Investigation of the Molecular Mechanisms Underlying the Therapeutic Effect of Perilla frutescens L. Essential Oil on Acute Lung Injury Using Gas Chromatography-Mass Spectrometry and Network Pharmacology


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Abstract

Objective:The present study aimed to investigate the molecular mechanism through which Perilla essential oil treats acute lung injury (ALI) through network pharmacology, molecular docking, and in vitro assays.

Methods:Relevant ALI targets of the active ingredients of Perilla essential oil were predicted using the SwissTargetPrediction database and meta TarFisher database. These ALI targets were then screened using GeneCards and DisGeNET, and differentially expressed ALI target genes were identified using the Gene Expression Omnibus (GEO) database. Next, key targets were enriched using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Protein-protein interaction network analysis was performed to obtain targets with the highest degree values for molecular docking with Perilla essential oil active ingredients. For in vitro experiments, lipopolysaccharide (LPS) was used to induce an ALI inflammation model using RAW264.7 cells. The model cells were then treated with Perilla essential oil to detect the protein expression levels of vascular endothelial factor (NO), tumor necrosis factor (TNF-α), and p65 nuclear transcription factor in them.

Results:Sixty-eight key targets of Perilla oil were identified for the treatment of ALI. These targets were found to be involved in biological processes related to peptides, response to lipopolysaccharides, the positive regulation of cytokine production, etc., using GO. The signaling pathways found to be associated with the targets included the AGE-RAGE signaling pathway in diabetic complications, the NF-kappa B signaling pathway, and small cell lung cancer and other inflammatory signaling pathways. The five key targets that showed good binding activity with Perilla oil active ingredients included TNF, RELA, PARP1, PTGS2, and IRAK4. In vitro assays showed that Perilla essential oil could significantly reduce NO and TNF-α levels and inhibit the phosphorylation of nuclear transcription factor P65, thus inhibiting the activation of NF-κB signaling pathway.

Conclusion:Perilla essential oil can play a role in the treatment of ALI by inhibiting the activation of the NF-κB signaling pathway and preventing an excessive inflammatory response. This study thus provides a reference for the in-depth study of the mechanisms through which Perilla essential oil treats ALI.

About the authors

Hou Chen

School of Pharmaceutical and Chemical Engineering,, Yangling Vocational and Technical College

Author for correspondence.
Email: info@benthamscience.net

Lu Bai

, Xi'an No.1 Hospital,

Email: info@benthamscience.net

Yanqiong Shi

, Shanghai Xuhui District Central Hospital,

Email: info@benthamscience.net

Xiaofei Zhang

School of pharmacy, Shaanxi University of Chinese Medicine

Email: info@benthamscience.net

Xuan Wang

School of pharmacy, Shaanxi University of Chinese Medicine

Email: info@benthamscience.net

Yujiao Wang

School of pharmacy, Shaanxi University of Chinese Medicine

Email: info@benthamscience.net

Jiadong Hu

School of Pharmaceutical and Chemical Engineering, Yangling Vocational and Technical College

