Skip to content
2000
image of Network Pharmacology Analysis and Experimental Validation Reveal the Mechanism of Action of Longlutong Decoction in the Treatment of

Abstract

Introduction

Longlutong Decoction (LLTD) is a Chinese traditional prescription used for coronary heart disease (CHD). The present study aimed to illuminate the mechanisms of LLTD treatment on CHD.

Methods

The therapeutic effect of LLTD on CHD was investigated using a CHD rat model. The chemical components of LLTD were identified, following which network pharmacology approaches were utilized to identify active components and disease-related targets. GO and KEGG analyses were conducted to explore potential molecular mechanisms. Finally, the molecular mechanism of LLTD treatment of CHD was verified.

Results

Histopathological assessment revealed markedly attenuated myocardial injury severity in the medicated groups when compared to the model group. Moreover, 81 potential active ingredients were identified in LLTD, with 645 overlapping targets between component targets and disease targets. Network analysis identified Pinocembrin, Magnoflorine, Jatrorrhizine as key active ingredients, and AKT1, TNF, IL-6, STAT3, and Bcl-2 as primary core targets. A total of 1792 biological processes were affected according to GO analysis, and 187 pathways were identified through KEGG analysis. Finally, molecular docking and experimental results validated that LLTD could alleviate cardiomyocyte injury in CHD by regulating the primary core targets.

Discussion

This study indicates that LLTD may achieve systematic modulating of the signaling network through a “network pharmacology” model, which provides valuable insights for the development of multi-target therapies targeting the complex pathological mechanism underlying CHD.

Conclusion

LLTD may exert cardioprotective effects by regulating inflammatory responses, apoptosis, and oxidative stress.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cchts/10.2174/0113862073426600251020060402
2025-11-14
2025-11-29

