ANXIOLYTIC AND ANTIDEPRESSANT ACTIVITY OF CARICA PAPAYA SEEDS AND LEAVES EXTRACTS IN MICE

Main Article Content

Safila Naveed
Ayesha Khan
Muhammad Ulusyar Khan
Tajala Aman
Abeer Adil
Fatima Qamar
Halima Sadia
Mehwish Khan
Wajeeha Muzafar

Keywords

Anti-anxiety, anti-depressant, C. papaya, Light and Dark model and Stationary rod

Abstract

Context: Carica papaya (Caricaceae) originally belongs to tropical region of America. It is an edible and juicy fruit. Seeds are present inside the fruit. All the parts of the tree especially fruits, seeds and leaves have many medicinal properties. C. Papaya fruit acts as anti-diabetic, for liver disease, its seeds act as hypoglycemic, hypolipidimic, cardioprotective, contraceptive etc. In Ethiopian traditional medicine, C. papaya has been used to treat a variety of ailments, including stress.


Objective: The purpose of the present study was to investigate the anxiolytic effects of various extracts of the seeds and leaves of C. papaya.


Materials and methods: Fresh ethanolic and methanolic extract of seeds and leaves of C. papayawere prepared and administered to mice and rats for anxiolytic activity such as Cage crossing, Head dip, Stationary rod, Open field and Light and Dark on mice and Forced swimming test on rats.


Results: Both the extracts of C.papaya decreased anxiety, fear related behavior in mice and rats. We observe that the number of cage crossed decrease which indicates decrease in anxiety, also the number of head dips gradually decrease which shows anxiolytic effect. The investigation within the peripheral square crosses was diminished showing the antidepressant action. For both the extracts, two-way ANOVA data analysis produces pretty significant outcomes, i.e. (P < 0.00).


Conclusion: The current investigation adequately established that the extracts of C. papaya has an anxiety-reducing impact on mice, suggesting that it may represent a novel strategy for the treatment of anxiety.

