The mechanism and active compounds of semen armeniacae amarum treating coronavirus disease 2019 based on network pharmacology and molecular docking

  • Yuehua Wang Institute of Pharmacy, Pharmaceutical College of Henan University, Jinming District, Kaifeng, Henan Province, China
  • Wenwen Gu Institute of Pharmacy, Pharmaceutical College of Henan University, Jinming District, Kaifeng, Henan Province, China
  • Fuguang Kui Institute of Pharmacy, Pharmaceutical College of Henan University, Jinming District, Kaifeng, Henan Province, China
  • Fan Gao Institute of Pharmacy, Pharmaceutical College of Henan University, Jinming District, Kaifeng, Henan Province, China
  • Yuji Niu Institute of Pharmacy, Pharmaceutical College of Henan University, Jinming District, Kaifeng, Henan Province, China
  • Wenwen Li Institute of Pharmacy, Pharmaceutical College of Henan University, Jinming District, Kaifeng, Henan Province, China
  • Yaru Zhang Institute of Pharmacy, Pharmaceutical College of Henan University, Jinming District, Kaifeng, Henan Province, China
  • Zhenzhen Guo Institute of Pharmacy, Pharmaceutical College of Henan University, Jinming District, Kaifeng, Henan Province, China
  • Gangjun Du Institute of Pharmacy, Pharmaceutical College of Henan University, Jinming District, Kaifeng, Henan Province, and School of Pharmacy and Chemical Engineering, Zhengzhou University of Industry Technology, Xinzheng, Henan Province, China
Keywords: Semen armeniacae amarum, COVID-19, Network pharmacology, Target prediction, Molecular Docking


Background: Coronavirus disease 2019 (COVID-19) outbreak is progressing rapidly, and poses significant threats to public health. A number of clinical practice results showed that traditional Chinese medicine (TCM) plays a significant role for COVID-19 treatment.

Objective: To explore the active components and molecular mechanism of semen armeniacae amarum treating COVID-19 by network pharmacology and molecular docking technology.

Methods: The active components and potential targets of semen armeniacae amarum were retrieved from traditional Chinese medicine systems pharmacology (TCMSP) database. Coronavirus disease 2019-associated targets were collected in the GeneCards, TTD, OMIM and PubChem database. Compound target, compound- target pathway and medicine-ingredient-target disease networks were constructed by Cytoscape 3.8.0. Protein-protein interaction (PPI) networks were drawn using the STRING database and Cytoscape 3.8.0 software. David database was used for gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The main active components were verified by AutoDock Vina 1.1.2 software. A lipopolysaccharide (LPS)-induced lung inflammation model in Institute of Cancer Research (ICR) mice was constructed and treated with amygdalin to confirm effects of amygdalin on lung inflammation and its underlying mechanisms by western blot analyses and immunofluorescence.

Results: The network analysis revealed that nine key, active components regulated eight targets (Protooncogene tyrosine-protein kinase SRC (SRC), interleukin 6 (IL6), mitogen-activated protein kinase 1 (MAPK1), mitogen- activated protein kinase 3 (MAPK3), vascular endothelial growth factor A (VEGFA), epidermal growth factor receptor (EGFR), HRAS proto-oncogene (HRAS), caspase-3 (CASP3)). Gene ontology and KEGG enrichment analysis suggested that semen armeniacae amarum plays a role in COVID- 19 by modulating 94 biological processes, 13 molecular functions, 15 cellular components and 80 potential pathways. Molecular docking indicated that amygdalin had better binding activity to key targets such as IL6, SRC, MAPK3, SARS coronavirus-2 3C-like protease (SARS-CoV-2 3CLpro) and SARS-CoV-2 angiotensin converting enzyme II (ACE2). Experimental validation revealed that the lung pathological injury and inflammatory injury were significantly increased in the model group and were improved in the amygdalin group.

Conclusion: Amygdalin is a candidate compound for COVID-19 treatment by regulating IL6, SRC, MAPK1 EGFR and VEGFA to involve in PI3K-Akt signalling pathway, VEGF signalling pathway and MAPK signalling pathway. Meanwhile, amygdalin has a strong affinity for SARS-CoV-2 3CLpro and SARS-CoV-2 ACE2 and therefore prevents the virus transcription and dissemination.


Download data is not yet available.