Email: info@benthamscience.net

Peijie Zhou

School of pharmacy, Shaanxi University of Chinese Medicine

Email: info@benthamscience.net

References

  1. Wang, Y.; Yuan, Y.; Wang, W.; He, Y.; Zhong, H.; Zhou, X.; Chen, Y.; Cai, X.J.; Liu, L. Mechanisms underlying the therapeutic effects of Qingfeiyin in treating acute lung injury based on GEO datasets, network pharmacology and molecular docking. Comput. Biol. Med., 2022, 145, 105454. doi: 10.1016/j.compbiomed.2022.105454 PMID: 35367781
  2. Zhu, H.; Wang, S.; Shan, C.; Li, X.; Tan, B.; Chen, Q.; Yang, Y.; Yu, H.; Yang, A. Mechanism of protective effect of xuan-bai-cheng-qi decoction on LPS-induced acute lung injury based on an integrated network pharmacology and RNA-sequencing approach. Respir. Res., 2021, 22(1), 188. doi: 10.1186/s12931-021-01781-1 PMID: 34183011
  3. Qi, J.J. Effects of cold exposure on TLR4/NF-κB signaling pathway in mice with endotoxic acute lung injury; Yanbian University, 2020.
  4. Wang, H.F. Mechanisms of NLRP1 inflammatory vesicles via TLR4/NF-кB pathway in acute lung injury; Hainan Medical College, 2022.
  5. Fan, E.; Brodie, D.; Slutsky, A.S. Acute respiratory distress syndrome. JAMA, 2018, 319(7), 698-710. doi: 10.1001/jama.2017.21907 PMID: 29466596
  6. Jiao, R.; Han, Z.; Ma, J.; Wu, S.; Wang, Z.; Zhou, G.; Liu, X.; Li, J.; Yan, X.; Meng, A. Irisin attenuates fine particulate matter induced acute lung injury by regulating Nod2/NF-κB signaling pathway. Immunobiology, 2023, 228(3), 152358. doi: 10.1016/j.imbio.2023.152358 PMID: 37003140
  7. Zhou, Q.; He, D.X.; Deng, Y.L.; Wang, C.L.; Zhang, L.L.; Jiang, F.M.; Irakoze, L.; Liang, Z.A. MiR-124-3p targeting PDE4B attenuates LPS-induced ALI through the TLR4/NF-κB signaling pathway. Int. Immunopharmacol., 2022, 105, 108540. doi: 10.1016/j.intimp.2022.108540 PMID: 35063752
  8. Zhou, P.; Wang, X.; Zhao, Y.; She, X.; Jia, Y.; Wang, W.; Li, J.; Luo, X. Evaluation of the mechanism of action of rosemary volatile oil in the treatment of Alzheimer’s disease using gas chromatography-mass spectrometry analysis and network pharmacology. Comb. Chem. High Throughput Screen., 2023, 26(13), 2321-2332. doi: 10.2174/1386207325666220930091758 PMID: 36200249
  9. Li, S.; Zhang, B. Traditional Chinese medicine network pharmacology: Theory, methodology and application. Chin. J. Nat. Med., 2013, 11(2), 110-120. doi: 10.1016/S1875-5364(13)60037-0 PMID: 23787177
  10. Mutlu-Ingok, A.; Devecioglu, D.; Dikmetas, D.N.; Karbancioglu-Guler, F.; Capanoglu, E. Antibacterial, antifungal, antimycotoxigenic, and antioxidant activities of essential oils: An updated review. Molecules, 2020, 25(20), 4711. doi: 10.3390/molecules25204711 PMID: 33066611
  11. Lucca, L.G.; Romão, P.R.T.; Vignoli-Silva, M.; da Veiga-Junior, V.F.; Koester, L.S. In vivo acute anti-inflammatory activity of essential oils: A review. Mini Rev. Med. Chem., 2022, 22(11), 1495-1515. doi: 10.2174/1389557521666211123091541 PMID: 34814816
  12. de Andrade, T.; Brasil, G.; Endringer, D.; da Nóbrega, F.; de Sousa, D. Cardiovascular activity of the chemical constituents of essential oils. Molecules, 2017, 22(9), 1539. doi: 10.3390/molecules22091539 PMID: 28926969
