Peganum harmala extract delayed the lethal effect of viper snake Echis carinatus venom in mice

Document Type : Research Article

Authors

Department of Basic Sciences, Faculty of Veterinary Medicine, Ferdowsi University of Mashhad, Mashhad, Iran.

10.22067/ijvst.2025.91424.1454

Abstract

This study evaluated possible antagonistic effects of Peganum harmala against the lethal effect of E. carinatus venom. Seventy-two albino mice were divided into 12 equal groups in 6 experimental protocols. In protocol I, Group A (control) treated with venom. They died after 80 min averagely. In protocol II, Groups B1 and B2 were treated with 15 and 30 mg/kg of P. harmala, respectively and 10 mg/kg venom simultaneously. Their survival time increased to 232 and 210 min respectively. In protocol III, groups C1 and C2 were treated with 10 mg/kg venom and after 15 min received P. harmala at 15 and 30 mg/kg respectively. Their time to death was increased to 246 and 220 min respectively.
In protocol IV, groups D1 and D2, treated with pre-incubated of venom with P. harmala (30 min) at the previous doses. Their survival time increased to 211 and 195 min respectively. In protocol V groups E1 and E2 received only P. harmala extract (IP) at 15 and 30 mg/kg respectively. In protocol VI, groups F1, F2, and F3 received only P. harmala extract (orally) at doses of 15, 30, and 60 mg/kg respectively, they remained alive. Peganum harmala significantly (p < 0.05) increased animal survival time thus, has an antagonistic effect against lethality effect of Echis carinatus venom, make it a possible antivenom candidate for further investigation.