  • From This Site

    /content/journals/cchts/10.2174/0113862073426600251020060402
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. Timmis A. Townsend N. Gale C.P. Torbica A. Lettino M. Petersen S.E. Mossialos E.A. Maggioni A.P. Kazakiewicz D. May H.T. De Smedt D. Flather M. Zuhlke L. Beltrame J.F. Huculeci R. Tavazzi L. Hindricks G. Bax J. Casadei B. Achenbach S. Wright L. Vardas P. Mimoza L. Artan G. Aurel D. Chettibi M. Hammoudi N. Sisakian H. Pepoyan S. Metzler B. Siostrzonek P. Weidinger F. Jahangirov T. Aliyev F. Rustamova Y. Manak N. Mrochak A. Lancellotti P. Pasquet A. Claeys M. Kušljugić Z. Dizdarević Hudić L. Smajić E. Tokmakova M.P. Gatzov P.M. Milicic D. Bergovec M. Christou C. Moustra H.H. Christodoulides T. Linhart A. Taborsky M. Hansen H.S. Holmvang L. Kristensen S.D. Abdelhamid M. Shokry K. Kampus P. Viigimaa M. Ryödi E. Niemelä M. Rissanen T.T. Le Heuzey J-Y. Gilard M. Aladashvili A. Gamkrelidze A. Kereselidze M. Zeiher A. Katus H. Bestehorn K. Tsioufis C. Goudevenos J. Csanádi Z. Becker D. Tóth K. Jóna Hrafnkelsdóttir Þ. Crowley J. Kearney P. Dalton B. Zahger D. Wolak A. Gabrielli D. Indolfi C. Urbinati S. Imantayeva G. Berkinbayev S. Bajraktari G. Ahmeti A. Berisha G. Erkin M. Saamay A. Erglis A. Bajare I. Jegere S. Mohammed M. Sarkis A. Saadeh G. Zvirblyte R. Sakalyte G. Slapikas R. Ellafi K. El Ghamari F. Banu C. Beissel J. Felice T. Buttigieg S.C. Xuereb R.G. Popovici M. Boskovic A. Rabrenovic M. Ztot S. Abir-Khalil S. van Rossum A.C. Mulder B.J.M. Elsendoorn M.W. Srbinovska-Kostovska E. Kostov J. Marjan B. Steigen T. Mjølstad O.C. Ponikowski P. Witkowski A. Jankowski P. Gil V.M. Mimoso J. Baptista S. Vinereanu D. Chioncel O. Popescu B.A. Shlyakhto E. Oganov R. Foscoli M. Zavatta M. Dikic A.D. Beleslin B. Radovanovic M.R. Hlivák P. Hatala R. Kaliská G. Kenda M. Fras Z. Anguita M. Cequier Á. Muñiz J. James S. Johansson B. Platonov P. Zellweger M.J. Pedrazzini G.B. Carballo D. Shebli H.E. Kabbani S. Abid L. Addad F. Bozkurt E. Kayıkçıoğlu M. Erol M.K. Kovalenko V. Nesukay E. Wragg A. Ludman P. Ray S. Kurbanov R. Boateng D. Daval G. de Benito Rubio V. Sebastiao D. de Courtelary P.T. Bardinet I. European society of cardiology: Cardiovascular disease statistics 2019. Eur. Heart J. 2020 41 1 12 85 10.1093/eurheartj/ehz859 31820000
    [Google Scholar]
  2. Global health estimates: Global health estimates: Leading causes of death, 2000-2021 2025 Available from: https://www.who.int/data/gho/data/themes/mortality-and-global-health-estimates/ghe-leading-causes-of-death
  3. de Winter R.W. Walsh S.J. Hanratty C.G. Spratt J.C. Sprengers R.W. Twisk J.W.R. Vegting I. Schumacher S.P. Bom M.J. Hoek R. Verouden N.J. Delewi R. Nap A. Knaapen P. Percutaneous coronary intervention of native coronary artery versus saphenous vein graft in patients with prior coronary artery bypass graft surgery: Rationale and design of the multicenter, randomized PROCTOR trial. Am. Heart J. 2023 257 20 29 10.1016/j.ahj.2022.11.014 36410442
    [Google Scholar]
  4. Stähli B.E. Varbella F. Linke A. Schwarz B. Felix S.B. Seiffert M. Kesterke R. Nordbeck P. Witzenbichler B. Lang I.M. Kessler M. Valina C. Dibra A. Rohla M. Moccetti M. Vercellino M. Gaede L. Bott-Flügel L. Jakob P. Stehli J. Candreva A. Templin C. Schindler M. Wischnewsky M. Zanda G. Quadri G. Mangner N. Toma A. Magnani G. Clemmensen P. Lüscher T.F. Münzel T. Schulze P.C. Laugwitz K.L. Rottbauer W. Huber K. Neumann F.J. Schneider S. Weidinger F. Achenbach S. Richardt G. Kastrati A. Ford I. Maier W. Ruschitzka F. Timing of Complete revascularization with multivessel PCI for myocardial infarction. N. Engl. J. Med. 2023 389 15 1368 1379 10.1056/NEJMoa2307823 37634190
    [Google Scholar]
