and B-type natriuretic peptide biomarkers for prediction of cardiovascular events in patients with coronary artery disease with and without diabetes mellitus. Cardiovasc. Diabetol. 2019 18 1 171 10.1186/s12933‑019‑0974‑2 31847896
    [Google Scholar]
  6. Liu Y.C. Yu M.M. Shou S.T. Chai Y.F. Sepsis-induced cardiomyopathy: Mechanisms and treatments. Front. Immunol. 2017 8 1021 10.3389/fimmu.2017.01021 28970829
    [Google Scholar]
  7. Lin Y.M. Lee M.C. Toh H.S. Chang W.T. Chen S.Y. Kuo F.H. Tang H.J. Hua Y.M. Wei D. Melgarejo J. Zhang Z.Y. Liao C.T. Association of sepsis-induced cardiomyopathy and mortality: A systematic review and meta-analysis. Ann. Intensive Care 2022 12 1 112 10.1186/s13613‑022‑01089‑3 36513882
    [Google Scholar]
  8. Li N. Zhou H. Wu H. Wu Q. Duan M. Deng W. Tang Q. STING-IRF3 contributes to lipopolysaccharide-induced cardiac dysfunction, inflammation, apoptosis and pyroptosis by activating NLRP3. Redox Biol. 2019 24 101215 10.1016/j.redox.2019.101215 31121492
    [Google Scholar]
  9. Lanspa M.J. Cirulis M.M. Wiley B.M. Olsen T.D. Wilson E.L. Beesley S.J. Brown S.M. Hirshberg E.L. Grissom C.K. Right ventricular dysfunction in early sepsis and septic shock. Chest 2021 159 3 1055 1063 10.1016/j.chest.2020.09.274 33068615
    [Google Scholar]
  10. Liu H. Xu C. Hu Q. Wang Y. Sepsis-induced cardiomyopathy: Understanding pathophysiology and clinical implications. Arch. Toxicol. 2025 99 2 467 480 10.1007/s00204‑024‑03916‑x 39601874
    [Google Scholar]
  11. Røsjø H. Varpula M. Hagve T.A. Karlsson S. Ruokonen E. Pettilä V. Omland T. Circulating high sensitivity troponin T in severe sepsis and septic shock: distribution, associated factors, and relation to outcome. Intensive Care Med. 2011 37 1 77 85 10.1007/s00134‑010‑2051‑x 20938765
    [Google Scholar]
  12. Salami O.M. Habimana O. Peng J. Yi G.H. Therapeutic strategies targeting mitochondrial dysfunction in sepsis-induced cardiomyopathy. Cardiovasc. Drugs Ther. 2024 38 1 163 180 10.1007/s10557‑022‑07354‑8 35704247
    [Google Scholar]
  13. Casper E. El Wakeel L. Sabri N. Khorshid R. Fahmy S.F. Melatonin: A potential protective multifaceted force for sepsis-induced cardiomyopathy. Life Sci. 2024 346 122611 10.1016/j.lfs.2024.122611 38580195
    [Google Scholar]
  14. Su Y. Zhang S. Ren A. Zhang L. Wang C. Observation of curative effect of traditional Chinese medicine Qishen Huoxue granule on severe sepsis. Chin. J. Integr. Trad. Western. Med. 2008 28 209 211 10.3321/j.issn:1003‑5370.2008.03.006 18476417
    [Google Scholar]
  15. Wang X. Li W. Zhang Y. Sun Q. Cao J. Tan N. Yang S. Lu L. Zhang Q. Wei P. Ma X. Wang W. Wang Y. Calycosin as a novel PI3K activator reduces inflammation and fibrosis in heart failure through AKT–IKK/STAT3 axis. Front. Pharmacol. 2022 13 828061 10.3389/fphar.2022.828061 35264961
    [Google Scholar]
