Research Article
BibTex RIS Cite

Evaluation of developmental toxicity of Unani herbal formulation Habbe Sara in zebrafish (Danio rerio)

Year 2024, Volume: 28 Issue: 5, 1526 - 1535, 28.06.2025

Abusufyan Shaikh Mehreen Falke Saba Shaikh Aditi Chorage Kajal Kesharvani Adnan Wadkar Akhil Nair Ismaeel Sayyed Shariq Syed

Abstract

Habbe Sara is an herbal formulation used in the Unani system of medicine to treat convulsions in adults and children. It is believed to strengthen the brain and nervous system, reducing the frequency of fits. In this study, the effects of various concentrations of Habbe Sara ranging from 50 to 400 ppm on in zebrafish were examined. The study found that increasing concentrations of Habbe Sara resulted in higher mortality rates with an LC50 value of 251.18 ppm. In addition, its higher concentrations showed delayed growth, decreased in heartbeat rate, reduced hatchability, and various developmental defects in the treated embryos. Therefore, caution should be exercised when administering high doses of Habbe Sara to pregnant women.

Keywords

Teratogenic effect Habbe Sara developmental defect zebrafish toxicity

References

  • [1] Tomson T, Battino D. Teratogenic effects of antiepileptic drugs. Seizure Eur J Epilep. 2008; 17(2): 166–171. https://doi.org/10.1016/j.seizure.2007.11.016
  • [2] Tomson T, Battino D, Perucca E. Teratogenicity of antiepileptic drugs. Curr Opin Neurol. 2019; 32(2): 246–252. https://doi.org/10.1097/WCO.0000000000000659
  • [3] Güveli B, Rosti R, Güzeltaş A, Tuna E, Ataklı D, Sencer S, Yekeler E, Kayserili H, Dirican A, Bebek N, Baykan B, Gökyiğit A, Gürses C. Teratogenicity of antiepileptic drugs. Clin Psychopharmacol Neurosci. 2017; 15(1): 19–27. https://doi.org/10.9758/cpn.2017.15.1.19
  • [4] Asjad H, Akhtar M, Asad M, Din B, Gulzar F, Hassnain F. In vitro antioxidant activity of Habbe sara [Unani Medicine] prescribed for febrile convulsions. J Pharm Altern Med. 2012; 2: 29–35. https://iiste.org/Journals/index.php/JPAM/article/view/3519
  • [5] Li J, Copmans D, Partoens M, Hunyadi B, Luyten W, de Witte P. Zebrafish based screening of antiseizure plants used in traditional Chinese medicine: Magnolia officinalis extract and its constituents Magnolol and Honokiol exhibit potent anticonvulsant activity in a therapy-resistant epilepsy model. ACS Chem Neurosci. 2020; 11(5): 730–742. https://doi.org/10.1021/acschemneuro.9b00610
  • [6] McGrath P, Li Q. Zebrafish: a predictive model for assessing drug-induced toxicity. Drug Discov Today. 2008; 13(9–10): 394–401. https://doi.org/10.1016/j.drudis.2008.03.002
  • [7] Sipes N, Padilla S, Knudsen T. Zebrafish-As an integrative model for twenty-first century toxicity testing. Birth Defects Res C Embryo Today. 2011; 93(3): 256–267. https://doi.org/10.1002/bdrc.20214
  • [8] Kannan R, Iniyan A, Vincent S. Chemical genetic effects of Sargassum wightii during embryonic development in zebrafish. Indian J Pharmacol. 2015; 47(2): 195–198. https://doi.org/10.4103/0253-7613.153429
  • [9] Westerfield M. The Zebrafish Book. A guide for the laboratory use of Zebrafish (Danio rerio), Fifth ed., University of Oregon Press, Eugene 2007.
  • [10] Wixon J. Danio rerio, the zebrafish. Yeast. 2000; 17(3): 225–231. https://doi.org/10.1002/1097-0061(20000930)17:3<225::aid-yea34>3.0.co;2-5
  • [11] Zon L, Peterson R. In vivo drug discovery in the zebrafish. Nat Rev Drug Discov. 2005; 4: 35–44. https://doi.org/10.1038/nrd1606
  • [12] Lieschke G, Currie P. Animal models of human disease: Zebrafish swim into view. Nat Rev Genet. 2007; 8: 353–367. https://doi.org/10.1038/nrg2091
  • [13] Miyawaki I. Application of zebrafish to safety evaluation in drug discovery. J Toxicol Pathol. 2020; 33(4): 197–210. https://doi.org/10.1293/tox.2020-0021
  • [14] Basha P, Rani A. Cadmium-induced antioxidant defense mechanism in freshwater teleost Oreochromis mossambicus (Tilapia). Ecotoxicol Environ Saf. 2003; 56(2): 218–221. https://doi.org/10.1016/S0147-6513(03)00028-9
  • [15] Shaikh A, Kohale K, Ibrahim M, Khan M. Teratogenic effects of aqueous extract of Ficus glomerata leaf during embryonic development in zebrafish (Danio rerio). J Appl Pharm Sci. 2019; 9(5): 107–111. https://doi.org/10.7324/JAPS.2019.90514
  • [16] Melançon E, Liu D, Westerfield M, Eisen J. Path finding by identified zebrafish motoneurons in the absence of muscle pioneers. J Neurosci. 1997; 17(20): 7796–7804. https://doi.org/10.1523/JNEUROSCI.17-20-07796.1997
