Acute and Subchronic Toxicity Study of the Ethanol Extracts from Ficus deltoidea Leaves in Male Mice

Authors

  • Rudy Agung Nugroho Laboratorium Fisiologi, Perkembangan dan Molekuler Hewan, Jurusan Biologi Fakultas Matematika dan Ilmu Pengetahuan Alam Universitas Mulawarman, Samarinda, Kalimantan Timur
  • Retno Aryani Laboratorium Fisiologi, Perkembangan dan Molekuler Hewan, Jurusan Biologi Fakultas Matematika dan Ilmu Pengetahuan Alam Universitas Mulawarman, Samarinda, Kalimantan Timur
  • Hetty Manurung Laboratorium Fisiologi Tumbuhan, Jurusan Biologi Fakultas Matematika dan Ilmu Pengetahuan Alam Universitas Mulawarman, Samarinda, Kalimantan Timur
  • Rudianto Rudianto Laboratorium Fisiologi, Perkembangan, dan Molekuler Hewan, Jurusan Biologi, Fakultas Matematika dan Ilmu Pengetahuan Alam, Universitas Mulawarman, Samarinda, Kalimantan Timur, Indoensia
  • Widha Prahastika Laboratorium Anatomi dan mikroteknik Hewan, Jurusan Biologi Fakultas Matematika dan Ilmu Pengetahuan Alam Universitas Mulawarman, Samarinda, Kalimantan Timur
  • Amelia Juwita Laboratorium Fisiologi, Perkembangan dan Molekuler Hewan, Jurusan Biologi Fakultas Matematika dan Ilmu Pengetahuan Alam Universitas Mulawarman, Samarinda, Kalimantan Timur
  • Abdul Khafizh Alfarisi Laboratorium Fisiologi, Perkembangan dan Molekuler Hewan, Jurusan Biologi Fakultas Matematika dan Ilmu Pengetahuan Alam Universitas Mulawarman, Samarinda, Kalimantan Timur
  • Nur Ainun Oktavia Pusparini Laboratorium Fisiologi, Perkembangan dan Molekuler Hewan, Jurusan Biologi Fakultas Matematika dan Ilmu Pengetahuan Alam Universitas Mulawarman, Samarinda, Kalimantan Timur
  • Agnesia Lalong Laboratorium Fisiologi, Perkembangan dan Molekuler Hewan, Jurusan Biologi Fakultas Matematika dan Ilmu Pengetahuan Alam Universitas Mulawarman, Samarinda, Kalimantan Timur

DOI:

https://doi.org/10.3889/oamjms.2020.3989

Keywords:

Ficus deltoidea, Acute and subchronic toxicity, Mice, Hematology

Abstract

BACKGROUND: Ficus deltoidea Jack. leaves have a great potential as traditional medicine, but the safety level of its use is still unknown.

AIM: This study aimed to determine the phytochemical contents of the ethanol extract of F. deltoidea leaves and evaluate the level of safety and toxicity through acute and subchronic toxicity tests in mice (Mus musculus).

METHODS: The ethanol extract of F. deltoidea leaves was determined for phytochemical contents such as alkaloids, phenolics, flavonoids, coumarin, steroids, saponins, carotenoids, and tannins. In the acute toxicity test, 10 male mice were divided into a control group and the extract treatment group with 2000 mg/kg body weight (BW) dose for 14 days to identify signs of toxicity and mortality. Meanwhile, in the subchronic toxicity test, 25 male mice were divided into control and four treatment groups with various doses (125, 250, 500, and 1000 mg/kg BW), respectively, for 28 days. The toxicological effect was evaluated by observing behavior, signs of toxicity, and changes in BW. At the end of the treatment, hematological and biochemical evaluations were also measured.

RESULTS: The results showed that the ethanol extract of F. deltoidea Jack leaves qualitatively contains alkaloids, phenolic, flavonoids, coumarin, and steroids, whereas quantitatively total phenolics, flavonoids, and IC50 were 107.6583211 μg GA/mg, 175.9103641 μg CE/mg, and 103.7484 μg/mL. Moreover, 2000 mg/kg BW dose resulted in no symptoms of toxicity and mortality, indicating that the 50% lethal dose (LD50) was above 2000 mg/kg BW. Meanwhile, there were no behavioral changes, significant differences in weight changes, hematological parameters, and serum biochemistry of mice in subchronic toxicity tests.