  16. Zou L. Liu D. Yang H. Zhou C. Deng S. Xu N. He X. Liu Y. Shao M. Yu L. Liu J. Salvianolic acids from Salvia miltiorrhiza Bunge and their anti-inflammatory effects through the activation of α7nAchR signaling. J. Ethnopharmacol. 2023 317 116743 10.1016/j.jep.2023.116743 37331452
    [Google Scholar]
  17. Kim Y.J. Lee J.Y. Kim H.J. Kim D.H. Lee T.H. Kang M.S. Park W. Anti-Inflammatory effects of Angelica sinensis (Oliv.) diels water extract on RAW 264.7 induced with lipopolysaccharide. Nutrients 2018 10 5 647 10.3390/nu10050647 29883374
    [Google Scholar]
  18. Deng H. Yan C. Xiao T. Yuan D. Xu J. Total glucosides of Paeonia lactiflora pall inhibit vascular endothelial growth factor-induced angiogenesis. J. Ethnopharmacol. 2010 127 3 781 785 10.1016/j.jep.2009.09.053 19914370
    [Google Scholar]
  19. Zhu Y. Huang J. Chen X. Xie J. Yang Q. Wang J. Deng X. Senkyunolide I alleviates renal Ischemia-Reperfusion injury by inhibiting oxidative stress, endoplasmic reticulum stress and apoptosis. Int. Immunopharmacol. 2022 102 108393 10.1016/j.intimp.2021.108393 34857480
    [Google Scholar]
  20. Yu G. Luo Z. Zhou Y. Zhang L. Wu Y. Ding L. Shi Y. Uncovering the pharmacological mechanism of Carthamus tinctorius L. on cardiovascular disease by a systems pharmacology approach. Biomed. Pharmacother. 2019 117 109094 10.1016/j.biopha.2019.109094 31203131
    [Google Scholar]
  21. Zhen, Han Effect of Qishen Huoxue Granules in the treatment of sepsis with myocardial injury. J. Chin. Physician 2020 22 26 28 10.3760/cma.j.issn.1008‑1372.2020.01.007
    [Google Scholar]
  22. Wang G. Hao G. Xie M. Study of Qishen Huoxue Granules on myocardial protection in septic rats. Chin. J. Med. 2006 16 3404 3408 10.3969/j.issn.1005‑8982.2006.22.013
    [Google Scholar]
  23. Su Y.L. Wang H. Zhang S.W. Effect of Qishen Huoxue Granule in treating severe sepsis. Chung Kuo Chung Hsi I Chieh Ho Tsa Chih 2008 28 3 209 211 18476417
    [Google Scholar]
  24. Aman Y. Schmauck-Medina T. Hansen M. Morimoto R.I. Simon A.K. Bjedov I. Palikaras K. Simonsen A. Johansen T. Tavernarakis N. Rubinsztein D.C. Partridge L. Kroemer G. Labbadia J. Fang E.F. Autophagy in healthy aging and disease. Nature Aging 2021 1 8 634 650 10.1038/s43587‑021‑00098‑4 34901876
    [Google Scholar]
  25. Zheng M. Lou J. Fan Y. Fu C. Mao X. Li X. Zhong K. Lu L. Wang L. Chen Y. Zheng L. Identification of autophagy-associated circRNAs in sepsis-induced cardiomyopathy of mice. Sci. Rep. 2023 13 1 11807 10.1038/s41598‑023‑38998‑7 37479790
    [Google Scholar]
  26. Kuroshima T. Kawaguchi S. Okada M. Current perspectives of mitochondria in sepsis-induced cardiomyopathy. Int. J. Mol. Sci. 2024 25 9 4710 10.3390/ijms25094710 38731929
    [Google Scholar]
  27. Liu S. Yao S. Yang H. Liu S. Wang Y. Autophagy: Regulator of cell death. Cell Death Dis. 2023 14 10 648 10.1038/s41419‑023‑06154‑8 37794028
    [Google Scholar]