Keywords

Main Subjects


1.    Gutiérrez JM, Calvete JJ, Habib AG, Harrison RA, Williams DJ, Warrell DA. 2017. Snakebite envenoming. Nat Rev Dis Primers, 3: 1-21. Doi:10.1038/nrdp.2017.63.
2.    World Health Organization. 2019. Snakebite Envenoming: A Strategy for Prevention and Control. World Health Organization, Geneva. 
3.    Latifi, M. 2010. The Snakes of Iran. Published by Environment Protection organization, Tehran, 2010. 478 pp. (in Persian, with Latin index).
4.    Yamada D, Sekiya F, Morita T. 1996. Isolation and characterization of Carinactivase, a novel prothrombin activator in Echis carinatus venom with a unique catalytic mechanism, J Biol Chem, 271: 5200-5207.
5.    Warrell DA, Davidson NM, Greenwood BM, Ormerod LD, Pope HM, et al. 1977. Poisoning by bites of Saw-scaled viper or carpet viper (Echiscarinatus) in Nigeria, Q J Med, 46: 33-62.
6.    Dehghani R, Fathi B, Shahi MP, Jazayeri M. 2014. Ten years of snakebites in Iran. Toxicon, 90: 291-298. Doi:10.1016/j.toxicon.2014.08.063.
7.    de Silva HA, Ryan NM, de Silva HJ. 2016. Adverse reactions to snake antivenom, and their prevention and treatment. Brit J Clin Pharm, 81:446-452. Doi:10.1111/bcp.12739.
8.    Lalloo DG, Theakston RD. 2003. Snake antivenoms. J Toxicol Clin Toxicol, 41: 277-290. Doi: 10.1081/clt-120021113.
9.    Habib AG, Brown NI. 2018. The snakebite problem and antivenom crisis from a health-economic perspective. Toxicon. 150: 115-123. Doi: 10.1016/j.toxicon.2018.05.009.
10.     Dey A, De JN. 2011. Traditional use of plants against snakebite in Indian subcontinent: a review of the recent literature. Afr J Tradit Complement Altern Med, 9: 153-174. Doi:10.4314/ajtcam.v9i1.20.
11.     Shirwaikar A, Rajendran K, Bodla R, Kumar CD. 2004. Neutralization potential of Viper russelli russelli (Russell’s viper) venom by ethanol leaf extract of Acalypha indica. J Ethnopharmacol, 94: 267-273. Doi:10.1016/j.jep.2004.05.010.
12.     Rahman R, Faiz MA, Selim S, Rahman B, Basher A, Jones A, d'Este C, Hossain M, Islam Z, Ahmed H, Milton AH. 2010. Annual incidence of snake bite in rural bangladesh. PLoS Negl Trop Dis. 10: e860. Doi:10.1371/journal.pntd.0000860. 
13.     Soares AM, Ticli FK, Marcussi S, Lourenço MV, Januário AH, Sampaio SV, Giglio JR, Lomonte B, Pereira PS. 2005. Medicinal plants with inhibitory properties against snake venoms. Curr Med Chem, 22:2625-2641. Doi:10.2174/092986705774370655. 
14.     Chandrashekara KT, Nagaraju S, Nandini SU, Basavaiah K, Kemparaju K. 2009. Neutralization of local and systemic toxicity of Daboia russelii venom by Morus albaplant leaf extract. Phytother Res, 23: 1082–1087. Doi:10.1002/ptr.2735.
15.     Lizano S, Domont G, Perales J. 2003. Natural phospholipase A (2) myotoxin inhibitor proteins from snakes, mammals and plants. Toxicon, 42: 963-977. Doi:10.1016/j.toxicon.2003.11.007.
16.     Girish K, Mohanakumari HP, Nagaraju S, Vishwanath B, Kemparaju K. 2004. Hyaluronidase and protease activities from Indian snake venoms: neutralization by Mimosa pudica root extract. Fitoterapia, 75: 378–380. Doi:10.1016/j.fitote.2004.01.006.
17.     Nirmal N, Praba GO, Velmurugan D. 2008. Modeling studies on phospholipase A2-inhibitor complexes. Indian J Biochem Biophys, 45: 256-262.
18.     Vineetha MS, Bhavya J1, Sunil SM. 2019. Inhibition of pharmacological and toxic effects of Echis carinatus venom by Tabernaemontana alternifolia root extrac. Indian J Nat Prod Resour, 10: 48-58.
19.     Owuor BO, Kisangau DP. 2006. Kenyan medicinal plants used as antivenin: a comparison of plant usage. J Ethnobiol Ethnomed, 2: 1–8. Doi:10.1186/1746-4269-2-7.
20.     Sajon SR, Sana S, Rana S. 2017. Anti-venoms for snake bite: a synthetic and traditional drugs review. J Pharmacogn Phytochem, 6: 190–197.
21.     Lamchouri F, Settaf A, Cherrah Y, Zemzami M, Lyoussi B, Zaid A, Atif N, Hassar M. 1999. Antitumour principles from Peganum harmala seeds. Therapie, 54: 753–758.
