DOI QR코드

DOI QR Code

Assessment of antinociceptive property of Cynara scolymus L. and possible mechanism of action in the formalin and writhing models of nociception in mice

  • Pegah Yaghooti (Department of Basic Sciences and Pathobiology, Faculty of Veterinary Medicine, Razi University) ;
  • Samad Alimoahmmadi (Department of Basic Sciences and Pathobiology, Faculty of Veterinary Medicine, Razi University)
  • 투고 : 2023.12.18
  • 심사 : 2024.04.07
  • 발행 : 2024.07.01

초록

Background: Cynara scolymus has bioactive constituents and has been used for therapeutic actions. The present study was undertaken to investigate the mechanisms underlying pain-relieving effects of the hydroethanolic extract of C. scolymus (HECS). Methods: The antinociceptive activity of HECS was assessed through formalin and acetic acid-induced writhing tests at doses of 50, 100 and 200 mg/kg intraperitoneally. Additionally, naloxone (non-selective opioid receptors antagonist, 2 mg/kg), atropine (non-selective muscarinic receptors antagonist, 1 mg/kg), chlorpheniramine (histamine H1-receptor antagonist, 20 mg/kg), cimetidine (histamine H2-receptor antagonist, 12.5 mg/kg), flumazenil (GABAA/BDZ receptor antagonist, 5 mg/kg) and cyproheptadine (serotonin receptor antagonist, 4 mg/kg) were used to determine the systems implicated in HECS-induced analgesia. Impact of HECS on locomotor activity was executed by open-field test. Determination of total phenolic content (TPC) and total flavonoid content (TFC) was done. Evaluation of antioxidant activity was conducted employing 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging assay. Results: HECS (50, 100 and 200 mg/kg) significantly indicated dose dependent antinociceptive activity against pain-related behavior induced by formalin and acetic acid (P < 0.001). Pretreatment with naloxone, atropine and flumazenil significantly reversed HECS-induced analgesia. Antinociceptive effect of HECS remained unaffected by chlorpheniramine, cimetidine and cyproheptadine. Locomotor activity was not affected by HECS. TPC and TFC of HECS were 59.49 ± 5.57 mgGAE/g dry extract and 93.39 ± 17.16 mgRE/g dry extract, respectively. DPPH free radical scavenging activity (IC50) of HECS was 161.32 ± 0.03 ㎍/mL. Conclusions: HECS possesses antinociceptive activity which is mediated via opioidergic, cholinergic and GABAergic pathways.

키워드

과제정보

This study received financial backing from a grant provided by the Research Council of the Faculty of Veterinary Medicine at Razi University, located in Iran. The authors hereby extend their gratitude to Dr. Alireza Abdolmohammadi for his valuable aid.

