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Evaluation of the antinociceptive activities of natural propolis extract derived from stingless bee Trigona thoracica in mice

  • Received : 2023.11.09
  • Accepted : 2024.01.11
  • Published : 2024.04.01

Abstract

Background: Stingless bee propolis is a popular traditional folk medicine and has been employed since ancient times. This study aimed to evaluate the antinociceptive activities of the chemical constituents of aqueous propolis extract (APE) collected by Trigona thoracica in a nociceptive model in mice. Methods: The identification of chemical constituents of APE was performed using high-performance liquid chromatography (HPLC). Ninety-six male Swiss mice were administered APE (400 mg/kg, 1,000 mg/kg, and 2,000 mg/kg) before developing nociceptive pain models. Then, the antinociceptive properties of each APE dose were evaluated in acetic acid-induced abdominal constriction, hot plate test, and formalin-induced paw licking test. Administration of normal saline, acetylsalicylic acid (ASA, 100 mg/kg, orally), and morphine (5 mg/kg, intraperitoneally) were used for the experiments. Results: HPLC revealed that the APE from Trigona thoracica contained p-coumaric acid (R2 = 0.999) and caffeic acid (R2 = 0.998). Although all APE dosages showed inhibition of acetic acid-induced abdominal constriction, only 2,000 mg/kg was comparable to the result of ASA (68.7% vs. 73.3%, respectively). In the hot plate test, only 2,000 mg/kg of APE increased the latency time significantly compared to the control. In the formalin test, the durations of paw licking were significantly reduced at early and late phases in all APE groups with a decrease from 45.1% to 53.3%. Conclusions: APE from Trigona thoracica, containing p-coumaric acid and caffeic acid, exhibited antinociceptive effects, which supports its potential use in targeting the prevention or reversal of central and peripheral sensitization that may produce clinical pain conditions.

Keywords

Acknowledgement

The authors thank the Faculty of Medicine, Universiti Sultan Zainal Abidin (UniSZA) for providing the facilities.

