Author(s):
Ermalyanti Fiskia, Dian Saphira M. Fahmi, Muhammad Fakhrur Rajih H.Y., Muhammad Zulfian A. Disi, Amran Nur
Email(s):
ermalyanti@unkhair.ac.id
DOI:
10.52711/0974-360X.2025.00323
Address:
Ermalyanti Fiskia*, Dian Saphira M. Fahmi, Muhammad Fakhrur Rajih H.Y., Muhammad Zulfian A. Disi, Amran Nur
Department of Pharmacy, Medical Faculty, Khairun University, North Maluku, Indonesia.
*Corresponding Author
Published In:
Volume - 18,
Issue - 5,
Year - 2025
ABSTRACT:
Nutmeg pulp (Myristica fragrans) is often found in Maluku and North Maluku, Indonesia. Nutmeg pulp contains many chemical compounds that have the potential to be used as medicinal ingredients, but it also contains toxic compounds, myristicin. This study aims to see the subchronic toxicity of ethanol extract of nutmeg pulp in white rats by administering the extract for 50 days. The test animals used were 20 female Wistar rats divided into four groups: the control group, NPE 125mg/kgbw, NPE 250mg/kgbw, and NPE 500mg/kgbw. The parameters observed were LD50 value, changes in behavior, body weight, organ index, macroscopic, and liver histopathology. The data obtained was then analyzed using One-way ANOVA. The results showed that there were no deaths of test animals and changes in behavior during administration of the extract with an LD50 value of 246,036 mg/kg, organ weights and body weights did not show significant differences compared to the control group (p>0.05), macroscopic observations showed that the liver of all brownish-red color group with a smooth and shiny surface, without any indications of toxicity and microscopically, liver cell histopathology showed mild damage in the form of necrosis at each dose, but was still within normal limits. Conclusion: In conclusion, Nutmeg pulp at doses of 125mg/kgbw, 250mg/kgbw, and 500mg/kgbw is safe for consumption as food or medicine
Cite this article:
Ermalyanti Fiskia, Dian Saphira M. Fahmi, Muhammad Fakhrur Rajih H.Y., Muhammad Zulfian A. Disi, Amran Nur. Subchronic Toxicity Studies of Nutmeg Pulp Ethanol Extract (Myristica fragrans H.) on Wistar Rats (Rattus norvegicus). Research Journal of Pharmacy and Technology. 2025;18(5):2256-0. doi: 10.52711/0974-360X.2025.00323
Cite(Electronic):
Ermalyanti Fiskia, Dian Saphira M. Fahmi, Muhammad Fakhrur Rajih H.Y., Muhammad Zulfian A. Disi, Amran Nur. Subchronic Toxicity Studies of Nutmeg Pulp Ethanol Extract (Myristica fragrans H.) on Wistar Rats (Rattus norvegicus). Research Journal of Pharmacy and Technology. 2025;18(5):2256-0. doi: 10.52711/0974-360X.2025.00323 Available on: https://rjptonline.org/AbstractView.aspx?PID=2025-18-5-46
REFERENCES:
1. Kuete, V. Myristica fragrans: A Review. In Medicinal Spices and Vegetables From Africa: Therapeutic Potential Against Metabolic, Inflammatory, Infectious And Systemic Diseases. 2017; 497–512. doi:10.1016/B978-0-12-809286-6.00023-6
2. Yuliet, Y., Sukandar, E. Y. Adnyana, K. In Vitro and in Vivo Antidiabetic Activity of Ethanol Extract and Fractions of Hibiscus Surattensis L Leaves. Indonesian Journal of Pharmaceutical Science And Technology Journal Homepage. 2018; 1(1):25-30. Doi: https://doi.org/10.24198/ijpst.v1i1.16120
3. Aryal, B. Et Al. Antidiabetic, Antimicrobial, and Molecular Profiling of Selected Medicinal Plants. Evidence-Based Complementary And Alternative Medicine. 2021; 1:1-15. doi: https://doi.org/10.1155/2021/5510099
4. Nur, A., Fiskia, E., Rahman, I. Anti-Inflammatory Activity of Nutmeg Pulp (Myristica fragrans Houtt.) in White Rats Induced by Carrageenan.. Jurnal Farmasi Indonesia. 2022; 4(1):10-16. doi: https://doi.org/10.35617/jfionline.v14i1.87