CONCLUSION: The present study shows that acute and subchronic oral administration of the ethanol extract of F. deltoidea leaves for male mice does not induce clinical symptoms of toxicity or mortality. The LD50 of the ethanol extract of F. deltoidea leaves for mice >2000 mg/kg is considered as practically non-toxic.

Downloads

Download data is not yet available.

Metrics

Metrics Loading ...

Plum Analytics Artifact Widget Block

References

Ekor M. The growing use of herbal medicines: Issues relating to adverse reactions and challenges in monitoring safety. Front Pharmacol. 2014;4:177. https://doi.org/10.3389/fphar.2013.00177 PMid:24454289

Azis NA, Agarwal R, Ismail NM, Ismail NH, Kamal MSA, Radjeni Z, et al. Blood pressure lowering effect of Ficus deltoidea var kunstleri in spontaneously hypertensive rats: Possible involvement of renin-angiotensin-aldosterone system, endothelial function and anti-oxidant system. Mol Biol Rep. 2019;46(3):2841-9. https://doi.org/10.1007/ s11033-019-04730-w PMid:30977084

Afzan A, Kasim N, Ismail NH, Azmi N, Ali AM, Mat N, et al. Differentiation of Ficus deltoidea varieties and chemical marker determination by UHPLC-TOFMS metabolomics for establishing quality control criteria of this popular Malaysian medicinal herb. Metabolomics. 2019;15(3):35. https://doi.org/10.1007/ s11306-019-1489-2 PMid:30830457

Fauzi F, Widodo H. Aphrodisiac plants used by Dayak ethnic in Central Kalimantan Province, Indonesia. Biodivers J Biol Divers. 2019;20(7):1859-65. https://doi.org/10.13057/biodiv/d200710

Sundari S, Wardah W. Ethnobotany study of dayak society medicinal plants utilization in Uut Murung district, Murung Raya Regency, Central Kalimantan. In: The 2018 International Conference on Biosphere Reserve: The Role of Stakeholders in Mainstreaming Natural Resources Related to Agenda 2030, Sustainable Development Goals. Palembang, South Sumatera, Indonesia: IOP Publishing; 2019. p. 012005. https://doi. org/10.1088/1755-1315/298/1/012005

Salleh N, Ahmad VN. In vitro effect of Ficus deltoidea on the contraction of isolated rat’s uteri is mediated via multiple receptors binding and is dependent on extracellular calcium. BMC Complement Altern Med. 2013;13:359. https://doi. org/10.1186/1472-6882-13-359 PMid:24330515

Mustaffa NA, Hasham R, Sarmidi MR. An in vitro study of wound healing activity of Ficus deltoidea Leaf extract. J Teknol. 2015;77(3):1-6. https://doi.org/10.11113/jt.v77.6008

Asis J, Yusoff N, Nashriyah M. Allelopathic assesments of Ficus deltoidea jack varieties and Ficus microcarpa L.f. (Moraceae) on Lactuca sativa L. Seed. J Agrobiotechnol. 2018;9(1S):214-21.

Isa MN, Ajit A, Naila A, Sulaiman A. Effect of Microwave Assisted Hydrodistillation Extraction on Extracts of Ficus deltoidea Materials Today. Vol. 5. Proceedings; 2018. p. 21772-9. https:// doi.org/10.1016/j.matpr.2018.07.031

Bodeker G, Shekar S. Health and Beauty from the Rainforest: Malaysian Traditions of Ramuan. USA: Didier Millet, Csi; 2009.

Neergheen-Bhujun VS. Underestimating the toxicological challenges associated with the use of herbal medicinal products in developing countries. Biomed Res Int. 2013;2013:804086. https://doi.org/10.1155/2013/804086 PMid:24163821

Upton R, Graff A, Jolliffe G, Länger R, Williamson E. American Herbal Pharmacopoeia: Botanical Pharmacognosy-Microscopic Characterization of Botanical Medicines. USA: CRC Press; 2016. https://doi.org/10.1201/b10413

Yau WP, Goh CH, Koh HL. Quality Control and Quality Assurance of Phytomedicines: Key Considerations, Methods, and Analytical Challenges USA: John Wiley & Sons, Inc.; 2015. https://doi.org/10.1002/9781119006039.ch2