  28. Kim Y.C. Guan K.L. mTOR: a pharmacologic target for autophagy regulation. J. Clin. Invest. 2015 125 1 25 32 10.1172/JCI73939 25654547
    [Google Scholar]
  29. Gao Y. Zhang Y. Fan Y. Eupafolin ameliorates lipopolysaccharide-induced cardiomyocyte autophagy via PI3K/AKT/mTOR signaling pathway. Iran. J. Basic Med. Sci. 2019 22 11 1340 1346 10.22038/ijbms.2019.37748.8977 32128100
    [Google Scholar]
  30. Tang H. Wang G. Qishen Huoxue granules containing serum can improve the damage of septic cardiomyocytes by inhibiting excessive autophagy. Chin. Med. J. (Engl.) 2021 23 1466 1471
    [Google Scholar]
  31. Wu J. Lu A.D. Zhang L.P. Zuo Y.X. Jia Y.P. Study of clinical outcome and prognosis in pediatric core binding factor-acute myeloid leukemia. Chin. J. Hematol 2019 40 1 52 57 10.3760/cma.j.issn.0253‑2727.2019.01.010 30704229
    [Google Scholar]
  32. Pei H. Wang W. Zhao D. Su H. Su G. Zhao Z. G protein-coupled estrogen receptor 1 inhibits angiotensin II-induced cardiomyocyte hypertrophy via the regulation of PI3K-Akt-mTOR signalling and autophagy. Int. J. Biol. Sci. 2019 15 1 81 92 10.7150/ijbs.28304 30662349
    [Google Scholar]
  33. Hollenberg S.M. Singer M. Pathophysiology of sepsis-induced cardiomyopathy. Nat. Rev. Cardiol. 2021 18 6 424 434 10.1038/s41569‑020‑00492‑2 33473203
    [Google Scholar]
  34. Ajoolabady A. Chiong M. Lavandero S. Klionsky D.J. Ren J. Mitophagy in cardiovascular diseases: Molecular mechanisms, pathogenesis, and treatment. Trends Mol. Med. 2022 28 10 836 849 10.1016/j.molmed.2022.06.007 35879138
    [Google Scholar]
  35. Klionsky D.J. Petroni G. Amaravadi R.K. Baehrecke E.H. Ballabio A. Boya P. Bravo-San Pedro J.M. Cadwell K. Cecconi F. Choi A.M.K. Choi M.E. Chu C.T. Codogno P. Colombo M.I. Cuervo A.M. Deretic V. Dikic I. Elazar Z. Eskelinen E.L. Fimia G.M. Gewirtz D.A. Green D.R. Hansen M. Jäättelä M. Johansen T. Juhász G. Karantza V. Kraft C. Kroemer G. Ktistakis N.T. Kumar S. Lopez-Otin C. Macleod K.F. Madeo F. Martinez J. Meléndez A. Mizushima N. Münz C. Penninger J.M. Perera R.M. Piacentini M. Reggiori F. Rubinsztein D.C. Ryan K.M. Sadoshima J. Santambrogio L. Scorrano L. Simon H.U. Simon A.K. Simonsen A. Stolz A. Tavernarakis N. Tooze S.A. Yoshimori T. Yuan J. Yue Z. Zhong Q. Galluzzi L. Pietrocola F. Autophagy in major human diseases. EMBO J. 2021 40 19 e108863 10.15252/embj.2021108863 34459017
    [Google Scholar]
  36. Yin X. Xin H. Mao S. Wu G. Guo L. The role of autophagy in sepsis: Protection and injury to organs. Front. Physiol. 2019 10 1071 10.3389/fphys.2019.01071 31507440
    [Google Scholar]
  37. Taskin S. A new perspective on the adaptation and proliferation mechanism of cancer cells: Atypical kinase eEF-2K. Int. J. Curr. Med. Biol. Sci. 2022 2 143 149 10.5281/zenodo.6555602
    [Google Scholar]