  1. Esakandari H, Nabi-Afjadi M, Fakkari-Afjadi J, Farahmandian N, Miresmaeili SM, Bahreini E. A comprehensive review of COVID-19 characteristics. Biol Proced Online 2020; 22: 19. doi: 10.1186/s12575-020-00128-2

  2. Delang L, Neyts J. Medical treatment options for COVID-19. Eur Heart J Acute Cardiovasc Care 2020; 9(3): 209–14. doi: 10.1177/2048872620922790

  3. Ren X, Shao XX, Li XX, Jia XH, Song T, Zhou WY, et al. Identifying potential treatments of COVID-19 from Traditional Chinese Medicine (TCM) by using a data-driven approach. J Ethnopharmacol 2020; 258: 112932. doi: 10.1016/j.jep.2020.112932

  4. Zhao Z, Li Y, Zhou L, Zhou X, Xie B, Zhang W, et al. Prevention and treatment of COVID-19 using Traditional Chinese Medicine: a review. Phytomedicine 2020; 20: 153308. doi: 10.1016/j.phymed.2020.153308

  5. Lin D, Lin W, Gao G, Zhou J, Chen T, Ke L, et al. Purification and characterization of the major protein isolated from Semen Armeniacae Amarum and the properties of its thermally induced nanoparticles. Int J Biol Macromol 2020; 159: 850–8. doi: 10.1016/j.ijbiomac.2020.05.070

  6. Huang L, Lv Q, Liu F, Shi T, Wen C. A systems biology-based investigation into the pharmacological mechanisms of Sheng-ma-bie-jia-tang acting on systemic Lupus Erythematosus by multi-level data integration. Sci Rep 2015; 12(5): 16401. doi: 10.1038/srep16401

  7. Zhang Y, Guo X, Wang D, Li R, Li X, Xu Y, et al. A systems biology-based investigation into the therapeutic effects of Gansui Banxia Tang on reversing the imbalanced network of hepatocellular carcinoma. Sci Rep 2014; 24(4): 4154. doi: 10.1038/srep04154

  8. Lee S. Systems biology – a pivotal research methodology for understanding the mechanisms of traditional medicine. J Pharmacopuncture 2015; 18(3): 11–18. doi: 10.3831/KPI.2015.18.020

  9. Wang S, Wang H, Lu Y. Tianfoshen oral liquid: a CFDA approved clinical traditional Chinese medicine, normalizes major cellular pathways disordered during colorectal carcinogenesis. Oncotarget 2017; 8(9): 14549–69. doi: 10.18632/oncotarget.14675

  10. Li YH, Yu CY, Li XX, Zhang P, Tang J, Yang Q, et al. Therapeutic target database update 2018: enriched resource for facilitating bench-to-clinic research of targeted therapeutics. Nucleic Acids Res 2018; 46(D1): D1121–7. doi: 10.1093/nar/gkx1076

  11. Jiang Y, Zhong M, Long F, Yang R, Zhang Y, Liu T. Network pharmacology-based prediction of active ingredients and mechanisms of Lamiophlomis rotata (Benth.) Kudo against rheumatoid arthritis. Front Pharmacol 2019; 10: 1435. doi: 10.3389/fphar.2019.01435

  12. Athanasios A, Charalampos V, Vasileios T, Ashraf GM. Protein-Protein Interaction (PPI) network: recent advances in drug discovery. Curr Drug Metab 2017; 18(1): 5–10. doi: 10.2174/138920021801170119204832

  13. Tao Q, Du J, Li X, Zeng J, Tan B, Xu J, et al. Network pharmacology and molecular docking analysis on molecular targets and mechanisms of Huashi Baidu formula in the treatment of COVID-19. Drug Dev Ind Pharm 2020; 46(8): 1345–53. doi: 10.1080/03639045.2020.1788070

  14. Zhou F, He K, Guan Y, Yang X, Chen Y, Sun M, et al. Network pharmacology-based strategy to investigate pharmacological mechanisms of Tinospora sinensis for treatment of Alzheimer’s disease. J Ethnopharmacol 2020; 259: 112940. doi: 10.1016/j.jep.2020.112940

  15. Wang X, Su R, Guo Q, Liu J, Ruan B, Wang G. Competing endogenous RNA (ceRNA) hypothetic model based on comprehensive analysis of long non-coding RNA expression in lung adenocarcinoma. PeerJ 2019; 7: e8024. doi: 10.7717/peerj.8024

  16. Gaudreault F, Morency LP, Najmanovich RJ. NRGsuite: a PyMOL plugin to perform docking simulations in real time using FlexAID. Bioinformatics 2015; 31(23): 3856–8. doi: 10.1093/bioinformatics/btv458