Abstract 470 | pdf Downloads 132

References

Ahsan SK, Shah AH, Tanira MOM, Ahmad MS, Tariq M, Ageel AM. 1990. Studies on some herbal drugs used against kidney stones in Saudi folk medicine. Fitoterapia. 61(5):435-438.
2. Armario A, Gavaldà A, Martí O. 1988. Forced swimming test in rats: effect of desipramine administration and the period of exposure to the test on struggling behavior, swimming, immobility and defecation rate. Eur. J. Pharmacol. 158(3):207-212.
3. Ayoola P, Adeyeye A. 2010. Phytochemical and nutrient evaluation of Carica papaya (pawpaw) leaves. Ijrras. 5(3):325-328.
4. Ayotunde EO, Ofem BO. 2008. Acute and chronic toxicity of pawpaw (Carica papaya) seed powder to adult Nile tilapia (Oreochromis niloticus Linne 1757). Afr. J. Biotechnol. 7(13).
5. Borsini F, Meli A. 1988. Is the forced swimming test a suitable model for revealing antidepressant activity? Psychopharmacology. 94(2):147-160.
6. Bourin M, Hascoët M. 2003. The mouse light/dark box test. Eur. J. Pharmacol. 463(1-3):55-65.
7. Bronikowski AM, Carter PA, Swallow JG, Girard IA, Rhodes JS, Garland T. 2001. Open-field behavior of house mice selectively bred for high voluntary wheel-running. Behav. Genet. 31(3):309-316.
8. Carobrez A, Bertoglio L. 2005. Ethological and temporal analyses of anxiety-like behavior: the elevated plus-maze model 20 years on. Neurosci. Biobehav. Rev. 29(8):1193-1205.
9. Carola V, D'Olimpio F, Brunamonti E, Mangia F, Renzi P. 2002. Evaluation of the elevated plus-maze and open-field tests for the assessment of anxiety-related behaviour in inbred mice. Behav. Brain Res. 134(1-2):49-57.
10. Carroll D, Ring C, Suter M, Willemsen G. 2000. The effects of an oral multivitamin combination with calcium, magnesium, and zinc on psychological well-being in healthy young male volunteers: a double-blind placebo-controlled trial. Psychopharmacology. 150(2):220-225.
11. Crawley J, Goodwin FK. 1980. Preliminary report of a simple animal behavior model for the anxiolytic effects of benzodiazepines. Pharmacol. Biochem. Behav. 13(2):167-170.
12. Cryan JF, Sweeney FF. 2011. The age of anxiety: role of animal models of anxiolytic action in drug discovery. Br. J. Pharmacol. 164(4):1129-1161.
13. Cryan JF, Valentino RJ, Lucki I. 2005. Assessing substrates underlying the behavioral effects of antidepressants using the modified rat forced swimming test. Neurosci. Biobehav. Rev. 29(4-5):547-569.
14. Detke MJ, Rickels M, Lucki I. 1995. Active behaviors in the rat forced swimming test differentially produced by serotonergic and noradrenergic antidepressants. Psychopharmacology. 121(1):66-72.
15. mDiMeglio L, Imel E. 2019. Calcium and Phosphate: Hormonal Regulation and Metabolism In: Burr DB, Allen MR (eds) Basic and Applied Bone Biology. Elsevier, Academic Press, New York.
16. Doukkali Z, Taghzouti K, Bouidida E, Nadjmouddine M, Cherrah Y, Alaoui K. 2015. Evaluation of anxiolytic activity of methanolic extract of Urtica urens in a mice model. Behav. Brain Funct. 11(1):1-5.
17. Elliott BM, Grunberg NE. 2005. Effects of social and physical enrichment on open field activity differ in male and female Sprague–Dawley rats. Behav. Brain Res. 165(2):187-196.
18. File SE, Wardill AG. 1975. Validity of head-dipping as a measure of exploration in a modified hole-board. Psychopharmacologia. 44(1):53-59.
19. Gilani A, Jabeen Q, Ghayur M, Janbaz K, Akhtar M. 2005. Studies on the antihypertensive, antispasmodic, bronchodilator and hepatoprotective activities of the Carum copticum seed extract. J. Ethnopharmacol. 98(1-2):127-135.
20. Hart PC, Bergner CL, Smolinsky AN, Dufour BD, Egan RJ, LaPorte JL, Kalueff AV. 2010. Experimental models of anxiety for drug discovery and brain research. Mouse Models for Drug Discovery.299-321.
21. Hussein G, Miyashiro H, Nakamura N, Hattori M, Kakiuchi N, Shimotohno K. 2000. Inhibitory effects of Sudanese medicinal plant extracts on hepatitis C virus (HCV) protease. Phytother. Res. 14(7):510-516.
22. Ikeyi A, Ogbonna A, Eze F. 2013. Phytochemical analysis of paw-paw (Carica papaya) leaves. Int. J. Life Sci. Biotechnol. Pharma. Res. 2(3):347-351.