5. Williams, G. Disaster Medicine: A History. Am J Disaster Med. 2008; 3(3):125–130.
6. Kumar Verma, N. Myristica fragrans (Nutmeg): A Brief Review. 2021; 3(5): 133-137. doi: 10.36349/easjpp.2021.v03i05.004
7. Nagja, T., Vimal, K. and Sanjeev, A. Myristica fragrans: A Comprehensive Review. Int J Pharm Pharm Sci. 2016; 8(2): 27–30. doi: https://journals.innovareacademics.in/index.php/ijpps/article/view/8552
8. Jose H., Arya KR., Sindhu TJ., Syamjith P., Vinod KR., Sandhya S., A Descriptive Review on Myristica fragrans Houtt. Hygeia journal for drugs and medicines. 2016 May; 8(1): 35-43. doi: :10.15254/H.J.D.Med.8.2016.155
9. Dechayont, B. Et Al. Antimicrobial, Anti-Inflammatory and Antioxidant Activities of The Wood of Myristica fragrans. J Herbs Spices Med Plants. 2020;26(4):1-12. doi: 10.5958/0974-360X.2020.00307.8
10. Madhvi, S. K., Sharma, M., Iqbal, J., Younis, M. and Sheikh, R. Phytochemical Analysis, Total Flavonoid, Phenolic Contents and Antioxidant Activity of Extracts From The Leaves of Rhododendron arboreum. Res J Pharm Technol. 2020;13(4):1701-1706. Doi: 10.5958/0974-360X.2020.00307.8
11. Melakhessou, M. A., Benkiki, N. and Marref, S. E. Determination of Antioxidant Capacity, Flavonoids and Total Phenolic Content of Extracts From Atractylis flava Desf. Res J Pharm Technol. 2018;11(12);5221-5226. doi: 10.5958/0974-360X.2018.00952.6
12. Seneme, E. F., Santos, D. C. Dos, Silva, E. M. R., Franco, Y. E. M. and Longato, G. B. Pharmacological and Therapeutic Potential of Myristicin: A Literature Review. Molecules. 2021; 26(19):5914. doi: https://doi.org/10.3390/molecules26195914
13. Masyita, A. Et Al. Terpenes and Terpenoids As Main Bioactive Compounds of Essential Oils, Their Roles in Human Health and Potential Application As Natural Food Preservatives. Food Chem X. 2022; 13:1-14. doi: https://doi.org/10.1016/j.fochx.2022.100217
14. Weerakoon, T., Perera, W. P. R. T., Rajapaksha, H. and Liyanage, J. A. A Review On Bioactive Compounds And Pharmacological Activities of Myristica fragrans As A Medicinal Plant. 2021; 3(6); 1316-1320. doi:Https://Www.Researchgate.Net/Publication/353690024.
15. Nur, A. and Rahman, I. Test of the Analgesic Effect of Ethanol Extract of Nutmeg on White Rats. Kieraha Medical Journal. 2020; 2(2): 119-124. doi: https://doi.org/10.33387/kmj.v2i2.2751
16. Liunokas, A. B. and Karwur, F. F. Isolation and Identification of Chemical Components of Essential Oils of Fruit Flesh and Mace Based on the Age of Nutmeg Fruit (Myristica fragrans Houtt). Journal of Tropical Biology. 2020; 20(1): 69–77. doi: 10.29303/jbt.v20i1.1651
17. National Toxicology Program. NTP Technical Report on the Toxicity Studies of Myristicin (CASRN 607-91-0) Administered by Gavage to F344/NTac Rats and B6C3F1/N Mice: Toxicity Report 95 [Internet]. Research Triangle Park (NC): National Toxicology Program. 2019 Mar. doi: 10.22427/NTP-TOX-95
18. Saiful Bachri, M. Sub Chronic Effect of Ethanol Extract of Nutmeg (Myristica fragrans Houtt) Seed In Rat Kidney. In Proceeding of International Safety Management Of Central Cytotoxic Reconstitution. 2013: 165–169.
19. Cao, Z. Et Al. Hepatotoxicity of Nutmeg: A Pilot Study Based on Metabolomics. Biomedicine and Pharmacotherapy. 2020; 131: 1-10. doi: https://doi.org/10.1016/j.biopha.2020.110780
20. Xia, W., Cao, Z., Zhang, X. and Gao, L. A Proteomics Study on The Mechanism of Nutmeg-Induced Hepatotoxicity. Molecules. 2021; 26(6):1748. doi: https://doi.org/10.3390/molecules26061748
21. Sun, J., Fuyin Z., Zhenlei W., Weina Z., Xiudong Y., Hongli Z., Peng W. Effect of Simmering Technology on Components and Activity of Myristica fragrans Houtt. Molecules. 2023; 28(22):7627. doi: 10.3390/molecules28227627.