  17. Li Z, Lin Y, Zhang S, Zhou L, Yan G, Wang Y, et al. Emodin regulates neutrophil phenotypes to prevent hypercoagulation and lung carcinogenesis. J Transl Med 2019; 17(1): 90. doi: 10.1186/s12967-019-1838-y

  18. Zhang A, Pan W, Lv J, Wu H. Protective effect of amygdalin on LPS-induced acute lung injury by inhibiting NF-κB and NLRP3 signaling pathways. Inflammation 2017; 40(3): 745–51. doi: 10.1007/s10753-017-0518-4

  19. Park JH, Seo BI, Cho SY, Park KR, Choi SH, Han CK, et al. Single oral dose toxicity study of prebrewed armeniacae semen in rats. Toxicol Res 2013; 29(2): 91–8. doi: 10.5487/TR.2013.29.2.091

  20. Gao J, Liang L, Zhu Y, Qiu S, Wang T, Zhang L. Ligand and structure-based approaches for the identification of peptide deformylase inhibitors as antibacterial drugs. Int J Mol Sci 2016; 17(7): 1141. doi: 10.3390/ijms17071141

  21. Romagnoli S, Peris A, De Gaudio AR, Geppetti P. SARS-CoV-2 and COVID-19: from the bench to the bedside. Physiol Rev 2020; 100(4): 1455–66. doi: 10.1152/physrev.00020.2020

  22. Lim TK, Siow WT. Pneumonia in the tropics. Respirology 2018; 23(1): 28–35. doi: 10.1111/resp.13137

  23. Lin L, Yan H, Chen J, Xie H, Peng L, Xie T, et al. Application of metabolomics in viral pneumonia treatment with traditional Chinese medicine. Chin Med 2019; 14: 8. doi: 10.1186/s13020-019-0229-x

  24. Borsa N, Pasquale MD, Restrepo MI. Animal models of Pneumococcal pneumonia. Int J Mol Sci 2019; 20(17): 4220. doi: 10.3390/ijms20174220

  25. Tanwar B, Modgil R, Goyal A. Antinutritional factors and hypocholesterolemic effect of wild apricot kernel (Prunus armeniaca L.) as affected by detoxification. Food Funct 2018; 9(4): 2121–35. doi: 10.1039/c8fo00044a

  26. Song S, Ma Q, Tang Q, Chen F, Xing X, Guo Y, et al. Stereoselective metabolism of amygdalin-based study of detoxification of Semen Armeniacae Amarum in the Herba Ephedrae-Semen Armeniacae Amarum herb pair. J Ethnopharmacol 2016; 179: 356–66. doi: 10.1016/j.jep.2015.12.019

  27. Zhou R, Zhu Y, Yang W, Zhang F, Wang J, Yan R, et al. Discovery of herbal pairs containing Gastrodia elata based on data mining and the delphi expert questionnaire and their potential effects on stroke through network pharmacology. Evid Based Complement Alternat Med 2020; 2020: 4263591. doi: 10.1155/2020/4263591

  28. 28. Zhang DH, Zhang X, Peng B, Deng SQ, Wang YF, Yang L, et al. Network pharmacology suggests biochemical rationale for treating COVID-19 symptoms with a Traditional Chinese Medicine. Commun Biol 2020; 3(1): 466. doi: 10.1038/s42003-020-01190-y

  29. Xiao L, Liang S, Ge L, Qiu S, Wan H, Wu S, et al. Si-Wei-Qing-Gan-Tang improves non-alcoholic steatohepatitis by modulating the nuclear factor-κB signal pathway and autophagy in methionine and choline deficient diet-fed rats. Front Pharmacol 2020; 11: 530. doi: 10.3389/fphar.2020.00530

  30. Wang S, Ye K, Shu T, Tang X, Wang XJ, Liu S. Enhancement of Galloylation efficacy of Stigmasterol and β-Sitosterol followed by evaluation of cholesterol-reducing activity. J Agric Food Chem 2019; 67(11): 3179–87. doi: 10.1021/acs.jafc.8b06983

  31. Antwi AO, Obiri DD, Osafo N. Stigmasterol modulates allergic airway inflammation in guinea pig model of ovalbumin-induced asthma. Mediators Inflamm 2017; 2017: 2953930. doi: 10.1155/2017/2953930

  32. Yang R, Xue L, Zhang L, Wang X, Qi X, Jiang J, et al. Phytosterol contents of edible oils and their contributions to estimated phytosterol intake in the Chinese diet. Foods 2019; 8(8): 334. doi: 10.3390/foods8080334