  13. Amorati, R.; Foti, M.C.; Valgimigli, L. Antioxidant activity of essential oils. J. Agric. Food Chem., 2013, 61(46), 10835-10847. doi: 10.1021/jf403496k PMID: 24156356
  14. de Sousa, D.; Silva, R.; Silva, E.; Gavioli, E. Essential oils and their constituents: An alternative source for novel antidepressants. Molecules, 2017, 22(8), 1290. doi: 10.3390/molecules22081290 PMID: 28771213
  15. Gioffrè, G.; Ursino, D.; Labate, C.; Giuffrè, A. The peel essential oil composition of bergamot fruit (Citrus bergamia, Risso) of Reggio Calabria (Italy): A review. Emir. J. Food Agric., 2021, 32, 835-845.
  16. Said-Al Ahl, H.A.H.; Sabra, A.S.; Gendy, A.S.H.; Astatkie, T. Essential oil content and concentration of constituents of lemon balm (melissa officinalis L.) at different harvest dates. J. Essent. Oil-Bear. Plants, 2018, 21(5), 1410-1417. doi: 10.1080/0972060X.2018.1553636
  17. Verzera, A.; Russo, C.; Rosa, G.L.; Bonaccorsi, I.; Cotroneo, A. Influence of cultivar on lemon oil composition. J. Essent. Oil Res., 2001, 13(5), 343-347. doi: 10.1080/10412905.2001.9712228
  18. Donelian, A.; Carlson, L.H.C.; Lopes, T.J.; Machado, R.A.F. Comparison of extraction of patchouli (Pogostemon cablin) essential oil with supercritical CO2 and by steam distillation. J. Supercrit. Fluids, 2009, 48(1), 15-20. doi: 10.1016/j.supflu.2008.09.020
  19. Ebrahimi, S.; Paryad, E.; Ghanbari Khanghah, A.; Pasdaran, A.; Kazemnezhad Leili, E.; Sadeghi Meibodi, A.M. The effects of lavandula aromatherapy on pain relief after coronary artery bypass graft surgery: A randomized clinical trial. Appl. Nurs. Res., 2022, 68, 151638. doi: 10.1016/j.apnr.2022.151638 PMID: 36473717
  20. McDonnell, B.; Newcomb, P. Trial of essential oils to improve sleep for patients in cardiac rehabilitation. J. Altern., 2022, 25(12), 1193-1199.
  21. Tarik, A.; Fatouma, M.; Baghouz, A.; Montassir, Z.; Attahar, W. Essential oils rich in pulegone for insecticide purpose against legume bruchus species: Case of Ziziphora hispanica L. and Mentha pulegium L. AIMS Agric. Food, 2022, 8, 105-118.
  22. Wang, X.F.; Li, H.; Jiang, K.; Wang, Q.Q.; Zheng, Y.H.; Tang, W.; Tan, C.H. Anti-inflammatory constituents from Perilla frutescens on lipopolysaccharide-stimulated RAW264.7 cells. Fitoterapia, 2018, 130, 61-65. doi: 10.1016/j.fitote.2018.08.006 PMID: 30121232
  23. Li, Y.Y.; Wei, K.Q.; Wu, J.; Wei, Z.Z. Introduction of medicinal plant Perilla genes into tobacco to interfere with smoking-related lung injury in rats. Nat. Prod. Res., 2016, 28(12), 1891-1895.
  24. Wang, F.Y.; Li, S.C.; Wang, X.R. Effects of Dunhuang ancient formula "Zishu Decoction" on histomorphological changes of lung in rats with chronic bronchitis. Gansu Zhongyi Xueyuan Xuebao, 2008, (02), 5-8.
  25. Wang, Y.Q.; Xing, F.Y.; Liu, F.L. Pharmacological study on the cough suppressing, expectorant and asthma calming effects of Perilla frutescens. Zhongnan Pharmacology., 2003, (03), 135-138.
  26. Wang, W.J.; Liu, X.M.; Zhang, G.Q. Study on the effect of perilla frutescens polysaccharide on airway inflammatory response and airway remodeling in rats with chronic obstructive pulmonary disease through Wnt/PCP pathway. J. Chin. Med., 2021, 27(10), 37-41. J.