  38. Cai Z.L. Shen B. Yuan Y. Liu C. Xie Q.W. Hu T.T. Yao Q. Wu Q.Q. Tang Q.Z. The effect of HMGA1 in LPS-induced myocardial inflammation. Int. J. Biol. Sci. 2020 16 11 1798 1810 10.7150/ijbs.39947 32398950
    [Google Scholar]
  39. Lei S. Zhang Y. Su W. Zhou L. Xu J. Xia Z. Remifentanil attenuates lipopolysaccharide-induced oxidative injury by downregulating PKCβ2 activation and inhibiting autophagy in H9C2 cardiomyocytes. Life Sci. 2018 213 109 115 10.1016/j.lfs.2018.10.041 30352239
    [Google Scholar]
  40. Rabie M.A. Abd El Fattah M.A. Nassar N.N. El-Abhar H.S. Abdallah D.M. Angiotensin 1-7 ameliorates 6-hydroxydopamine lesions in hemiparkinsonian rats through activation of MAS receptor/PI3K/Akt/BDNF pathway and inhibition of angiotensin II type-1 receptor/NF-κB axis. Biochem. Pharmacol. 2018 151 126 134 10.1016/j.bcp.2018.01.047 29428223
    [Google Scholar]
  41. Qin G.W. Lu P. Peng L. Jiang W. Ginsenoside Rb1 inhibits cardiomyocyte autophagy via PI3K/Akt/mTOR signaling pathway and reduces myocardial ischemia/reperfusion injury. Am. J. Chin. Med. 2021 49 8 1913 1927 10.1142/S0192415X21500907 34775933
    [Google Scholar]
  42. Ba L. Gao J. Chen Y. Qi H. Dong C. Pan H. Zhang Q. Shi P. Song C. Guan X. Cao Y. Sun H. Allicin attenuates pathological cardiac hypertrophy by inhibiting autophagy via activation of PI3K/Akt/mTOR and MAPK/ERK/mTOR signaling pathways. Phytomedicine 2019 58 152765 10.1016/j.phymed.2018.11.025 31005720
    [Google Scholar]
  43. Kishore R. Krishnamurthy P. Garikipati V.N.S. Benedict C. Nickoloff E. Khan M. Johnson J. Gumpert A.M. Koch W.J. Verma S.K. Interleukin-10 inhibits chronic angiotensin II-induced pathological autophagy. J. Mol. Cell. Cardiol 2015 89 Pt B 203 213 10.1016/j.yjmcc.2015.11.004 26549357
    [Google Scholar]
  44. Geng H. Zhang H. Cheng L. Dong S. Sivelestat ameliorates sepsis-induced myocardial dysfunction by activating the PI3K/AKT/mTOR signaling pathway. Int. Immunopharmacol. 2024 128 111466 10.1016/j.intimp.2023.111466 38176345
    [Google Scholar]
  45. Weng Y.S. Wang H.F. Pai P.Y. Jong G.P. Lai C.H. Chung L.C. Hsieh D.J.Y. HsuanDay, C.; Kuo, W.W.; Huang, C.Y. Tanshinone IIA prevents Leu27IGF-II-Induced cardiomyocyte hypertrophy mediated by estrogen receptor and subsequent Akt activation. Am. J. Chin. Med. 2015 43 8 1567 1591 10.1142/S0192415X15500895 26621443
    [Google Scholar]
  46. Zhao P. Wang Y. Zeng S. Lu J. Jiang T.M. Li Y.M. Protective effect of astragaloside IV on lipopolysaccharide-induced cardiac dysfunction via downregulation of inflammatory signaling in mice. Immunopharmacol. Immunotoxicol. 2015 37 5 428 433 10.3109/08923973.2015.1080266 26376109
    [Google Scholar]
  47. Liu B. Zhao H. Wang Y. Zhang H. Ma Y. Astragaloside I.V. Astragaloside IV attenuates ophagy. Pharmacology 2020 105 1-2 90 101 10.1159/000502865 31554002
    [Google Scholar]