22.     Asgarpanah J, Ramezanloo F. 2012. Chemistry, pharmacology and medicinal properties of Peganum harmala L. Afr J Pharm Pharmacol, 6: 1573-1580. 
23.    Mahmoudian M, Jalipour H, Dardashti PS. 2002. Toxicity of Peganum harmala: Review and a case report. Iran J Pharmacol Ther, 1:1-4.
24.     Karasawa MMG, Mohan C. Fruits as prospective reserves of bioactive compounds: A Review. 2018. Nat Prod Bioprospect, 8: 335-346.Doi:10.1007/s13659-018-0186-6. 
25.     Sharifi-Rad J, Quispe C, Herrera-Bravo J, Semwal P, Painuli S, Özçelik B et al. 2021. Peganum spp. A Comprehensive Review on Bioactivities and Health-Enhancing Effects and Their Potential for the Formulation of Functional Foods and Pharmaceutical Drugs. Oxid Med Cell Longev, 5900422. Doi: 10.1155/2021/5900422.
26.    Lamchouri F, Settaf A, Cherrah Y, El Hamidi M, Tligui N, Lyoussi B, et al. 2002. Experimental toxicity of Peganum harmala seeds. Annales Pharmaceutiques Françaises, 60: 123-129.
27.     Marcussi S, Sant'Ana CD, Oliveira CZ, Rueda AQ, Menaldo DL, Beleboni RO, Stabeli RG, Giglio JR, Fontes MR, Soares AM. 2007. Snake venom phospholipase A2 inhibitors: medicinal chemistry and therapeutic potential. Curr Top Med Chem, 7: 743-756. Doi:10.2174/156802607780487614.
28.    Teixeira C, Cury Y, Moreira V, Picolo G, Chaves F. 2009. Inflammation induced by Bothrops asper venom. Toxicon, 54: 67-76. Doi:10.1016/j.toxicon.2009.03.019.
29.     Aird SD. 2002. Ophidian envenomation strategies and the role of purines. Toxicon, 40: 335-393. Doi:10.1016/s0041-0101(01)00232-x.
30.     Ushanandini S, Nagaraju S, Harish Kumar K, Vedavathi M, Machiah D K, et al. 2006. The anti-snake venom properties of Tamarindus indica (leguminosae) seed extract, Phytother Res, 20: 851-858. Doi:10.1002/ptr.1951.
31.     de Moura VM, da Silva WCR, Raposo JDA, Freitas-de- Sousa LA, Dos-Santos M C, et al. 2016. The inhibitory potential of the condensed-tannin-rich fraction of Plathymenia reticulata Benth. (Fabaceae) against Bothrops atrox envenomation, J Ethnopharmacol, 183: 136-142. Doi:10.1016/j.jep.2016.02.047.
32.     Meenatchisundaram S, Prajish G P, Subbraj T and Michael A. 2008. Studies on anti-venom activity of Andrographis paniculata and Aristolochia indica plant extracts against Echis carinatus venom, Internet J Toxicol, 6: 1-7.
33.    Miyake A, Yamamoto H, Takebayashi Y, Imai Hm Honda K. 1992. The novel natural product YM-26567-1 [(+)-trans-4-(3-dodecanoyl-2,4,6- trihydroxyphenyl)-7-hydroxy-2-(4-hydroxyphenyl) chroman]: a competitive inhibitor of group II phospholipase A2. Mol Cell Pharmacol, 263; 1302-1307.
34.     Mahadeshwaraswamy Y H, Nagaraju S, Girish K S and Kemparaju K. 2008.  Local tissue destruction and procoagulation properties of Echis carinatus venom: inhibition by Vitis vinifera seed methanol extract. Phytother Res, 22: 963-969. Doi:10.1002/ptr.2462.
35.     Glennon RA, Dukat M, Grella B, Hong S, Costantino L, Teitler M, Smith C, Egan C, Davis K, Mattson MV. 2000. Binding of beta-carbolines and related agents at serotonin (5-HT (2) and 5-HT(1A)), dopamine (D (2)) and benzodiazepine receptors. Drug Alcohol Depend, 60:121-132. Doi:10.1016/s0376-8716(99)00148-9.
36.     Herraiz, T. González, DC. Ancín-Azpilicueta, C. Arán, VJ, Guillén, H. 2010. β-Carboline alkaloids in Peganum harmala and inhibition of human monoamine oxidase (MAO), Food Chem Toxicol, 48: 839–845.Doi:10.1016/j.fct.2009.12.019.
37.     Harris JB. 2009. Neuromuscular junction (NMJ): a target for natural and environmental toxins in humans. Encyclopedia of Neuroscience. Boston: Elesevier Academic Press, 539–549.
38.     Yang Y, Cheng X, Liu W, Chou G, Wang Z, Wang C. 2015. Potent AChE and BChE inhibitors isolated from seeds of Peganum harmala Linn by a bioassay-guided fractionation. J Ethnopharmacol, 68: 279-286. Doi:10.1016/j.jep.2015.03.070.
39.     Soliman AM, Abu-El-Zahab HS, Alswiai GA. 2013. Efficacy evaluation of the protein isolated from Peganum harmala seeds as an antioxidant in liver of rats. Asian Pac J Trop Med, 6: 285–295. Doi:10.1016/s1995-7645(13)60058-9.
 
CAPTCHA Image