References

  1. Heard TA. The role of stingless bees in crop pollination. Annu Rev Entomol 1999; 44: 183-206.  https://doi.org/10.1146/annurev.ento.44.1.183
  2. Ruttner F. Stingless bees (Meliponinae). In: Biogeography and taxonomy of honeybees. Edited by Ruttner F. Springer, Berlin, Heidelberg. 1988, pp 13-9. 
  3. Kelly N, Farisya MSN, Kumara TK, Marcela P. Species diversity and external nest characteristics of stingless bees in meliponiculture. Pertanika J Trop Agric Sci 2014; 37: 293-8. 
  4. Campos JF, dos Santos UP, Macorini LF, de Melo AM, Balestieri JB, Paredes-Gamero EJ, et al. Antimicrobial, antioxidant and cytotoxic activities of propolis from Melipona orbignyi (Hymenoptera, Apidae). Food Chem Toxicol 2014; 65: 374-80.  https://doi.org/10.1016/j.fct.2014.01.008
  5. Campos JF, Dos Santos UP, da Rocha Pdos S, Damiao MJ, Balestieri JB, Cardoso CA, et al. Antimicrobial, antioxidant, anti-inflammatory, and cytotoxic activities of propolis from the stingless bee Tetragonisca fiebrigi (Jatai). Evid Based Complement Alternat Med 2015; 2015: 296186. 
  6. Torres AR, Sandjo LP, Friedemann MT, Tomazzoli MM, Maraschin M, Mello CF, et al. Chemical characterization, antioxidant and antimicrobial activity of propolis obtained from Melipona quadrifasciata quadrifasciata and Tetragonisca angustula stingless bees. Braz J Med Biol Res 2018; 51: e7118. 
  7. Machado JL, Assuncao AK, da Silva MC, Dos Reis AS, Costa GC, Arruda Dde S, et al. Brazilian green propolis: anti-inflammatory property by an immunomodulatory activity. Evid Based Complement Alternat Med 2012; 2012: 157652. 
  8. Touzani S, Embaslat W, Imtara H, Kmail A, Kadan S, Zaid H, et al. In vitro evaluation of the potential use of propolis as a multitarget therapeutic product: physicochemical properties, chemical composition, and immunomodulatory, antibacterial, and anticancer properties. Biomed Res Int 2019; 2019: 4836378. 
  9. Ismail TNNT, Sulaiman SA, Ponnuraj KT, Man CN, Hassan NB. Chemical constituents of Malaysian Apis mellifera propolis. Sains Malaysiana 2018; 47: 117-22.  https://doi.org/10.17576/jsm-2018-4701-14
  10. Mohamed WAS, Ismail NZ, Omar EA, Abdul Samad N, Adam SK, Mohamad S. GC-MS evaluation, antioxidant content, and cytotoxic activity of propolis extract from Peninsular Malaysian stingless bees, Tetrigona Apicalis. Evid Based Complement Alternat Med 2020; 2020: 8895262. 
  11. Ibrahim N, Mohd Niza NFS, Mohd Rodi MM, Zakaria AJ, Ismail Z, Mohd KS. Chemical and biological analyses of Malaysian stingless bee propolis extracts. MJAS 2016; 20: 413-22.  https://doi.org/10.17576/mjas-2016-2002-26
  12. Blakemore PR, White JD. Morphine, the Proteus of organic molecules. Chem Commun 2002; 2: 1159-68.  https://doi.org/10.1039/b111551k
  13. Allison MC, Howatson AG, Torrance CJ, Lee FD, Russell RI. Gastrointestinal damage associated with the use of nonsteroidal antiinflammatory drugs. N Engl J Med 1992; 327: 749-54.  https://doi.org/10.1056/NEJM199209103271101
  14. Brodkiewicz Y, Marcinkevicius K, Reynoso M, Salomon V, Maldonado L, Vera N. Studies of the biological and therapeutic effects of Argentine stingless bee propolis. JDDT 2018; 8: 382-92. 
  15. Al-Hariri MT, Abualait TS. Effects of green Brazilian propolis alcohol extract on nociceptive pain models in rats. Plants (Basel) 2020; 9: 1102. 
  16. Sun L, Liao L, Wang B. Potential antinociceptive effects of Chinese propolis and identification on its active compounds. J Immunol Res 2018; 2018: 5429543. 
  17. Tiveron AP, Rosalen PL, Franchin M, Lacerda RC, Bueno-Silva B, Benso B, et al. Chemical characterization and antioxidant, antimicrobial, and antiinflammatory activities of South Brazilian organic propolis. PLoS One 2016; 11: e0165588. 
  18. Lima Cavendish R, de Souza Santos J, Belo Neto R, Oliveira Paixao A, Valeria Oliveira J, Divino de Araujo E, et al. Antinociceptive and anti-inflammatory effects of Brazilian red propolis extract and formononetin in rodents. J Ethnopharmacol 2015; 173: 127-33.  https://doi.org/10.1016/j.jep.2015.07.022
  19. Aziz MSA, Giribabu N, Rao PV, Salleh N. Pancreatoprotective effects of Geniotrigona thoracica stingless bee honey in streptozotocin-nicotinamide-induced male diabetic rats. Biomed Pharmacother 2017; 89: 135-45.  https://doi.org/10.1016/j.biopha.2017.02.026
  20. Abdullah NA, Zullkiflee N, Zaini SNZ, Taha H, Hashim F, Usman A. Phytochemicals, mineral contents, antioxidants, and antimicrobial activities of propolis produced by Brunei stingless bees Geniotrigona thoracica, Heterotrigona itama, and Tetrigona binghami. Saudi J Biol Sci 2020; 27: 2902-11.  https://doi.org/10.1016/j.sjbs.2020.09.014
