Effect of Red Algae ethanolic extract and its possible neural interactions on formalin-induced pain in mice

Subject Areas : Journal of Comparative Pathobiology

مهسا Mahsa ¹ , Amireghbal KhajehRahimi ² , Shahin Hassanpour ³

1 - Graduate student, Faculty of Veterinary Medicine, Science and Research Branch, Islamic Azad University, Tehran, Iran
2 - دانشکده دامپزشکی،دانشگاه آزاد اسلامی واحد علوم و تحقیقات ،تهران ،ایران
3 - Department of Veterinary Medicine, Science and Research Branch, Islamic Azad University, Tehran, Iran

Received: 2021-11-03 Accepted : 2021-11-03 Published : 2020-12-21

Keywords: Red algae, Pain, Serotonergic, GABAergic, Histaminergic, mice,

Abstract :

Due to the side effects of chemical drugs in pain relief, the use of herbal medicines is increasing. Red algae have antioxidant, antibacterial, antifungal, antitumor, and antimicrobial properties. The present study aimed to investigate the effect of Red Algae ethanolic extract and its possible neural interactions on formalin-induced pain in mice. 125 adult male mice allocated in 6 experiments. In the first experiment, mice were injected intraperitoneally with saline, red algae extract (2.5, 5, and 10 mg/kg), and morphine (5 mg/kg). In the second experiment, mice received intraperitoneal injections of saline, red algae extract (10 mg/kg), naloxone (non-selective opioid antagonist, 2 mg/kg), and naloxone + red algae extract. Experiments 4 to 6 were similar to the second experiment but injected with flumazenil (non-selective GABA receptor antagonist, 5 mg/kg), cyproheptadine (non-selective serotonin receptor antagonist, 2 mg/kg), chlorpheniramine (histamine H1receptors antagonist, 20 mg/kg) and cimetidine (histamine H2receptors antagonist, 12.5 mg/kg) were used instead of naloxone. After 30 minutes, subcutaneous injection of formaldehyde was performed on the plantar surface of the right foot, and the time of licking, chewing, and biting (Licking Time) was measured. According to the results, morphine significantly reduced pain time compared to the control group (P<0.05). Red algae extract in a dose-dependent manner reduced pain compared to the control group (P<0.05). Injection of naloxone + red algae extract significantly reduced the analgesic effects of red algae extract compared to the group of red algae extract (P<0.05). Flumazenil + red algae extract significantly reduced the analgesic effects of red algae extract (P<0.05). Injection of cyproheptadine + red algae extract significantly enhanced the analgesic effects of red algae extract (P<0.05). Injection of chlorpheniramine + red algae extract significantly reduced the analgesic effects of red algae extract (P<0.05). The results showed that the analgesic effects of red algae are mediated by opioidergic, serotonergic, GABAergic and histaminergic pathways.

References:

1. Chiu IM, Ribeiro F, Woolf CJ. Pain and infection: pathogen detection by nociceptors. Pain. 2016;157(6):1192.


2. Monteiro VS, Teles FB, Coura CO, Souza RB, de Carvalho Lima CN, da Silva Costa DV, et al. Involvement of the GABAergic system in the anxiolytic effect of sulfated polysaccharides from the red seaweed Gracilaria cornea. Journal of Applied Phycology. 2016;28(3):1997-2004.


3. Fallahzadeh A, Mohammadi S. An investigation of the antinociceptive and anti-inflammatory effects of hydroalcoholic extract of Inula helenium on male rats. Journal of Babol University of Medical Sciences. 2016;18(12):57-63.


4. Zarei M, Mohammadi S, Abolhassani N, ASGARI NM. The antinociceptive effects of hydroalcoholic extract of bryonia dioica in male rats. 2015.


5. Izadpanah E, Nikandam F, Moloudi MR, Hassanzadeh K. Evaluation of the analgesic effect of hydroalcoholic extract of Cinnamomum in rats. Scientific Journal of Kurdistan University of Medical Sciences. 2016;21(4):41-8.


6. Zarei M, Mohammadi S, Shahidi S, Fallahzadeh AR. Effects of Sonchus asper and apigenin-7-glucoside on nociceptive behaviors in mice. Journal of Pharmacy & Pharmacognosy Research. 2017;5(4):227-37.


7. Ghaffari M, Taheri A, Zobeidinezhad M. In vitro Evaluation of Antibacterial Effect of Ethyl Acetate Extract of Red Algae (Gelidiella acerosa) on Some Gram-positive and Gram-negative Bacteria. Journal of Rafsanjan University of Medical Sciences. 2016;15(3):209-22.


8. Ma J, Yu H, Liu J, Chen Y, Wang Q, Xiang L. Curcumin promotes nerve regeneration and functional recovery after sciatic nerve crush injury in diabetic rats. Neuroscience letters. 2016;610:139-43.