23. Jaiswal P, Kumar P, Singh V, Singh D. 2010. Carica papaya Linn: A potential source for various health problems. J. Pharm. Res. 3(5):998-1003.
24. Kliethermes CL, Crabbe JC. 2006. Pharmacological and genetic influences on hole-board behaviors in mice. Pharmacol. Biochem. Behav. 85(1):57-65.
25. Komatsu T, Chiba T, Yamaza H, Yamashita K, Shimada A, Hoshiyama Y, Henmi T, Ohtani H, Higami Y, de Cabo R. 2008. Manipulation of caloric content but not diet composition, attenuates the deficit in learning and memory of senescence-accelerated mouse strain P8. Exp. Gerontol. 43(4):339-346.
26. Lim TK. 2012. Edible medicinal and non-medicinal plants. Vol. 1. Springer.
27. Linder J, Brismar K, Beck‐Friis J, Saaf J, Wetterberg L. 1989. Calcium and magnesium concentrations in affective disorder: difference between plasma and serum in relation to symptoms. Acta Psychiatr. Scand. 80(6):527-537.
28. Mandillo S, Tucci V, Holter SM, Meziane H, Banchaabouchi MA, Kallnik M, Lad HV, Nolan PM, Ouagazzal A-M, Coghill EL. 2008. Reliability, robustness, and reproducibility in mouse behavioral phenotyping: a cross-laboratory study. Physiol. Genomics. 34(3):243-255.
29. Mill J, Galsworthy M, Paya‐Cano J, Sluyter F, Schalkwyk L, Plomin R, Asherson P. 2002. Home‐cage activity in heterogeneous stock (HS) mice as a model of baseline activity. Genes Brain Behav. . 1(3):166-173.
30. Ming R, Hou S, Feng Y, Yu Q, Dionne-Laporte A, Saw JH, Senin P, Wang W, Ly BV, Lewis KL. 2008. The draft genome of the transgenic tropical fruit tree papaya (Carica papaya Linnaeus). Nature. 452(7190):991-996.
31. Najam R. 2003. Pharmacological screening of some bioactive products from marine resources.
32. Najam R, Riaz B. 2016. Neuropharmacological screening of zamzam water revealed its anxiolytic and antidepressant effect. Int. J. Ther. Appl. 32:41-47.
33. Ngozi AI, George OG, Veronica IO, Sunday A, Tomi D-E, Bola O, Patience ND, Mojisola O, Alero O, Felix CEJSr et al. 2010. Phytochemical and antioxidant nutrient constituents of Carica papaya and Parquetina nigrescens extracts. 5(16):2201-2205.
34. Nogueira Neto JD, de Almeida AAC, da Silva Oliveira J, Dos Santos PS, de Sousa DP, de Freitas RM. 2013. Antioxidant effects of nerolidol in mice hippocampus after open field test. Neurochem. Res. 38(9):1861-1870.
35. Nwofia GE, Ojimelukwe P, Eji C. 2012. Chemical composition of leaves, fruit pulp and seeds in some Carica papaya (L) morphotypes. Int. J. Med. Aromat. Plants. 2(1):200-206.
36. Oloyede O. 2005. Chemical profile of unripe pulp of Carica papaya. Pak. J. Nutr. 4(6):379-381.
37. Parle M, Gurditta A. 2011. Basketful benefits of papaya. Int. Res. J. Pharm. 2(7):6-12.
38. Passera C, Spettoli P. 1981. Chemical composition of papaya seeds. Plant Foods Hum. Nutr. 31(1):77-83.
39. Samad N, Muneer A, Zaman A, Ayaz MM, Ahmad I. 2017. Banana fruit pulp and peel involved in antianxiety and antidepressant effects while invigorate memory performance in male mice: Possible role of potential antioxidants. Pak. J. Pharm. Sci. 30.
40. Selvaraj Y, Pal D, Subramanyam M, Iyer C. 1982. Changes in the chemical composition of four cultivars of papaya (Carica papaya L.) during growth and development. Int. J. Hortic. Sci. 57(1):135-143.
41. Steimer T. 2022. Animal models of anxiety disorders in rats and mice: some conceptual issues. Dialogues Clin. Neurosci.
42. Thanaraj T, Terry L. 2011. 17 Tropical Fruit [Banana, Pineapple, Papaya and Mango]. Health-promoting properties of fruit and vegetables, 352.
43. Van Loo P, Van der Meer E, Kruitwagen C, Koolhaas J, Van Zutphen L, Baumans V. 2004. Long-term effects of husbandry procedures on stress-related parameters in male mice of two strains. Laboratory Animals. 38(2):169-177.
44. Walia V, Garg C, Garg M. 2018. Anxiolytic-like effect of pyridoxine in mice by elevated plus maze and light and dark box: Evidence for the involvement of GABAergic and NO-sGC-cGMP pathway. Pharmacol. Biochem. Behav. 173:96-106.
45. Wronski T, Lowry P, Walsh C, Ignaszewski L. 1985. Skeletal alterations in ovariectomized rats. Calcif. Tissue Int. 37(3):324-328.
46. Yogiraj V, Goyal PK, Chauhan CS, Goyal A, Vyas B. 2014. Carica papaya Linn: an overview. Int. J. Herb. Med. 2(5):01-08.