  48. Zhou W. Chen Y. Zhang X. Astragaloside I.V. Astragaloside IV alleviates lipopolysaccharide-induced acute kidney injury through down-regulating cytokines, CCR5 and p-ERK, and elevating anti-oxidative ability. Med. Sci. Monit. 2017 23 1413 1420 10.12659/MSM.899618 28328867
    [Google Scholar]
  49. Xie S. Yang T. Wang Z. Li M. Ding L. Hu X. Geng L. Astragaloside IV attenuates sepsis-induced intestinal barrier dysfunction via suppressing RhoA/NLRP3 inflammasome signaling. Int. Immunopharmacol. 2020 78 106066 10.1016/j.intimp.2019.106066 31835087
    [Google Scholar]
  50. Li F. Lang F. Zhang H. Xu L. Wang Y. Zhai C. Hao E. Apigenin alleviates endotoxin‐induced myocardial toxicity by modulating inflammation, oxidative stress, and autophagy. Oxid. Med. Cell. Longev. 2017 2017 1 2302896 10.1155/2017/2302896 28828145
    [Google Scholar]
  51. Li X. Liu J. Wang J. Zhang D. Luteolin suppresses lipopolysaccharide induced cardiomyocyte hypertrophy and autophagy in vitro. Mol. Med. Rep. 2019 19 3 1551 1560 10.3892/mmr.2019.9803 30628693
    [Google Scholar]
  52. Vukovic D. Winkelvoß D. Kapp J.N. Hänny A.C. Bürgisser H. Riermeier L. Udovcic A. Tiefenboeck P. Plückthun A. Protein degradation kinetics measured by microinjection and live-cell fluorescence microscopy. Sci. Rep. 2024 14 1 27153 10.1038/s41598‑024‑76224‑0 39511251
    [Google Scholar]
  53. Fournier M.L. Paulson A. Pavelka N. Mosley A.L. Gaudenz K. Bradford W.D. Glynn E. Li H. Sardiu M.E. Fleharty B. Seidel C. Florens L. Washburn M.P. Delayed correlation of mRNA and protein expression in rapamycin-treated cells and a role for Ggc1 in cellular sensitivity to rapamycin. Mol. Cell. Proteomics 2010 9 2 271 284 10.1074/mcp.M900415‑MCP200 19955083
    [Google Scholar]
  54. Lee J.M. Hammarén H.M. Savitski M.M. Baek S.H. Control of protein stability by post-translational modifications. Nat. Commun. 2023 14 1 201 10.1038/s41467‑023‑35795‑8 36639369
    [Google Scholar]
  55. Wu C. Ba Q. Lu D. Li W. Salovska B. Hou P. Mueller T. Rosenberger G. Gao E. Di Y. Zhou H. Fornasiero E.F. Liu Y. Global and site-specific effect of phosphorylation on protein turnover. Dev. Cell 2021 56 1 111 124.e6 10.1016/j.devcel.2020.10.025 33238149
    [Google Scholar]
  56. Ko P.J. Dixon S.J. Protein palmitoylation and cancer. EMBO Rep. 2018 19 10 e46666 10.15252/embr.201846666 30232163
    [Google Scholar]
  57. Sirek T. Król-Jatręga K. Borawski P. Zmarzły N. Boroń D. Ossowski P. Nowotny-Czupryna O. Boroń K. Janiszewska-Bil D. Mitka-Krysiak E. Grabarek B.O. Distinct mRNA expression profiles and miRNA regulators of the PI3K/AKT/mTOR pathway in breast cancer: insights into tumor progression and therapeutic targets. Front. Oncol. 2025 14 1515387 10.3389/fonc.2024.1515387 39850811
    [Google Scholar]
  58. Akbarzadeh M. Mihanfar A. Akbarzadeh S. Yousefi B. Majidinia M. Crosstalk between miRNA and PI3K/AKT/mTOR signaling pathway in cancer. Life Sci. 2021 285 119984 10.1016/j.lfs.2021.119984 34592229