  27. Cheng, D.W. Study on preparation and quality standards of compound apricot cough syrup. Asia-Pacific Traditional Medicine., 2013, 9(11), 38-39.
  28. Chen, F.; Liu, S.; Zhao, Z.; Gao, W.; Ma, Y.; Wang, X.; Yan, S.; Luo, D. Ultrasound pre-treatment combined with microwave-assisted hydrodistillation of essential oils from Perilla frutescens (L.) Britt. leaves and its chemical composition and biological activity. Ind. Crops Prod., 2020, 143, 111908. doi: 10.1016/j.indcrop.2019.111908
  29. Wei, C.L.; Zhang, C.W.; Guo, B.L. Exploring the factors influencing the chemotypes and components of the volatile oil of Perilla frutescens I--different growth and development stages. J. Tradit., 2017, 42(04), 712-718.
  30. Hu, J.H.; Liu, L.L.; Zhang, Y.J.; Xiao, W. Determination of cafferic acid and rosmarinic acid in Perilla frutescens leaves and Schizonepeta tenuifolia by HPLC. Chin. Herb. Med., 2015, 46, 2155-2159.
  31. Han, L.; Wang, Q.Y.; Lin, H. Comparison of the clinical effects of paediatric sensitization oral liquid and paediatric quick-acting cold granules in the treatment of wind-cold flu. Chin. Contemp. Med., 2015, 22(5), 149-150.
  32. Feng, S.H.; Shen, Q.; Chen, S. Essential oil profiles of 168 perilla cultivars by head space solid phase micro-extraction gas chromatography mass spectrometry. J. Essent. Oil-Bear. Plants, 2019, 22(6), 1519-1536. doi: 10.1080/0972060X.2019.1692698
  33. Ahmed, H.M.; Al-Zubaidy, A.M.A. Exploring natural essential oil components and antibacterial activity of solvent extracts from twelve Perilla frutescens L. Genotypes. Arab. J. Chem., 2020, 13(10), 7390-7402. doi: 10.1016/j.arabjc.2020.08.016
  34. Xu, X.; Tang, Z.; Liang, Y. Comparative analysis of plant essential oils by GC-MS coupled with integrated chemometric resolution methods. Anal. Methods, 2010, 2(4), 359. doi: 10.1039/b9ay00213h
  35. Fang, X.; Abbott, J.; Cheng, L.; Colby, J.K.; Lee, J.W.; Levy, B.D.; Matthay, M.A. Human mesenchymal stem (stromal) cells promote the resolution of acute lung injury in part through lipoxin A4. J. Immunol., 2015, 195(3), 875-881. doi: 10.4049/jimmunol.1500244 PMID: 26116507
  36. Liu, S; Wang, Z; Zhu, R; Wang, F; Cheng, Y; Liu, Y Three differential expression analysis methods for RNA sequencing: limma, EdgeR, DESeq2. J. Vis. Exp, 2021, (175)
  37. Otasek, D.; Morris, J.H.; Bouças, J.; Pico, A.R.; Demchak, B. Cytoscape Automation: Empowering workflow-based network analysis. Genome Biol., 2019, 20(1), 185. doi: 10.1186/s13059-019-1758-4 PMID: 31477170
  38. Szklarczyk, D.; Gable, A.L.; Nastou, K.C.; Lyon, D.; Kirsch, R.; Pyysalo, S.; Doncheva, N.T.; Legeay, M.; Fang, T.; Bork, P.; Jensen, L.J.; von Mering, C. The STRING database in 2021: Customizable protein–protein networks, and functional characterization of user-uploaded gene/measurement sets. Nucleic Acids Res., 2021, 49(D1), D605-D612. doi: 10.1093/nar/gkaa1074 PMID: 33237311
  39. Sang, L.; Sun, L.; Wang, A.; Zhang, H.; Yuan, Y. The N6-methyladenosine features of mRNA and aberrant expression of m6A modified genes in gastric cancer and their potential impact on the risk and prognosis. Front. Genet., 2020, 11, 561566. doi: 10.3389/fgene.2020.561566 PMID: 33329697
