Network pharmacology integrated with experimental verification reveals the antipyretic characteristics and mechanism of Zi Xue powder.

Hanyu Zhang, Shining Ge, Fengyin Diao, Wen Song, Ying Zhang, Pengwei Zhuang, Yanjun Zhang
Author Information
  1. Hanyu Zhang: College of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, China.
  2. Shining Ge: College of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, China.
  3. Fengyin Diao: College of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, China.
  4. Wen Song: Tianjin Hongrentang Pharmaceutical Co., Ltd, Tianjin, China.
  5. Ying Zhang: Tianjin Hongrentang Pharmaceutical Co., Ltd, Tianjin, China.
  6. Pengwei Zhuang: College of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, China.
  7. Yanjun Zhang: State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.

Abstract

CONTEXT: Zi Xue Powder (ZXP) is a traditional formula for the treatment of fever. However, the potential mechanism of action of ZXP remains unknown.
OBJECTIVE: This study elucidates the antipyretic characteristics of ZXP and the mechanism by which ZXP alleviates fever.
MATERIALS AND METHODS: The key targets and underlying fever-reducing mechanisms of ZXP were predicted using network pharmacology and molecular docking. The targets of ZXP anti-fever active ingredient were obtained by searching TCMSP, STITCH and HERB. Moreover, male Sprague-Dawley rats were randomly divided into four groups: control, lipopolysaccharide (LPS), ZXP (0.54, 1.08, 2.16 g/kg), and positive control (acetaminophen, 0.045 g/kg); the fever model was established by intraperitoneal LPS injection. After the fever model was established at 0.5 h, the rats were administered treatment by gavage, and the anal temperature changes of each group were observed over 10 h after treatment. After 10 h, ELISA and Western blot analysis were used to further investigate the mechanism of ZXP.
RESULTS: Network pharmacology analysis showed that MAPK was a crucial pathway through which ZXP suppresses fever. The results showed that ZXP (2.16 g/kg) decreased PGE2, CRH, TNF-a, IL-6, and IL-1β levels while increasing AVP level compared to the LPS group. Furthermore, the intervention of ZXP inhibited the activation of MAPK pathway in LPS-induced fever rats.
CONCLUSIONS: This study provides new insights into the mechanism by which ZXP reduces fever and provides important information and new research ideas for the discovery of antipyretic compounds from traditional Chinese medicine.