    [Google Scholar]
  59. Ashadul Sk M. K, H.; Matada, G.S.P.; Pal, R.; B v, M.; Mounika, S.; e, H.; M P, V.; D, A. Current developments in PI3K-based anticancer agents: Designing strategies, biological activity, selectivity, structure-activity correlation, and docking insight. Bioorg. Chem. 2025 154 108011 10.1016/j.bioorg.2024.108011 39662340
    [Google Scholar]
  60. Fan Q.W. Knight Z.A. Goldenberg D.D. Yu W. Mostov K.E. Stokoe D. Shokat K.M. Weiss W.A. A dual PI3 kinase/mTOR inhibitor reveals emergent efficacy in glioma. Cancer Cell 2006 9 5 341 349 10.1016/j.ccr.2006.03.029 16697955
    [Google Scholar]
  61. Coughlin C.A. Chahar D. Lekakis M. Youssfi A.A. Li L. Roberts E. Gallego N.C. Volmar C.H. Landgren O. Brothers S. Griswold A.J. Amador C. Bilbao D. Maura F. Schatz J.H. Bruton’s tyrosine kinase inhibition re-sensitizes multidrug-resistant DLBCL tumors driven by BCL10 gain-of-function mutants to venetoclax. Blood Cancer J. 2025 15 1 9 10.1038/s41408‑025‑01214‑y 39894894
    [Google Scholar]
  62. Mugume Y. Kazibwe Z. Bassham D.C. Target of Rapamycin in control of autophagy: Puppet master and signal integrator. Int. J. Mol. Sci. 2020 21 21 8259 10.3390/ijms21218259 33158137
    [Google Scholar]
  63. Shang X. Lin K. Yu R. Zhu P. Zhang Y. Wang L. Xu J. Chen K. Resveratrol protects the Myocardium in Sepsis by Activating the Phosphatidylinositol 3-Kinases (PI3K)/AKT/mammalian target of Rapamycin (mTOR) pathway and inhibiting the nuclear factor-κB (NF-κB) signaling pathway. Med. Sci. Monit. 2019 25 9290 9298 10.12659/MSM.918369 31806860
    [Google Scholar]
  64. Wu J. Sun C. Wang R. Li J. Zhou M. Yan M. Xue X. Wang C. Cardioprotective effect of paeonol against epirubicin-induced heart injury via regulating miR-1 and PI3K/AKT pathway. Chem. Biol. Interact. 2018 286 17 25 10.1016/j.cbi.2018.02.035 29505745
    [Google Scholar]
  65. Zeng J. Zhao H. Chen B. DJ-1/PARK7 inhibits high glucose-induced oxidative stress to prevent retinal pericyte apoptosis via the PI3K/AKT/mTOR signaling pathway. Exp. Eye Res. 2019 189 107830 10.1016/j.exer.2019.107830 31593688
    [Google Scholar]
  66. Yuan Z. Yang M. Liang Z. Yang C. Kong X. Wu Y. Wang S. Fan H. Ning C. Xiao W. Sun Z. Wu J. PI3K/AKT/mTOR, NF-κB and ERS pathway participated in the attenuation of H2O2-induced IPEC-J2 cell injury by koumine. J. Ethnopharmacol. 2023 304 116028 10.1016/j.jep.2022.116028 36529250
    [Google Scholar]
  67. Anilkumar S. A.; Dutta, S.; Aboo, S.; Ismail, A. Vitamin D as a modulator of molecular pathways involved in CVDs: Evidence from preclinical studies. Life Sci. 2024 357 123062 10.1016/j.lfs.2024.123062 39288869
    [Google Scholar]
  68. Hassanein E.H.M. Abd El-Ghafar O.A.M. Ahmed M.A. Sayed A.M. Gad-Elrab W.M. Ajarem J.S. Allam A.A. Mahmoud A.M. Edaravone and acetovanillone upregulate Nrf2 and PI3K/Akt/mTOR signaling and prevent cyclophosphamide cardiotoxicity in rats. Drug Des. Devel. Ther. 2020 14 5275 5288 10.2147/DDDT.S281854 33299300