  5. Vallejo-Vaz A.J. Dharmayat K.I. Nzeakor N. Carrasco C.P. Fatoba S.T. Fonseca M.J. Tolani E. Lee C. Ray K.K. Recurrent cardiovascular and limb events in 294,428 patients with coronary or peripheral artery disease or ischemic stroke on antiplatelet monotherapy: The RESRISK cohort study. Atherosclerosis 2024 398 118589 10.1016/j.atherosclerosis.2024.118589 39277962
    [Google Scholar]
  6. Kupnovytska I.H. Romanyshyn N.M. Fitkovska I.P. Gubina N.V. Krasnopolsky S.Z. Klymenko V.I. Kalugina S.M. Effect of ivabradine on structural and functional changes of myocardium and NT-proBNP levels in patients with stable coronary heart disease after coronary stenting. Wiad. Lek. 2024 77 4 800 810 10.36740/WLek202404128 38865640
    [Google Scholar]
  7. Yang Y. Su C. Zhang X.Z. Li J. Huang S.C. Kuang H.F. Zhang Q.Y. Mechanisms of Xuefu Zhuyu Decoction in the treatment of coronary heart disease based on integrated metabolomics and network pharmacology approach. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 2023 1223 123712 10.1016/j.jchromb.2023.123712 37060624
    [Google Scholar]
  8. Li R. Han X. Wang Q. Wang C. Jing W. Zhang H. Wang J. Pan W. Network pharmacology analysis and clinical efficacy of the traditional Chinese medicine Bu-Shen-Jian-Pi. Part 3: Alleviation of hypoxia, muscle-wasting, and modulation of redox functions in amyotrophic lateral sclerosis]. Int. J. Clin. Pharmacol. Ther. 2024 62 4 169 177 10.5414/CP204520 38431830
    [Google Scholar]
  9. Zhang Z. Wu C. Liu N. Wang Z. Pan Z. Jiang Y. Tian J. Sun M. Modified Banxiaxiexin decoction benefitted chemotherapy in treating gastric cancer by regulating multiple targets and pathways. J. Ethnopharmacol. 2024 331 118277 10.1016/j.jep.2024.118277 38697407
    [Google Scholar]
  10. Chen Y. Ma S. Huo J. Ding S. Liu Q. Li C. Yao Y. Shang Y. Network pharmacology and bioinformatics of flavonoids from Scutellaria baicalensis stems: Mitigating Aβ-induced cognitive impairment in rats via the MEK-ERK-CREB pathway. Curr. Mol. Pharmacol. 2025 17 e18761429381010 10.2174/0118761429381010250512060455 40396317
    [Google Scholar]
  11. Liu Z. Zhang J. Liu J. Guo L. Chen G. Fang Y. Yang Y. Combining network pharmacology, molecular docking and preliminary experiments to explore the mechanism of action of FZKA formula on non-small cell lung cancer. Protein Pept. Lett. 2023 30 12 1038 1047 10.2174/0109298665268153231024111622 37962044
    [Google Scholar]
  12. Zhao M. Feng L. Li W. Network pharmacology and experimental verification: SanQi-DanShen treats coronary heart disease by inhibiting the PI3K/AKT signaling pathway. Drug Des. Devel. Ther. 2024 18 4529 4550 10.2147/DDDT.S480248 39399124
    [Google Scholar]
  13. Ye J. Yang R. Li L. Zhong S. Jiang R. Hu Z. Molecular mechanism of Danxiong Tongmai Granules in treatment of coronary heart disease. Aging 2024 16 10 8843 8865 10.18632/aging.205845 38775721
    [Google Scholar]
  14. Xia K. Zhang X. Zhang H. Su K. Shang E. Xiao Q. Li W. Guo S. Duan J. Liu P. Network pharmacology analysis and experimental verification of the antithrombotic active compounds of trichosanthis pericarpium (Gualoupi) in treating coronary heart disease. J. Ethnopharmacol. 2024 329 118158 10.1016/j.jep.2024.118158 38614263
    [Google Scholar]
  15. Feng H. Wang Z. Wang C. Zhu X. Liu Z. Liu H. Guo M. Hou Q. Chu Z. Effect of furostanol saponins from allium macrostemon bunge bulbs on platelet aggregation rate and PI3K/Akt pathway in the rat model of coronary heart disease. Evid. Based Complement. Alternat. Med. 2019 2019 1 7 10.1155/2019/9107847 31341503
    [Google Scholar]