참고문헌

  1. Sreekeesoon DP, Mahomoodally MF. Ethnopharmacological analysis of medicinal plants and animals used in the treatment and management of pain in Mauritius. J Ethnopharmacol 2014; 157: 181-200. 
  2. Olorukooba AB, Odoma S. Elucidation of the possible mechanism of analgesic action of methanol stem bark extract of Uapaca togoensis pax in mice. J Ethnopharmacol 2019; 245: 112156. 
  3. Mohammadifard F, Alimohammadi S. Chemical composition and role of opioidergic system in antinociceptive effect of Ziziphora Clinopodioides essential oil. Basic Clin Neurosci 2018; 9: 357-66. 
  4. Koohsari S, Sheikholeslami MA, Parvardeh S, Ghafghazi S, Samadi S, Poul YK, et al. Antinociceptive and antineuropathic effects of cuminaldehyde, the major constituent of Cuminum cyminum seeds: possible mechanisms of action. J Ethnopharmacol 2020; 255: 112786. 
  5. Ben Salem M, Affes H, Ksouda K, Dhouibi R, Sahnoun Z, Hammami S, et al. Pharmacological studies of artichoke leaf extract and their health benefits. Plant Foods Hum Nutr 2015; 70: 441-53. 
  6. Mejri F, Baati T, Martins A, Selmi S, Luisa Serralheiro M, Fale PL, et al. Phytochemical analysis and in vitro and in vivo evaluation of biological activities of artichoke (Cynara scolymus L.) floral stems: towards the valorization of food by-products. Food Chem 2020; 333: 127506. 
  7. Salekzamani S, Ebrahimi-Mameghani M, Rezazadeh K. The antioxidant activity of artichoke (Cynara scolymus): a systematic review and meta-analysis of animal studies. Phytother Res 2019; 33: 55-71. 
  8. Ben Salem M, Ben Abdallah Kolsi R, Dhouibi R, Ksouda K, Charfi S, Yaich M, et al. Protective effects of Cynara scolymus leaves extract on metabolic disorders and oxidative stress in alloxan-diabetic rats. BMC Complement Altern Med 2017; 17: 328. 
  9. Mocelin R, Marcon M, Santo GD, Zanatta L, Sachett A, Schonell AP, et al. Hypolipidemic and antiatherogenic effects of Cynara scolymus in cholesterol-fed rats. Rev Bras Farmacognosia 2016; 26: 233-9. 
  10. Ben Salem M, Affes H, Athmouni K, Ksouda K, Dhouibi R, Sahnoun Z, et al. Chemicals compositions, antioxidant and anti-inflammatory activity of Cynara scolymus leaves extracts, and analysis of major bioactive polyphenols by HPLC. Evid Based Complement Alternat Med 2017; 2017: 4951937. 
  11. Alahmoradi M, Alimohammadi S, Cheraghi H. Protective effect of Cynara scolymus L. on blood biochemical parameters and liver histopathological changes in phenylhydrazine-induced hemolytic anemia in rats. Pharm Biomed Res 2019; 5: 53-62. 
  12. Allahmoradi M, Alimohammadi S, Cheraghi H. Amelioration of lipid peroxidation and antioxidant enzymes status in the serum and erythrocytes of phenylhydrazine-induced anemic male rats: the protective role of artichoke extract (Cynara scolymus L.). Iran J Vet Med 2020; 14: 315-28. 
  13. Zimmermann M. Ethical guidelines for investigations of experimental pain in conscious animals. Pain 1983; 16: 109-10. 
  14. Kavaliers M, Hirst M. Daily rhythms of analgesia in mice: effects of age and photoperiod. Brain Res 1983; 279: 387-93. 
  15. Montiel-Ruiz RM, Gonzalez-Trujano ME, DecigaCampos M. Synergistic interactions between the antinociceptive effect of Rhodiola rosea extract and B vitamins in the mouse formalin test. Phytomedicine 2013; 20: 1280-7. 
  16. Zendehdel M, Torabi Z, Hassanpour S. Antinociceptive mechanisms of Bunium persicum essential oil in the mouse writhing test: role of opioidergic and histaminergic systems. Vet Med 2015; 60: 63-70. 
  17. Oliveira AS, Cercato LM, de Santana Souza MT, Melo AJO, Lima BDS, Duarte MC, et al. The ethanol extract of Leonurus sibiricus L. induces antioxidant, antinociceptive and topical anti-inflammatory effects. J Ethnopharmacol 2017; 206: 144-51. 
  18. Zhishen J, Mengcheng T, Jianming W. The determination of flavonoid contents in mulberry and their scavenging effects on superoxide radicals. Food Chem 1999; 64: 555-9. 
  19. Blois MS. Antioxidant determinations by the use of a stable free radical. Nature 1958; 181: 1199-200. 
  20. Khalil M, Khalifeh H, Baldini F, Salis A, Damonte G, Daher A, et al. Antisteatotic and antioxidant activities of Thymbra spicata L. extracts in hepatic and endothelial cells as in vitro models of non-alcoholic fatty liver disease. J Ethnopharmacol 2019; 239: 111919. 
  21. Tamaddonfard E, Hamzeh-Gooshchi N. Effect of crocin on the morphine-induced antinociception in the formalin test in rats. Phytother Res 2010; 24: 410-3. 
  22. Dubuisson D, Dennis SG. The formalin test: a quantitative study of the analgesic effects of morphine, meperidine, and brain stem stimulation in rats and cats. Pain 1977; 4: 161-74. 