  21. Colucci M, Maione F, Bonito MC, Piscopo A, Di Giannuario A, Pieretti S. New insights of dimethyl sulphoxide effects (DMSO) on experimental in vivo models of nociception and inflammation. Pharmacol Res 2008; 57: 419-25.  https://doi.org/10.1016/j.phrs.2008.04.004
  22. Mohd Salim NH, Azam Omar E, Wan Omar WA, Mohamed R. Chemical constituents and antioxidant activity of ethanolic extract of propolis from Malaysian stingless bee Geniotrigona thoracica species. Res J Pharm Biol Chem Sci 2018; 9: 646-51. 
  23. Sani MH, Zakaria ZA, Balan T, Teh LK, Salleh MZ. Antinociceptive activity of methanol extract of Muntingia calabura leaves and the mechanisms of action involved. Evid Based Complement Alternat Med 2012; 2012: 890361. 
  24. Hajhashemi V, Khodarahmi G, Asadi P, Rajabi H. Evaluation of the antinociceptive effects of a selection of triazine derivatives in mice. Korean J Pain 2022; 35: 440-6.  https://doi.org/10.3344/kjp.2022.35.4.440
  25. Muhamad Suhaini NA, Pauzi MF, Juhari SN, Mohd KS, Abu Bakar NA. In vivo toxicity study on the effects of aqueous propolis extract from Malaysian stingless bee (Geniotrigona thoracica) in mice. Malays Appl Biol 2023; 52: 61-9. 
  26. Ramos AFN, Miranda JL. Propolis: a review of its anti-inflammatory and healing actions. J Venom Anim Toxins incl Trop Dis 2007; 13: 697-710.  https://doi.org/10.1590/S1678-91992007000400002
  27. Zhu W, Chen M, Shou Q, Li Y, Hu F. Biological activities of Chinese propolis and Brazilian propolis on streptozotocin-induced type 1 diabetes mellitus in rats. Evid Based Complement Alternat Med 2011; 2011: 468529. 
  28. Olczyk P, Ramos P, Komosinska-Vassev K, Stojko J, Pilawa B. Positive effect of propolis on free radicals in burn wounds. Evid Based Complement Alternat Med 2013; 2013: 356737. 
  29. Kasote DM, Pawar MV, Gundu SS, Bhatia R, Nandre VS, Jagtap SD, et al. Chemical profiling, antioxidant, and antimicrobial activities of Indian stingless bees propolis samples. J Apic Res 2019; 58: 617-25.  https://doi.org/10.1080/00218839.2019.1584960
  30. Bankova VS, Trusheva B, Popova M. Propolis extraction methods: a review. J Apic Res 2021; 60: 734-43.  https://doi.org/10.1080/00218839.2021.1901426
  31. Park SH, Sim YB, Kim SM, Lee JK, Jung JS, Suh HW. The effect of caffeic acid on the antinociception and mechanisms in mouse. J Appl Biol Chem 2011; 54: 177-82. 
  32. Vogel HG. Drug discovery and evaluation: pharmacological assays. Springer Berlin, Heidelberg. 2007. 
  33. Le Bars D, Gozariu M, Cadden SW. Animal models of nociception. Pharmacol Rev 2001; 53: 597-652. 
  34. Akindele AJ, Ibe IF, Adeyemi OO. Analgesic and antipyretic activities of Drymaria cordata (Linn.) Willd (Caryophyllaceae) extract. Afr J Tradit Complement Altern Med 2011; 9: 25-35. 
  35. Zakaria ZA, Kumar GH, Mat Jais AM, Sulaiman MR, Somchit MN. Antinociceptive, antiinflammatory and antipyretic properties of Channa striatus fillet aqueous and lipid-based extracts in rats. Methods Find Exp Clin Pharmacol 2008; 30: 355-62.  https://doi.org/10.1358/mf.2008.30.5.1236620
  36. Franchin M, da Cunha MG, Denny C, Napimoga MH, Cunha TM, Koo H, et al. Geopropolis from Melipona scutellaris decreases the mechanical inflammatory hypernociception by inhibiting the production of IL-1β and TNF-α. J Ethnopharmacol 2012; 143: 709-15.  https://doi.org/10.1016/j.jep.2012.07.040
  37. McDonald J, Lambert DG. Opioid receptors. Cont Educ Anaesth Crit Care Pain 2005; 5: 22-5.  https://doi.org/10.1093/bjaceaccp/mki004
  38. Vidyalakshmi K, Kamalakannan P, Viswanathan S, Ramaswamy S. Antinociceptive effect of certain dihydroxy flavones in mice. Pharmacol Biochem Behav 2010; 96: 1-6.  https://doi.org/10.1016/j.pbb.2010.03.010
  39. Mountassir M, Chaib S, Selami Y, Khalki H, Ouachrif A, Moubtakir S, et al. Antinociceptive activity and acute toxicity of Moroccan black propolis. IJERT 2014; 3: 2393-7. 
  40. Tjolsen A, Berge OG, Hunskaar S, Rosland JH, Hole K. The formalin test: an evaluation of the method. Pain 1992; 51: 5-17.  https://doi.org/10.1016/0304-3959(92)90003-T
  41. Hunskaar S, Hole K. The formalin test in mice: dissociation between inflammatory and non-inflammatory pain. Pain 1987; 30: 103-14.  https://doi.org/10.1016/0304-3959(87)90088-1
  42. Shibata M, Ohkubo T, Takahashi H, Inoki R. Modified formalin test: characteristic biphasic pain response. Pain 1989; 38: 347-52. https://doi.org/10.1016/0304-3959(89)90222-4