22. Morris-Schaffer, K. and Mccoy, M. J. A Review of The LD50 and Its Current Role In Hazard Communication. Acs Chemical Health And Safety. 2021; 28(1): 25–33. doi: 10.1021/acs.chas.0c00096
23. Evaluation of Antidiabetic, Phytochemical and Acute Toxicity of The Methanol Seed Extract of Senna occidentalis Linn. Tropical Journal of Natural Product Research.2021; 5(6): 1101–1105. Doi: doi.org/10.26538/tjnpr/v5i6.20
24. Kpemissi, M. et al. Acute and Subchronic Oral Toxicity Assessments of Combretum micranthum (Combretaceae) In Wistar Rats. Toxicol Rep. 2020; Jan; 18(7): 162–168. doi: 10.1016/j.toxrep.2020.01.007
25. Al-Rekabi, F. M. K., Asker, S. J., Shwaish, M. M. Acute and Subchronic Interaction Between Metformin and Meloxicam In Mice. Research Journal of Pharmacy and Technology. 2018 June; 11(6): 2336. doi: 10.5958/0974-360X.2018.00434.1
26. Al-Rekabi, F. M. K., Askar, S. J., Yousif, E. H. The Toxic Effects of Subchronic Exposure to Methanolic Extract of Stigma of Crocous Sativa L (Saffron) in Mice. Research Journal of Pharmacy and Technology. 2019;12(5): 2473. doi: 10.5958/0974-360X.2019.00415.3
27. National Agency of Drug and Food Control. Guidelines for In Vivo Preclinical Toxicity Testing. In Food and Drug Supervisory Agency Regulation Number 10 of 2022; 1-7.
28. Apriandi, A., Tarman, K., Sugita, P. Acute Toxicity Water Extract f Meretrix linnaeus In Vivo on Sprague Dawley Rats. Asian Journal of Aquatic Sciences. 2021; 4(3): 171-177. doi: 10.31258/ajoas.4.3.171-177
29. Widjiati, Dewita, Hendrawan, V. F., Purwantari, K. E., Wajdi, S. A., Zulfarniasyah, A. B., Putri, A. S., Rahmawati, M. A., and Al-Ilmi, M. F. Histopathologic Changes in Liver Tissue From Cadmium Intoxicated Mice And Treated With Curcumin During Pregnancy. Research Journal of Pharmacy and Technology. 2018; 11(3): 863-866. doi: https://doi.org/10.5958/0974-360X.2018.00160.9
30. Ban J. M., Faeza A. Z., A. The Effect of Pseudoephedrine (Sudafed) on Kinetic Activity and Histology of Livers and Kidneys in Albino Mice. Research Journal of Pharmacy and Technology. 2021; 14(9): 5015–5018. doi:10.52711/0974-360x.2021.00874.
31. Vdoviaková K, Petrovová E, Maloveská M, Krešáková L, Teleky J, Elias MZ, Petrášová D. Surgical Anatomy of The Gastrointestinal Tract and Its Vasculature In The Laboratory Rat. Gastroenterology Research and Practice. 2016; 1-11. doi: 10.1155/2016/2632368
32. Alipin, K., Rina Nur Azizah, N. Morfologis Dan Beratrelatif Organ Hati Tikus Yang Diinduksi Karagenan Setelah Pemberian Ekstrak Kombinasi Rimpang Temulawak Dan Buah Belimbing Wuluh. In Seminar Nasional Pendidikan Biologi Dan Saintek. 2021; 243–247.
33. K. О. Kalko, O. Ya. Mishchenko, L. V. Derymedvid, M. Yu. Zolotaikina, Т. M. Gontova, V. V. Mashtaler, S. A. Kutsenko. A Screening Study Of Hepatoprotective Activity Of Liquid Extract From Common Tansy tanacetum Vulgare L. Herb In The Setting of Subchronic Hepatitis In Rats. Research Journal of Pharmacy and Technology. 2018; 11(10): 4393. 10.5958/0974-360X.2018.00803.X