    [Google Scholar]
  69. Younis N.S. Abduldaium M.S. Mohamed M.E. Protective effect of geraniol on oxidative, inflammatory and apoptotic alterations in isoproterenol-induced cardiotoxicity: Role of the Keap1/Nrf2/HO-1 and PI3K/Akt/mTOR pathways. Antioxidants 2020 9 10 977 10.3390/antiox9100977 33053761
    [Google Scholar]
  70. Xie X. Wang F. Ge W. Meng X. Fan L. Zhang W. Wang Z. Ding M. Gu S. Xing X. Sun X. Scutellarin attenuates oxidative stress and neuroinflammation in cerebral ischemia/reperfusion injury through PI3K/Akt-mediated Nrf2 signaling pathways. Eur. J. Pharmacol. 2023 957 175979 10.1016/j.ejphar.2023.175979 37611841
    [Google Scholar]
  71. Kong J. Kui H. Tian Y. Kong X. He T. Li Q. Gu C. Guo J. Liu C. Nephrotoxicity assessment of podophyllotoxin-induced rats by regulating PI3K/Akt/mTOR-Nrf2/HO1 pathway in view of toxicological evidence chain (TEC) concept. Ecotoxicol. Environ. Saf. 2023 264 115392 10.1016/j.ecoenv.2023.115392 37651795
    [Google Scholar]
  72. Liu B. Deng X. Jiang Q. Li G. Zhang J. Zhang N. Xin S. Xu K. Scoparone improves hepatic inflammation and autophagy in mice with nonalcoholic steatohepatitis by regulating the ROS/P38/Nrf2 axis and PI3K/AKT/mTOR pathway in macrophages. Biomed. Pharmacother. 2020 125 109895 10.1016/j.biopha.2020.109895 32000066
    [Google Scholar]
  73. Dewanjee S. Vallamkondu J. Kalra R.S. John A. Reddy P.H. Kandimalla R. Autophagy in the diabetic heart: A potential pharmacotherapeutic target in diabetic cardiomyopathy. Ageing Res. Rev. 2021 68 101338 10.1016/j.arr.2021.101338 33838320
    [Google Scholar]
  74. Popov S.V. Mukhomedzyanov A.V. Voronkov N.S. Derkachev I.A. Boshchenko A.A. Fu F. Sufianova G.Z. Khlestkina M.S. Maslov L.N. Regulation of autophagy of the heart in ischemia and reperfusion. Apoptosis 2023 28 1-2 55 80 10.1007/s10495‑022‑01786‑1 36369366
    [Google Scholar]
  75. Deng H. Chen Y. Wang L. Zhang Y. Hang Q. Li P. Zhang P. Ji J. Song H. Chen M. Jin Y. PI3K/mTOR inhibitors promote G6PD autophagic degradation and exacerbate oxidative stress damage to radiosensitize small cell lung cancer. Cell Death Dis. 2023 14 10 652 10.1038/s41419‑023‑06171‑7 37802999
    [Google Scholar]
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Qishen Huoxue Granule Ameliorates LPS-induced Cardiomyocyte Injury by Suppressing Excessive Autophagy via MasR/PI3K-AKT-mTOR Pathway
Bentham Science Publishers ; https://doi.org/10.2174/0113862073359792250401180222
/content/journals/cchts/10.2174/0113862073359792250401180222
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  • Article Type:     Research Article
Keywords: qishen huoxue granule ; cardiomyocyte injury ; MasR/PI3K-AKT-mTOR pathway ; Sepsis ; excessive autophagy

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