  • [17] Menelaou E, Husbands E, Pollet R, Coutts C, Ali D, Svoboda K. Embryonic motor activity and implications for regulating motoneuron axonal pathfinding in zebrafish. Eur J Neurosci. 2008; 28(6): 1080–1096. https://doi.org/10.1111/j.1460-9568.2008.06418.x
  • [18] Barreto A, Santos J, Capitao A, Eusebio R, Pinheiro E, Machado A, Rocha L, Calisto V, Amorim M, Maria V. Assessment of diphenhydramine toxicity – Is its mode of action conserved between human and zebrafish? Environ Int. 2022; 164: 107263. https://doi.org/10.1016/j.envint.2022.107263
  • [19] Luca E, Zaccaria G, Hadhoud M, Rizzo G, Ponzini R, Morbiducci U, Santoro M. ZebraBeat: A flexible platform for the analysis of the cardiac rate in zebrafish embryos. Sci Rep. 2014; 4: 4898. https://doi.org/10.1038/srep04898
  • [20] Wang R, Liu K, Zhang Y, Chen X, Wang X. Evaluation of the developmental toxicity induced by E804 in zebrafish embryos. Front Pharmacol. 2020; 11:32. https://doi.org/10.3389/fphar.2020.00032
  • [21] Lee J, Park H, Lim W, Song G. Benfuresate induces developmental toxicity in zebrafish larvae by generating apoptosis and pathological modifications. Pestic Biochem Physiol. 2021; 172: 104751. https://doi.org/10.1016/j.pestbp.2020.104751
  • [22] Zoupa M, Machera K. Zebrafish as an alternative vertebrate model for investigating developmental toxicity: the triadimefon example. Int J Mol Sci. 2017; 18(4): 817. https://doi.org/10.3390/ijms18040817
  • [23] Song C, Song S, Liang H, Liu X. Effect of Camptothecin on the embryonic development and angiogenesis of zebrafish embryos. Adv Mat Res. 2013; 750–752: 1472–1475. https://doi.org/10.4028/www.scientific.net/AMR.750-752.1472
  • [24] Peng W, Lee Y, Chau Y, Lu K, Kung H. Short-term exposure of zebrafish embryos to arecoline leads to retarded growth, motor impairment, and somite muscle fiber changes. Zebrafish. 2015; 12: 58–70. https://doi.org/10.1089/zeb.2014.1010
  • [25] Sant K, Laragy A. Zebrafish as a model for toxicological perturbation of yolk and nutrition in the early embryo. Curr Environ Health Rep. 2018; 5: 125–133. https://doi.org/10.1007/s40572-018-0183-2
  • [26] Teixidó E, Piqué E, Catalán J, Llobet J. Assessment of developmental delay in the zebrafish embryo teratogenicity assay. Toxicol in Vitro. 2013; 27: 469–478. https://doi.org/10.1016/j.tiv.2012.07.010
  • [27] Xie H, Li M, Kang Y, Zhang J, Zhao C. Zebrafish: an important model for understanding scoliosis. Cell Mol Life Sci. 2022; 79: 506. https://doi.org/10.1007/s00018-022-04534-5
  • [28] Ponrasu T, Ganeshkumar M, Suguna L. Developmental toxicity evaluation of ethanolic extract of Annona squamosa in zebrafish (Danio rerio) embryo. J Pharm Res. 2012; 5(1): 277–279.
  • [29] Majewski M, Kasica N, Jakubowski P, Podlasz P. Influence of fresh garlic (Allium sativum L.) juice on zebrafish (Danio Rerio) embryos developmental effects. J Elem. 2017; 22(2): 475–486. https://doi.org/10.5601/jelem.2016.21.4.1261
  • [30] Dulay R, Kalaw S, Reyes R, Alfonso N, Eguchi F. Teratogenic and toxic effects of Lingzhi or Reishi medicinal mushroom, Ganoderma lucidum (W.Curt.:Fr.) P. Karst. (Higher basidiomycetes), on zebrafish embryo as model. Int J Med Mushrooms. 2012; 14(5): 507–512. https://doi.org/10.1615/IntJMedMushr.v14.i5.90
  • [31] Khandelwal K. Practical pharmacognosy techniques and experiments. 22nd ed., Vrunda KS, editor. India: Nirali Prakashan; 2013, pp. 25.1-25.6.
  • [32] OECD. Test No. 236: Fish embryo acute toxicity (FET) Test, OECD guidelines for the testing of chemicals, Section 2. OECD Publishing, Paris, 2013.
  • [33] Wibowo I, Permadi K, Hartati R, Damayanti S. Ethanolic extract of pomegranate (Punica granatum L) peel: Acute toxicity tests on zebrafish (Danio rerio) embryos and its toxicity prediction by in silico. J Appl Pharm Sci. 2018; 8(6): 82–86. https://doi.org/10.7324/JAPS.2018.8611
  • [34] Nagel R. DarT: The embryo test with the zebrafish Danio rerio-a general model in ecotoxicology and toxicology. Altex. 2002; 19(1): 38–48.
  • [35] Hoage T, Ding Y, Xu X. Quantifying cardiac functions in embryonic and adult zebrafish. In: Peng X, Antonyak M. (Eds). Cardiovascular Development: Methods in Molecular Biology. Humana Press, 2012, pp. 11–20.
  • [36] Abidin A, Visepomaran S, Balan S, Bahari H. Evaluation of effect of ethanol extraction of Graptophyllum pictum on zebrafish (Danio rerio) embryo model through toxicity assay assessment. J Toxicol Risk Assess. 2021; 7:040. https://doi.org/10.23937/2572-4061.1510040
There are 36 citations in total.