  40. Wu, T.; Hu, E.; Xu, S.; Chen, M.; Guo, P.; Dai, Z.; Feng, T.; Zhou, L.; Tang, W.; Zhan, L.; Fu, X.; Liu, S.; Bo, X.; Yu, G. clusterProfiler 4.0: A universal enrichment tool for interpreting omics data. Innovation, 2021, 2(3), 100141. doi: 10.1016/j.xinn.2021.100141 PMID: 34557778
  41. Zhong, H.; Zhao, M.; Wu, C.; Zhang, J.; Chen, L.; Sun, J. Development of oxoisoaporphine derivatives with topoisomerase I inhibition and reversal of multidrug resistance in breast cancer MCF-7/ADR cells. Eur. J. Med. Chem., 2022, 235, 114300. doi: 10.1016/j.ejmech.2022.114300 PMID: 35339100
  42. Fanelli, V.; Ranieri, V.M. Mechanisms and clinical consequences of acute lung injury. Ann. Am. Thorac. Soc., 2015, 12(Suppl. 1), S3-S8. doi: 10.1513/AnnalsATS.201407-340MG PMID: 25830831
  43. Gaab, J.; Rohleder, N.; Heitz, V.; Engert, V.; Schad, T.; Schürmeyer, T.H.; Ehlert, U. Stress-induced changes in LPS-induced pro-inflammatory cytokine production in chronic fatigue syndrome. Psychoneuroendocrinology, 2005, 30(2), 188-198. doi: 10.1016/j.psyneuen.2004.06.008 PMID: 15471616
  44. Shi, J.R.; Mao, L.G.; Jiang, R.A.; Qian, Y.; Tang, H.F.; Chen, J.Q. Monoammonium glycyrrhizinate inhibited the inflammation of LPS-induced acute lung injury in mice. Int. Immunopharmacol., 2010, 10(10), 1235-1241. doi: 10.1016/j.intimp.2010.07.004 PMID: 20637836
  45. Wang, Y.; Hu, B.; Feng, S.; Wang, J.; Zhang, F. Target recognition and network pharmacology for revealing anti-diabetes mechanisms of natural product. J. Comput. Sci., 2020, 45, 101186. doi: 10.1016/j.jocs.2020.101186
  46. Chin, Y.F.; Tang, W.F.; Chang, Y.H.; Chang, T-Y.; Lin, W-C.; Lin, C-Y.; Yang, C-M.; Wu, H-L.; Li, P-C.; Sun, J-R.; Hsu, S-C.; Lee, C-Y.; Lu, H-Y.; Chang, J-Y.; Jheng, J-R.; Chen, C.C.; Kau, J-H.; Huang, C-H.; Chiu, C-H.; Hung, Y-J.; Tsai, H-P.; Horng, J-T. Orally delivered perilla (Perilla frutescens) leaf extract effectively inhibits SARS-CoV-2 infection in a Syrian hamster model. Yao Wu Shi Pin Fen Xi, 2022, 30(2), 252-270. doi: 10.38212/2224-6614.3412
  47. Millar, M.W.; Fazal, F.; Rahman, A. Therapeutic targeting of NF-κB in acute lung injury: A double-edged sword. Cells, 2022, 11(20), 3317. doi: 10.3390/cells11203317 PMID: 36291185
  48. Malaviya, R.; Laskin, J.D.; Laskin, D.L. Anti-TNFα therapy in inflammatory lung diseases. Pharmacol. Ther., 2017, 180, 90-98. doi: 10.1016/j.pharmthera.2017.06.008 PMID: 28642115
  49. Shen, W.; Gan, J.; Xu, S.; Jiang, G.; Wu, H. Penehyclidine hydrochloride attenuates LPS-induced acute lung injury involvement of NF-κB pathway. Pharmacol. Res., 2009, 60(4), 296-302. doi: 10.1016/j.phrs.2009.04.007 PMID: 19386282
  50. McVey, M.J.; Steinberg, B.E.; Goldenberg, N.M. Inflammasome activation in acute lung injury. Am. J. Physiol. Lung Cell. Mol. Physiol., 2021, 320(2), L165-L178. doi: 10.1152/ajplung.00303.2020 PMID: 33296269
  51. Jiang, B.; Chu, Z.X. Nitric oxide and inflammation. Foreign Medicine, 1998, 1998(01), 44-47.
  52. Hayden, M.S.; Ghosh, S. Regulation of NF-κB by TNF family cytokines. Semin. Immunol., 2014, 26(3), 253-266. doi: 10.1016/j.smim.2014.05.004 PMID: 24958609

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