  16. Yin C. Lan T. Wu Y. Cai J. Li H. Kuang X. Jiao L. Ou X. Yang H. Liu B. Lu W. Integrating network pharmacology and experimental validation to investigate the mechanism of qushi huatan decoction against coronary heart disease. Drug Des. Devel. Ther. 2024 18 4033 4049 10.2147/DDDT.S463054 39280256
    [Google Scholar]
  17. Chen X. Wan W. Guo Y. Ye T. Fo Y. Sun Y. Qu C. Yang B. Zhang C. Pinocembrin ameliorates post-infarct heart failure through activation of Nrf2/HO-1 signaling pathway. Mol. Med. 2021 27 1 100 10.1186/s10020‑021‑00363‑7 34488618
    [Google Scholar]
  18. Zhang Y. Yu C. Feng Y. Pinocembrin ameliorates lipopolysaccharide induced HK 2 cell apoptosis and inflammation by regulating endoplasmic reticulum stress. Exp. Ther. Med. 2022 24 2 513 10.3892/etm.2022.11440 35837041
    [Google Scholar]
  19. Gan W. Li X. Cui Y. Xiao T. Liu R. Wang M. Wei Y. Cui M. Ren S. Helian K. Ning W. Zhou H. Yang C. Pinocembrin relieves lipopolysaccharide and bleomycin induced lung inflammation via inhibiting TLR4-NF-κB-NLRP3 inflammasome signaling pathway. Int. Immunopharmacol. 2021 90 107230 10.1016/j.intimp.2020.107230 33290968
    [Google Scholar]
  20. Li C. Wan W. Ye T. Sun Y. Chen X. Liu X. Shi S. Zhang Y. Qu C. Yang B. Zhang C. Pinocembrin alleviates lipopolysaccharide-induced myocardial injury and cardiac dysfunction in rats by inhibiting p38/JNK MAPK pathway. Life Sci. 2021 277 119418 10.1016/j.lfs.2021.119418 33781824
    [Google Scholar]
  21. Zheng Y. Wan G. Yang B. Gu X. Lin J. Cardioprotective natural compound pinocembrin attenuates acute ischemic myocardial injury via enhancing glycolysis. Oxid. Med. Cell. Longev. 2020 2020 1 13 10.1155/2020/4850328 33178386
    [Google Scholar]
  22. Wen J. Yang Y. Li L. Xie J. Yang J. Zhang F. Duan L. Hao J. Tong Y. He Y. Magnoflorine alleviates dextran sulfate sodium‐induced ulcerative colitis via inhibiting JAK2/STAT3 signaling pathway. Phytother. Res. 2024 38 9 4592 4613 10.1002/ptr.8271 39079890
    [Google Scholar]
  23. Wang L. Li P. Zhou Y. Gu R. Lu G. Zhang C. Magnoflorine ameliorates collagen-induced arthritis by suppressing the inflammation response via the NF-κB/MAPK signaling pathways. J. Inflamm. Res. 2023 16 2271 2296 10.2147/JIR.S406298 37265745
    [Google Scholar]
  24. Zhu M. Hu J. Pan Y. Jiang Q. Shu C. Magnoflorine attenuates Ang II-induced cardiac remodeling via promoting AMPK-regulated autophagy. Cardiovasc. Diagn. Ther. 2024 14 4 576 588 10.21037/cdt‑24‑130 39263476
    [Google Scholar]
  25. Jiang W. Duan W.B. Li S. Shen X.Y. Zhou Y. Luo T. He F. Xu J. Wang H.Q. Jatrorrhizine protects against okadaic acid induced oxidative toxicity through inhibiting the mitogen-activated protein kinases pathways in HT22 hippocampal neurons. CNS Neurol. Disord. Drug Targets 2015 14 10 1334 1342 10.2174/1871527314666150821104455 26295822
    [Google Scholar]
  26. Sun Y. Gao X. Wu P. Wink M. Li J. Dian L. Liang Z. Jatrorrhizine inhibits mammary carcinoma cells by targeting TNIK mediated Wnt/β-catenin signalling and epithelial-mesenchymal transition (EMT). Phytomedicine 2019 63 153015 10.1016/j.phymed.2019.153015 31302315
    [Google Scholar]
  27. Hao M. Jiao K. Jatrorrhizine reduces myocardial infarction-induced apoptosis and fibrosis through inhibiting p53 and TGF-β1/Smad2/3 pathways in mice. Acta Cir. Bras. 2022 37 7 e370705 10.1590/acb370705 36327404
    [Google Scholar]
  28. Feng T. Xu Q. Yu Z. Song F. Luo Q. Wang S. Tang H. Li H. Exploring the underlying mechanisms of Danshen-Shanzha Decoction on coronary heart disease: An integrated analysis combining pharmacoinformatics and experimental validation. J. Ethnopharmacol. 2025 337 Pt 1 118779 10.1016/j.jep.2024.118779 39244177
    [Google Scholar]