9. Omar H, Shiekh H, Gumgumjee N, El-Kazan M, El-Gendy A. Antibacterial activity of extracts of marine algae from the Red Sea of Jeddah, Saudi Arabia. African Journal of Biotechnology. 2012;11(71):13576-85.


10. Shafaghi M, Salehzadeh A, Moshfegh A. Anticancer effects of Laurencia caspica extract on breast cancer T47D cell line. Aquatics Physiology and Biotechnology. 2016;4(1):69-83.


11. Asmawati A, Hasyim R, Lianingsih A, Ariani D. The difference of anti-inflammatory effect of brown algae extract panida sp. and sargassum sp that is derived from Punaga beach, South Sulawesi. J Dentomaxillofac Sci. 2016;1:116-9.


12. Labuz D, Celik MÖ, Zimmer A, Machelska H. Distinct roles of exogenous opioid agonists and endogenous opioid peptides in the peripheral control of neuropathy-triggered heat pain. Scientific reports. 2016;6:32799.


13. Hunskaar S, Hole K. The formalin test in mice: dissociation between inflammatory and non-inflammatory pain. Pain. 1987;30(1):103-14.


14. Abdallah H, Asaad G, Arbid M, Abdel-Sattar E. Anti-inflammatory, Antinociceptive, Antipyretic and Gastroprotective Effects of Calligonum comosum in Rats and Mice. International Journal of Toxicological and Pharmacological Research. 2014;6(2):26-33.


15. Shahin H, Hadis R, Razavi SM. Anti-nociceptive and antioxidant activity of Betaine on Formalin-and Writhing tests induced pain in mice. Behavioural Brain Research. 2020:112699.


16. Hong DD, Hien HM, Anh HTL. Studies on the analgesic and anti-inflammatory activities of Sargassum swartzii (Turner) C. Agardh (Phaeophyta) and Ulva reticulata Forsskal (Chlorophyta) in experiment animal models. African Journal of Biotechnology. 2011;10(12):2308-13.


17. Chaves LdS, Nicolau LAD, Silva RO, Barros FCN, Freitas ALP, Aragão KS, et al. Antiinflammatory and antinociceptive effects in mice of a sulfated polysaccharide fraction extracted from the marine red algae Gracilaria caudata. Immunopharmacology and immunotoxicology. 2013;35(1):93-100.


18. Aragão GF, Nonato DTT, da Ponte EL, Sales JR, Alencar DB, Sampaio SS, et al. Protective effects of ethanolic extract from the red algae Amansia multifida on experimental inflammation, nociception and seizure experimental models. Acta Scientiarum Biological Sciences. 2016;38(4):465-71.


19. García Delgado N, Frías Vázquez AI, Cabrera Sánchez H, Soto del Valle RM, Sierra Gómez Y, Suárez Alfonso AM. Anti-inflammatory and antinociceptive activities of methanolic extract from red seaweed Dichotomaria obtusata. Brazilian Journal of Pharmaceutical Sciences. 2013;49(1):65-74.


20. Vázquez AIF, Sánchez CMD, Delgado NG, Alfonso AMS, Ortega YS, Sánchez HC. Anti-inflammatory and analgesic activities of red seaweed Dichotomaria obtusata. Brazilian Journal of Pharmaceutical Sciences. 2011;47(1):111-8.


21. Zhang S-D, Qin J-J, Jin H-Z, Yin Y-H, Li H-L, Yang X-W, et al. Sesquiterpenoids from Inula racemosa Hook. f. inhibit nitric oxide production. Planta medica. 2012;78(02):166-71.


22. Mojtahedin A, Gholizadeh NikPey M, Hajighahramani S. Interaction of the effect of histaminergic system and aqueous extract of Barberry on formalin-induced pain in male rats. Journal od Animal Enviroment.9(4):85-94.


23. Mojtahedin A. Effects of cholinergic system in antinociception induced by H‐1 and H‐2 receptor antagonists on somatic pain in rats. Int J Med Res Health Sci. 2016;5:378-83.


24. Salimi S, Tamaddonfard E. Microinjection of histamine and its H3 receptor agonist and antagonist into the agranular insular cortex influence sensory and affective components of neuropathic pain in rats. European journal of pharmacology. 2019;857:172450.


25. Erfanparast A, Tamaddonfard E, Henareh-Chareh F, editors. Central H2 histaminergic and alpha-2 adrenergic receptors involvement in crocetin-induced antinociception in orofacial formalin pain in rats. Veterinary Research Forum; 2020: Faculty of Veterinary Medicine, Urmia University, Urmia, Iran.


26. Al-Hariri MT, Abualait TS. Effects of Green Brazilian Propolis Alcohol Extract on Nociceptive Pain Models in Rats. Plants. 2020;9(9):1102.


27. Wang Z-J, Heinbockel T. Essential oils and their constituents targeting the gabaergic system and sodium channels as treatment of neurological diseases. Molecules. 2018;23(5):1061.