  23. Abbott FV, Bonder M. Options for management of acute pain in the rat. Vet Rec 1997; 140: 553-7. 
  24. Koster R, Anderson M, De Beer EJ. Acetic acid for analgesic screening. Fed Proc 1959; 18: 412-7. 
  25. Hishe HZ, Ambech TA, Hiben MG, Fanta BS. Antinociceptive effect of methanol extract of leaves of Senna singueana in mice. J Ethnopharmacol 2018; 217: 49-53. 
  26. Yam MF, Loh YC, Tan CS, Khadijah Adam S, Abdul Manan N, Basir R. General pathways of pain sensation and the major neurotransmitters involved in pain regulation. Int J Mol Sci 2018; 19: 2164. 
  27. Hunskaar S, Hole K. The formalin test in mice: dissociation between inflammatory and non-inflammatory pain. Pain 1987; 30: 103-14. 
  28. Ribeiro RA, Vale ML, Thomazzi SM, Paschoalato AB, Poole S, Ferreira SH, et al. Involvement of resident macrophages and mast cells in the writhing nociceptive response induced by zymosan and acetic acid in mice. Eur J Pharmacol 2000; 387: 111-8. 
  29. Karbab A, Mokhnache K, Ouhida S, Charef N, Djabi F, Arrar L, et al. Anti-inflammatory, analgesic activity, and toxicity of Pituranthos scoparius stem extract: an ethnopharmacological study in rat and mouse models. J Ethnopharmacol 2020; 258: 112936. 
  30. Ferraz CR, Carvalho TT, Manchope MF, Artero NA, Rasquel-Oliveira FS, Fattori V, et al. Therapeutic potential of flavonoids in pain and inflammation: mechanisms of action, pre-clinical and clinical data, and pharmaceutical development. Molecules 2020; 25: 762. 
  31. Bagdas D, Ozboluk HY, Cinkilic N, Gurun MS. Antinociceptive effect of chlorogenic acid in rats with painful diabetic neuropathy. J Med Food 2014; 17: 730-2. 
  32. dos Santos MD, Almeida MC, Lopes NP, de Souza GE. Evaluation of the anti-inflammatory, analgesic and antipyretic activities of the natural polyphenol chlorogenic acid. Biol Pharm Bull 2006; 29: 2236-40. 
  33. Shan J, Fu J, Zhao Z, Kong X, Huang H, Luo L, et al. Chlorogenic acid inhibits lipopolysaccharide-induced cyclooxygenase-2 expression in RAW264.7 cells through suppressing NF-kappaB and JNK/AP-1 activation. Int Immunopharmacol 2009; 9: 1042-8. 
  34. Pinheiro MM, Boylan F, Fernandes PD. Antinociceptive effect of the Orbignya speciosa Mart. (Babassu) leaves: evidence for the involvement of apigenin. Life Sci 2012; 91: 293-300. 
  35. Aziz N, Kim MY, Cho JY. Anti-inflammatory effects of luteolin: a review of in vitro, in vivo, and in silico studies. J Ethnopharmacol 2018; 225: 342-58. 
  36. Mino J, Acevedo C, Moscatelli V, Ferraro G, Hnatyszyn O. Antinociceptive effect of the aqueous extract of Balbisia calycina. J Ethnopharmacol 2002; 79: 179-82. 
  37. Filho AW, Filho VC, Olinger L, de Souza MM. Quercetin: further investigation of its antinociceptive properties and mechanisms of action. Arch Pharm Res 2008; 31: 713-21. 
  38. Toker G, Kupeli E, Memisoglu M, Yesilada E. Flavonoids with antinociceptive and anti-inflammatory activities from the leaves of Tilia argentea (silver linden). J Ethnopharmacol 2004; 95: 393-7. 
  39. Yousofvand N, Moloodi B. An overview of the effect of medicinal herbs on pain. Phytother Res 2023; 37: 1057-81. 
  40. Bodnar RJ. Endogenous opiates and behavior: 2018. Peptides 2020; 132: 170348. 
  41. Eisenach JC. Muscarinic-mediated analgesia. Life Sci 1999; 64: 549-54. 
  42. Naser PV, Kuner R. Molecular, cellular and circuit basis of cholinergic modulation of pain. Neuroscience 2018; 387: 135-48. 
  43. Goudet C, Magnaghi V, Landry M, Nagy F, Gereau RW 4th, Pin JP. Metabotropic receptors for glutamate and GABA in pain. Brain Res Rev 2009; 60: 43-56. 
  44. Mahdian Dehkordi F, Kaboutari J, Zendehdel M, Javdani M. The antinociceptive effect of artemisinin on the inflammatory pain and role of GABAergic and opioidergic systems. Korean J Pain 2019; 32: 160-7. 
  45. Hara K, Haranishi Y, Kataoka K, Takahashi Y, Terada T, Nakamura M, et al. Chlorogenic acid administered intrathecally alleviates mechanical and cold hyperalgesia in a rat neuropathic pain model. Eur J Pharmacol 2014; 723: 459-64. 
  46. Obara I, Telezhkin V, Alrashdi I, Chazot PL. Histamine, histamine receptors, and neuropathic pain relief. Br J Pharmacol 2020; 177: 580-99. 
  47. Li P, Zhuo M. Cholinergic, noradrenergic, and serotonergic inhibition of fast synaptic transmission in spinal lumbar dorsal horn of rat. Brain Res Bull 2001; 54: 639-47. 
  48. Martinello K, Sucapane A, Fucile S. 5-HT3 receptors in rat dorsal root ganglion neurons: Ca2+ entry and modulation of neurotransmitter release. Life (Basel) 2022; 12: 1178.