Keywords

References

  1. Comput Biol Med. 2022 May;144:105389 [PMID: 35303581]
  2. Nucleic Acids Res. 2000 Jan 1;28(1):235-42 [PMID: 10592235]
  3. Am J Physiol. 1999 Jun;276(6):R1840-4 [PMID: 10362768]
  4. Acta Biochim Biophys Sin (Shanghai). 2019 Apr 1;51(4):365-374 [PMID: 30877761]
  5. Oncogene. 2007 Mar 1;26(10):1385-97 [PMID: 16953224]
  6. Pharmacol Res. 2022 Jan;175:106000 [PMID: 34838694]
  7. Chin Herb Med. 2022 Sep 01;14(4):554-562 [PMID: 36405054]
  8. Stroke. 2021 Jul;52(7):2284-2291 [PMID: 33910366]
  9. J Cheminform. 2014 Apr 16;6:13 [PMID: 24735618]
  10. Dig Dis Sci. 2012 Feb;57(2):355-63 [PMID: 21901258]
  11. J Cell Mol Med. 2020 May;24(9):5039-5056 [PMID: 32220053]
  12. Biochem Pharmacol. 2003 Nov 1;66(9):1809-19 [PMID: 14563491]
  13. Ther Hypothermia Temp Manag. 2020 Sep;10(3):148-152 [PMID: 31895653]
  14. Mol Immunol. 2020 Dec;128:139-149 [PMID: 33126082]
  15. Front Immunol. 2021 Feb 19;11:587229 [PMID: 33679687]
  16. Mol Immunol. 2009 Mar;46(6):1179-88 [PMID: 19118901]
  17. Biomed Pharmacother. 2020 Mar;123:109753 [PMID: 31865148]
  18. Mediators Inflamm. 2016;2016:5678046 [PMID: 27630451]
  19. Nucleic Acids Res. 2021 Jan 8;49(D1):D1388-D1395 [PMID: 33151290]
  20. Neuroscientist. 2018 Aug;24(4):381-399 [PMID: 29557255]
  21. Database (Oxford). 2010 Aug 05;2010:baq020 [PMID: 20689021]
  22. Pharmacol Res. 2021 Dec;174:105971 [PMID: 34763093]
  23. Arch Physiol Biochem. 2020 Oct;126(4):300-307 [PMID: 30406686]
  24. Nucleic Acids Res. 2003 Jan 1;31(1):258-61 [PMID: 12519996]
  25. Phytomedicine. 2020 Aug;74:152815 [PMID: 30833146]
  26. Int J Hyperthermia. 2015;31(7):793-9 [PMID: 26367316]
  27. Nucleic Acids Res. 2021 Jan 8;49(D1):D1197-D1206 [PMID: 33264402]
  28. Acta Neurol Scand. 2010 Dec;122(6):404-8 [PMID: 20199523]
  29. Mol Cell Biol. 2013 Nov;33(21):4152-65 [PMID: 23979601]
  30. J Food Biochem. 2021 Jul 8;:e13851 [PMID: 34236082]
  31. Paediatr Drugs. 2022 Nov;24(6):603-655 [PMID: 36053397]
  32. JAMA Netw Open. 2020 Oct 1;3(10):e2022398 [PMID: 33125495]
  33. Front Pharmacol. 2022 May 23;13:878776 [PMID: 35677438]
  34. Nucleic Acids Res. 2015 Jan;43(Database issue):D789-98 [PMID: 25428349]
  35. Front Cell Infect Microbiol. 2021 Oct 28;11:707905 [PMID: 34778101]
  36. Am J Physiol Regul Integr Comp Physiol. 2005 Aug;289(2):R332-R339 [PMID: 15802558]
  37. Nat Chem Biol. 2008 Nov;4(11):682-90 [PMID: 18936753]
  38. Genome Biol. 2003;4(5):P3 [PMID: 12734009]
  39. Antimicrob Agents Chemother. 2020 Jun 23;64(7): [PMID: 32366711]
  40. Inflamm Res. 2002 Jan;51(1):24-32 [PMID: 11852909]
  41. Cell Signal. 2018 Aug;48:64-68 [PMID: 29753850]
  42. Cytokine. 2020 Dec;136:155241 [PMID: 32799102]
  43. Front Pharmacol. 2021 Mar 22;12:583279 [PMID: 33828481]
  44. Crit Care. 2020 Sep 3;24(1):543 [PMID: 32883332]
  45. Theranostics. 2020 Oct 30;10(26):12223-12240 [PMID: 33204339]
  46. Nucleic Acids Res. 2010 Jan;38(Database issue):D552-6 [PMID: 19897548]
  47. J Agric Food Chem. 2012 Apr 18;60(15):3947-54 [PMID: 22400806]
  48. Metabolites. 2022 Jan 27;12(2): [PMID: 35208196]
  49. Pharm Biol. 2022 Dec;60(1):87-95 [PMID: 34962453]
  50. Nucleic Acids Res. 2014 Jul;42(Web Server issue):W32-8 [PMID: 24792161]
  51. Front Microbiol. 2021 Oct 21;12:736780 [PMID: 34745038]
  52. BMC Complement Altern Med. 2018 Jul 25;18(1):224 [PMID: 30045725]
  53. Lancet. 2020 Feb 15;395(10223):497-506 [PMID: 31986264]
  54. J Exp Med. 2011 Dec 19;208(13):2615-23 [PMID: 22143887]
  55. Peptides. 2008 Nov;29(11):1937-42 [PMID: 18775757]
  56. Food Chem. 2013 Nov 15;141(2):1063-71 [PMID: 23790887]
  57. J Neurosci. 2014 Nov 26;34(48):15957-61 [PMID: 25429137]
  58. Am J Respir Crit Care Med. 2012 May 15;185(10):1088-95 [PMID: 22366046]
  59. Planta Med. 2018 Dec;84(18):1340-1347 [PMID: 29954026]
  60. Compr Physiol. 2014 Oct;4(4):1563-604 [PMID: 25428854]
  61. Gut. 2021 Feb;70(2):442-444 [PMID: 32606209]
  62. Am J Physiol Regul Integr Comp Physiol. 2005 Apr;288(4):R872-8 [PMID: 15576666]
  63. Nucleic Acids Res. 2018 Jan 4;46(D1):D1074-D1082 [PMID: 29126136]
  64. Evid Based Complement Alternat Med. 2013;2013:621423 [PMID: 23762149]
  65. Life Sci. 2003 Dec 26;74(6):709-21 [PMID: 14654164]

MeSH Term

Rats
Male
Animals
Antipyretics
Rats, Sprague-Dawley
Powders
Molecular Docking Simulation
Lipopolysaccharides
Network Pharmacology
Fever
Drugs, Chinese Herbal

Chemicals

Antipyretics
Powders
Lipopolysaccharides
Drugs, Chinese Herbal

Word Cloud

Created with Highcharts 10.0.0ZXPfevermechanismtreatmentantipyreticpharmacologyratsLPS0analysisZiXuetraditionalstudycharacteristicstargetsnetworkmolecularcontrollipopolysaccharide216 g/kgmodelestablishedgroup10 hNetworkshowedMAPKpathwayprovidesnewChinesemedicineCONTEXT:PowderformulaHoweverpotentialactionremainsunknownOBJECTIVE:elucidatesalleviatesMATERIALSANDMETHODS:keyunderlyingfever-reducingmechanismspredictedusingdockinganti-feveractiveingredientobtainedsearchingTCMSPSTITCHHERBMoreovermaleSprague-Dawleyrandomlydividedfourgroups:54108positiveacetaminophen045 g/kgintraperitonealinjection5 hadministeredgavageanaltemperaturechangesobservedELISAWesternblotusedinvestigateRESULTS:crucialsuppressesresultsdecreasedPGE2CRHTNF-aIL-6IL-1βlevelsincreasingAVPlevelcomparedFurthermoreinterventioninhibitedactivationLPS-inducedCONCLUSIONS:insightsreducesimportantinformationresearchideasdiscoverycompoundsintegratedexperimentalverificationrevealspowderFeverbiological

Similar Articles

Cited By