  29. Fei C. Ji D. Tong H. Li Y. Su L. Qin Y. Bian Z. Zhang W. Mao C. Li L. Lu T. Therapeutic mechanism of Curcuma aromatica Salisb. rhizome against coronary heart disease based on integrated network pharmacology, pharmacological evaluation and lipidomics. Front. Pharmacol. 2022 13 950749 10.3389/fphar.2022.950749 36016561
    [Google Scholar]
  30. Kiszałkiewicz J.M. Majewski S. Piotrowski W.J. Górski P. Pastuszak-Lewandoska D. Migdalska-Sęk M. Brzeziańska-Lasota E. Evaluation of selected IL6/STAT3 pathway molecules and miRNA expression in chronic obstructive pulmonary disease. Sci. Rep. 2021 11 1 22756 10.1038/s41598‑021‑01950‑8 34815425
    [Google Scholar]
  31. Fengjiao J. Zhaozhen W. Xiao H. Jiahui Z. Zihe G. Xiao H. Junfang Q. Chen L. Yue W. The PI3K/Akt/GSK-3β/ROS/eIF2B pathway promotes breast cancer growth and metastasis via suppression of NK cell cytotoxicity and tumor cell susceptibility. Cancer Biol. Med. 2019 16 1 38 54 10.20892/j.issn.2095‑3941.2018.0253 31119045
    [Google Scholar]
  32. Tsuji-Tamura K. Ogawa M. Inhibition of the PI3K–Akt and mTORC1 signaling pathways promotes the elongation of vascular endothelial cells. J. Cell Sci. 2016 129 6 1165 1178 10.1242/jcs.178434 26826185
    [Google Scholar]
  33. Wang H. Qi Y. Lan Z. Liu Q. Xu J. Zhu M. Yang T. Shi R. Gao S. Liang G. Exosomal PD-L1 confers chemoresistance and promotes tumorigenic properties in esophageal cancer cells via upregulating STAT3/miR-21. Gene Ther. 2023 30 1-2 88 100 10.1038/s41434‑022‑00331‑8 35440807
    [Google Scholar]
  34. He B. Shao B. Cheng C. Ye Z. Yang Y. Fan B. Xia H. Wu H. Liu Q. Zhang J. miR-21-mediated endothelial senescence and dysfunction are involved in cigarette smoke-induced pulmonary hypertension through activation of PI3K/AKT/mTOR signaling. Toxics 2024 12 6 396 10.3390/toxics12060396 38922076
    [Google Scholar]
  35. Duan Z.W. Liu Y. Zhang P.P. Hu J.Y. Mo Z.X. Liu W.Q. Ma X. Zhou X.H. Wang X.H. Hu X.H. Wei S.L. Da-Chai-Hu-Tang formula inhibits the progression and metastasis in HepG2 cells through modulation of the PI3K/AKT/STAT3-induced cell cycle arrest and apoptosis. J. Ethnopharmacol. 2024 331 118293 10.1016/j.jep.2024.118293 38705430
    [Google Scholar]
  36. Yang K. Zeng L. Li Y. Wu L. Xiang W. Wu X. Wang G. Bao T. Huang S. Yu R. Zhang G. Liu H. Uncovering the pharmacological mechanism of Shou Tai Wan on recurrent spontaneous abortion: A integrated pharmacology strategy-based research. J. Ethnopharmacol. 2024 323 117589 10.1016/j.jep.2023.117589 38104875
    [Google Scholar]
  37. Kato K. Takahashi M. Oh-hashi K. Ando K. Hirata Y. Quercetin and resveratrol inhibit ferroptosis independently of Nrf2–ARE activation in mouse hippocampal HT22 cells. Food Chem. Toxicol. 2023 172 113586 10.1016/j.fct.2022.113586 36584933
    [Google Scholar]
  38. Zhu X. He L. Gao W. Zhao Z. Neuroprotective investigation of tanshinone in the cerebral infarction model in the Keap1-Nrf2/ARE pathway. Cell Cycle 2023 22 4 390 402 10.1080/15384101.2022.2119687 36066030
    [Google Scholar]
/content/journals/cchts/10.2174/0113862073426600251020060402
Loading
Network Pharmacology Analysis and Experimental Validation Reveal the Mechanism of Action of Longlutong Decoction in the Treatment of
Bentham Science Publishers ; https://doi.org/10.2174/0113862073426600251020060402
/content/journals/cchts/10.2174/0113862073426600251020060402
/content/journals/cchts/10.2174/0113862073426600251020060402
Loading

Data & Media loading...

Supplements

Supplementary material is available on the publisher's website along with the published article.

file format download Download

  • Article Type:     Research Article
Keywords: network pharmacology. formic acid ; Coronary heart disease ; mechanistic investigation ; longlutong decoction ; experimental validation

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