Analgesic effect of Persian Gulf Conus textile venom

Document Type : Original Article


1 Department of Marine Biology, Science and Research Branch, Islamic Azad University (IAU), Tehran, Iran

2 Biotechnology Research Center, Department of Medical Biotechnology, Venom and Biotherapeutics Molecules Lab, Pasteur Institute of Iran, Tehran Iran


Objective(s):Cone snails are estimated to consist of up to 700 species. The venom of these snails has yielded a rich source of novel peptides. This study was aimed to study the analgesic effect of Persian Gulf Conus textile and its comparison with morphine in mouse model.
Materials and Methods: Samples were collected in Larak Island. The venom ducts were Isolated and kept on ice then homogenized. The mixture centrifuged at 10000 × g for 20 min. Supernatant was considered as extracted venom. The protein profile of venom determined using 15% sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Venom was administered intraperitoneally (IP) to evaluate the LD50 in Swiss albino mice. Different concentrations of Conus textile venom were injected intrathecally to mice to evaluate their analgesic effect in comparison to morphine. Injection was carried out between the L5 and L6 vertebrae. Differences between groups in the first and second phase were tested with Two-Way analysis of variance (ANOVA).
Results: SDS-PAGE indicated 12 bands ranged between 6 and 180 KDa. Finally, ten ng of Conus crude venom showed the best analgesic activity in formalin test. No death observed up to 100 mg/kg. Analgesic activity of crude venom was more significant (P<0.05) in acute pain than inflammatory pain. The analgesic effect of 10 ng Conus venom was the same as morphine for reduction of inflammatory pain (P=0.27).
Conclusion: The venom of Persian Gulf Conus textile contains an analgesic component for reliving of acute pain which can lead to find an analgesic drug.