  33. Jeong SJ, Lim HS, Seo CS, Jin SE, Yoo SR, Lee N, et al. Antiinflammatory actions of herbal formula Gyejibokryeong-hwan regulated by inhibiting chemokine production and STAT1 activation in HaCaT cells. Biol Pharm Bull 2015; 38(3): 425–34. doi: 10.1248/bpb.b14-00660

  34. Saleem M, Asif J, Asif M, Saleem U. Amygdalin from apricot kernels induces apoptosis and causes cell cycle arrest in cancer cells: an updated review. Anticancer Agents Med Chem 2018; 18(12): 1650–5. doi: 10.2174/1871520618666180105161136

  35. Lin YC, Chang CW, Wu CR. Antitussive, anti-pyretic and toxicological evaluation of Ma-Xing-Gan-Shi-Tang in rodents. BMC Complement Altern Med 2016; 16(1): 456. doi: 10.1186/s12906-016-1440-2

  36. Huang YF, Bai C, He F, Xie Y, Zhou H. Review on the potential action mechanisms of Chinese medicines in treating Coronavirus Disease 2019 (COVID-19). Pharmacol Res 2020; 158: 104939. doi: 10.1016/j.phrs.2020.104939

  37. Chen L, Hu C, Hood M, Zhang X, Zhang L, Kan J, et al. A novel combination of vitamin C, curcumin and glycyrrhizic acid potentially regulates immune and inflammatory response associated with coronavirus infections: a perspective from system biology analysis. Nutrients 2020; 12(4): 1193. doi: 10.3390/nu12041193

  38. Noack M, Miossec P. Selected cytokine pathways in rheumatoid arthritis. Semin Immunopathol 2017; 39(4): 365–83. doi: 10.1007/s00281-017-0619-z

  39. Yang Z, Kirton HM, Al-Owais M, Thireau J, Richard S, Peers C, et al. Epac2-Rap1 signaling regulates reactive oxygen species production and susceptibility to cardiac arrhythmias. Antioxid Redox Signal 2017; 27(3): 117–32. doi: 10.1089/ars.2015.6485

  40. Jin X, Di X, Wang R, Ma H, Tian C, Zhao M, et al. RBM10 inhibits cell proliferation of lung adenocarcinoma via RAP1/AKT/CREB signalling pathway. J Cell Mol Med 2019; 23(6): 3897–904. doi: 10.1111/jcmm.14263

  41. Pinzi L, Rastelli G. Molecular docking: shifting paradigms in drug discovery. Int J Mol Sci 2019; 20(18): 4331. doi: 10.3390/ijms20184331

  42. Gheblawi M, Wang K, Viveiros A, Nguyen Q, Zhong JC, Turner AJ, et al. Angiotensin-converting enzyme 2: SARS-CoV-2 receptor and regulator of the renin-angiotensin system: celebrating the 20th anniversary of the discovery of ACE2. Circ Res 2020; 126(10): 1456–74. doi: 10.1161/CIRCRESAHA.120.317015

  43. Tahir Ul Qamar M, Alqahtani SM, Alamri MA, Chen LL. Structural basis of SARS-CoV-2 3CLpro and anti-COVID-19 drug discovery from medicinal plants. J Pharm Anal 2020; 10(4): 313–9. doi: 10.1016/j.jpha.2020.03.009

  44. Kong Q, Wu Y, Gu Y, Lv Q, Qi F, Gong S, et al. Analysis of the molecular mechanism of Pudilan (PDL) treatment for COVID-19 by network pharmacology tools. Biomed Pharmacother 2020; 128: 110316. doi: 10.1016/j.biopha.2020.110316

  45. Wang Z, Chen X, Lu Y, Chen F, Zhang W. Clinical characteristics and therapeutic procedure for four cases with 2019 novel coronavirus pneumonia receiving combined Chinese and Western medicine treatment. Biosci Trends 2020; 16; 14(1): 64–8. doi: 10.5582/bst.2020.01030

  46. Liu B, Li M, Zhou Z, Guan X, Xiang Y. Can we use interleukin-6 (IL-6) blockade for coronavirus disease 2019 (COVID-19)-induced cytokine release syndrome (CRS)? J Autoimmun 2020; 111: 102452. doi: 10.1016/j.jaut.2020.102452

How to Cite
Wang Y., Gu W., Kui F., Gao F., Niu Y., Li W., Zhang Y., Guo Z., & Du G. (2021). The mechanism and active compounds of semen <em>armeniacae amarum</em&gt; treating coronavirus disease 2019 based on network pharmacology and molecular docking. Food & Nutrition Research, 65.
Original Articles