Details

Primary Language English
Subjects Toxicology
Journal Section Articles
Authors

Abusufyan Shaikh 0000-0003-4225-1548

Mehreen Falke 0009-0007-3968-5704

Saba Shaikh 0000-0003-0432-1285

Aditi Chorage 0009-0001-0711-0160

Kajal Kesharvani 0009-0004-4477-1875

Adnan Wadkar 0009-0009-8391-2745

Akhil Nair 0009-0003-3530-2308

Ismaeel Sayyed 0009-0009-8758-7417

Shariq Syed 0009-0008-3798-5153

Publication Date June 28, 2025
Submission Date October 19, 2023
Acceptance Date January 9, 2024
Published in Issue Year 2024 Volume: 28 Issue: 5

Cite

APA Shaikh, A., Falke, M., Shaikh, S., Chorage, A., et al. (2025). Evaluation of developmental toxicity of Unani herbal formulation Habbe Sara in zebrafish (Danio rerio). Journal of Research in Pharmacy, 28(5), 1526-1535.
AMA Shaikh A, Falke M, Shaikh S, Chorage A, Kesharvani K, Wadkar A, Nair A, Sayyed I, Syed S. Evaluation of developmental toxicity of Unani herbal formulation Habbe Sara in zebrafish (Danio rerio). J. Res. Pharm. July 2025;28(5):1526-1535.
Chicago Shaikh, Abusufyan, Mehreen Falke, Saba Shaikh, Aditi Chorage, Kajal Kesharvani, Adnan Wadkar, Akhil Nair, Ismaeel Sayyed, and Shariq Syed. “Evaluation of Developmental Toxicity of Unani Herbal Formulation Habbe Sara in Zebrafish (Danio Rerio)”. Journal of Research in Pharmacy 28, no. 5 (July 2025): 1526-35.
EndNote Shaikh A, Falke M, Shaikh S, Chorage A, Kesharvani K, Wadkar A, Nair A, Sayyed I, Syed S (July 1, 2025) Evaluation of developmental toxicity of Unani herbal formulation Habbe Sara in zebrafish (Danio rerio). Journal of Research in Pharmacy 28 5 1526–1535.
IEEE A. Shaikh, M. Falke, S. Shaikh, A. Chorage, K. Kesharvani, A. Wadkar, A. Nair, I. Sayyed, and S. Syed, “Evaluation of developmental toxicity of Unani herbal formulation Habbe Sara in zebrafish (Danio rerio)”, J. Res. Pharm., vol. 28, no. 5, pp. 1526–1535, 2025.
ISNAD Shaikh, Abusufyan et al. “Evaluation of Developmental Toxicity of Unani Herbal Formulation Habbe Sara in Zebrafish (Danio Rerio)”. Journal of Research in Pharmacy 28/5 (July 2025), 1526-1535.
JAMA Shaikh A, Falke M, Shaikh S, Chorage A, Kesharvani K, Wadkar A, Nair A, Sayyed I, Syed S. Evaluation of developmental toxicity of Unani herbal formulation Habbe Sara in zebrafish (Danio rerio). J. Res. Pharm. 2025;28:1526–1535.
MLA Shaikh, Abusufyan et al. “Evaluation of Developmental Toxicity of Unani Herbal Formulation Habbe Sara in Zebrafish (Danio Rerio)”. Journal of Research in Pharmacy, vol. 28, no. 5, 2025, pp. 1526-35.
Vancouver Shaikh A, Falke M, Shaikh S, Chorage A, Kesharvani K, Wadkar A, Nair A, Sayyed I, Syed S. Evaluation of developmental toxicity of Unani herbal formulation Habbe Sara in zebrafish (Danio rerio). J. Res. Pharm. 2025;28(5):1526-35.