1. Olivera BM, Gray WR, Zeikus R, McIntosh JM, Varga J, Rivier J, et al. Peptide neurotoxins from fish-huntingcone snails. Science 1985; 230:1338–1343.
2. Olivera BM, Rivier J, Scott JK, Hillyard DR, Cruz LJ. Conotoxins. J Biol Chem 1991; 33:22067- 22070. 
3. Terlau H, Olivera B. Conus venoms: a rich source of novel ion channel-targeted peptides. Physiol Rev 2004; 84:41-68.
4. Han TS, Teichert RW, Olivera BM, Bulaj G. Conus Venoms-A rich source of peptide-based therapeutics. Curr Pharm Des 2008; 14:2462–2479.
5. Lee S, Kim Y, Back SK, Choi HW, Lee JY, Jung HH, et al. Analgesic effect of highly reversible ω- conotoxin FVIA on N-type Ca+2 channels. Mol Pain 2010; 6:97. 
6. Olivera BM, Walker C, Cartier GE, Hooper D, Santos AD, Schoenfeld R, et al.  Speciation of cone snails and interspecific hyperdivergence of their venom peptides, evolutionary significance of introns. Ann N Y Acad Sci 1999; 870:223-237.
7. Becker S, Terlau H. Toxins from cone snails: properties, applications and biotechnological production. Appl Microbiol Biotechnol 2008; 79: 1-9.
8. Marsh H. Preliminary studies of venoms of some vermivorous Conidae. Toxicon 1970; 8: 271–277.
9. Ramilo CA, Zafaralla GC, Nadasdi L, Hammerland LG, Yoshikami D, Gray WR, et al. Novel a- and v-conotoxins from Conusstriatus venom. Biochemistry 1992; 31:9919-9926.
10. Clark C, Olivera BM, Cruz LJ. A toxin from the venom of the marine snail Conusgeoghraphus which acts on the vertebrate central nervous system. Toxicon 1981; 19:691-699.
11. Tayo LL, Lu B, Cruz LJ, Yates JR 3rd. Proteomic analysis provides insights on venom processing in Conus textile. J Proteome Res 2010; 9:2292-2301.
12. Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 1970; 227: 680–685.
13. Amrollahi Byoki E, Zare Mirakabadi A. Partial Purification and Characterization of Anticoagulant Factor from the Snake (Echiscarinatus) Venom. Iran J Basic Med Sci 2013; 16:1139-1144.
14. Moallem SA, Imenshahidi M, Shahini N, Javan AR, Karimi M, Alibolandi M, et al. Synthesis, Anti-Inflammatory and Anti- Nociceptive Activities and Cytotoxic Effect of Novel Thiazolidin-4-ones Derivatives as Selective Cyclooxygenase (COX-2) Inhibitors. Iran J Basic Med Sci 2013; 16:1238-1244.
15. Hunskaar S, Fasmer OB, Hole K. Formalin test in mice, a useful technique for evaluating analgesics. J Neurosci Methods 1985; 14:69-76.
16. Cearley CN, Wolfe JH. A single injection of an adeno-associated virus vector into nuclei with divergent connections results in widespread vector distribution in the brain and global correction of a neurogenetic disease. J Neurosci 2007; 27:9928–9940.
17. Pahlavan Y, Sepehri G, Sheibani V, Afarinesh khaki M, Gojazadeh M, Pahlavan B, et al. Study the antinociceptive effect of intracerebroventricular injection of aqueous extract of origanumvulgare leaves in rat: Possible Involvement of Opioid System. Iran J Basic Med Sci 2013; 16:1110-1113.
18. Endean R, Rudkin C. Studies of the venoms of some Conidae. Toxicon 1963; 1:49-64.
19. Endean R, Rudkin C. Further studies of the venom of Conidae. Toxicon 1965; 69: 225–249.
20. Wen L, Yang SH, Zhou W, Zhang Y, Huang P. New conotoxin so-3 targeting N-Type voltage-sensitive calcium channels. Mar Drugs 2006; 4:215-227.
21. Olivera BM, Teichert RW. Diversity of the Neurotoxic Conus peptides, A Model for Concerted Pharmacological Discovery. Mol Interv 2007; 7:251-260.
22. Elliger CA, Richmond TA, Lebaric ZN, Pierce NT, Sweedler JV, Gilly WF. Diversity of conotoxin types from Conuscalifornicus reflects a diversity of prey types and a novel evolutionary history. Toxicon 2011; 57:311–322.
23. Baby J, Sheeja SR, Jeevitha M, Ajiha S, Jini D. Conotoxins: a potential natural therapeutic for pain relief. Int J Pharm Pharmacol Sci 2011; 3:1-5.
24. Stix G. A toxin against pain. Sci Am 2005; 292:88-93.
25. Rajendra W, Armugam A, Jeyaseelan K. Toxins in anti-nociception and anti-inflammation. Toxicon 2004; 44:1-17.
26. Gray WR, Luque A, Olivera BM, Barrett J, Cruz LJ. Peptide toxins from Conusgeographus venom. J Biol Chem 1981; 256:4734-4740.
27. Buczek O, Wei D, Babon JJ, Yang X, Fiedler B, Chen P, et al. Structure and sodium channel activity of an excitatory I(1)-superfamily conotoxin. Biochemistry 2007; 46:9929–9940.
28. Kauferstein S, Huys I, Kuch U, Melaun C, Tytgat J, Mebs D. Novel conopeptides of the I-superfamily occur in several clades of cone snails. Toxicon 2004; 44: 539–548.
29. Kobayashi J, Ohizumi Y, Nakamura H, Hirata Y. Pharmacological study on the venom of the marine snail conus textile. Toxicon 1981; 19:757-762.
30. Buenaflor HG, Mendoza E, Cruz LJ. Studies of the biochemical nature of Conus magus venom. Philipp J Biol 1981; 10:220-230.
31. Woolf CJ, Moving from symptom control toward mechanism-specific pharmacologic management. Ann Intern Med 2004; 140:441-451.
32. Tiwari G, Tiwari R, Sriwastawa B, Bhati L, Pandey S, Pandey P, et al. Drug delivery systems: An updated review. Int J Pharm Investig 2012; 2:2–11.
33. Dey NS, Majumdar S, Rao M. Multiparticulate drug delivery systems for controlled release. Tropical Journal of Pharmaceutical Research 2008; 7:1067-1075.
34. Rafi Shaik M, Korsapati M, Panati D. Polymers in controlled drug delivery systems. Int J Pharm Sci 2012; 2:112-116.
35. Garg T, Bilandi A, Kapoor B, Kumar S. Current status and future directions of new drug delivery technologies. International research journal of pharmacy 2011; 2:61–68.