Schuppan D, Dayan AD, Charlesworth FA. The Contribution of Acute Toxicity Testing to the Evaluation of Pharmaceuticals. Netherland: Springer; 2014. https://doi. org/10.1007/978-3-642-70390-4_10

Traesel GK, de Souza JC, de Barros AL, Souza MA, Schmitz WO, Muzzi RM, et al. Acute and subacute (28 days) oral toxicity assessment of the oil extracted from Acrocomia aculeata pulp in rats. Food Chem Toxicol. 2014;74:320-25. https://doi.org/10.1016/j.fct.2014.10.026 PMid:25445758

Yang M, Wu Z, Wang Y, Kai G, Singor Njateng GS, Cai S, et al. Acute and subacute toxicity evaluation of ethanol extract from aerial parts of Epigynum auritum in mice. Food Chem Toxicol. 2019;131:110534. https://doi.org/10.1016/j.fct.2019.05.042 PMid:31150781

Molyneux P. The use of the stable free radical diphenylpicrylhydrazyl (DPPH) for estimating antioxidant activity. Songklanakarin J Sci Technol. 2004;26(2):211-9.

Brown AP, Dinger N, Levine BS. Stress produced by gavage administration in the rat. Contemp Top Lab Anim Sci. 2000;39(1):17-21. PMid:11178310

Dung NT, Kim JM, Kang SC. Chemical composition, antimicrobial and antioxidant activities of the essential oil and the ethanol extract of Cleistocalyx operculatus (Roxb.) Merr and Perry buds. Food Chem Toxicol. 2008;46(12):3632-9. https:// doi.org/10.1016/j.fct.2008.09.013 PMid:18838098

Zhang QH, Zhang L. research advance in chemical composition and pharmacological action of Chrysanthemum morifolium. Food and Drug. 2007;2:224-6.

Zhao L, Yang L, Liu Y, Li C, Kang W. Antimicrobial activity of seven species Chrysanthemum morifolium ramat cultivated in kaifeng. Mod Pharm Res. 2009;2:82-5.

Sun W, Shahrajabian MH, Cheng Q. Anise (Pimpinella anisum L.), a dominant spice and traditional medicinal herb for both food and medicinal purposes. Cogent Biol. 2019;5(1673688):1-25. https:// doi.org/10.1080/23312025.2019.1673688

Chen X, Gu N, Xue C, Li BR. Plant flavonoid taxifolin inhibits the growth, migration and invasion of human osteosarcoma cells. Mol Med Rep. 2018;17(2):3239-45. https://doi.org/10.3892/ mmr.2017.8271 PMid:29257319

Khalid M, Bilal M, Huang DF. Role of flavonoids in plant interactions with the environment and against human pathogens-a review. J Integr. 2019;18(1):211-30.

Perez-Vizcaino F, Fraga CG. Research trends in flavonoids and health. Arch Biochem Biophys. 2018;646:107-12. PMid:29580946

Vicente O, Boscaiu M. Flavonoids: Antioxidant compounds for plant defence and for a healthy human diet. Not Bot Horti Agrobo. 2018;46(1):14-21. https://doi.org/10.15835/nbha46110992

Mudimba TN, Maitho T, Mbaria J, Taderera T. Hematotoxicity assessment of phytochemicals from aqueous leaf extracts of Carpobrotus edulis. J Phytopharmacol. 2019;8(4):173-56. https://doi.org/10.31254/phyto.2019.8405

El-Sayed MA, Shaltot O, Yousef MI, El-Difrawy EA. protective effect of aerial parts of Portulaca oleracea and Ficus carica Leaves against diclofenac-sodium induced hepatotoxicity in rats. J Food Nutr Sci. 2019;7(1):1-7. https://doi.org/10.11648/j. jfns.20190701.11

Michalowicz J, Duda W. Phenols sources and toxicity. Pol J Environ. 2007;16(3):347-62.

Ames BN, Profet M, Gold LS. Dietary Carcinogens and Mutagens from Plants. USA: CRC Press; 2018.

Farsi E, Shafaei A, Hor SY, Ahamed MB, Yam MF, Asmawi MZ, et al. Genotoxicity and acute and subchronic toxicity studies of a standardized methanolic extract of Ficus deltoidea leaves. Clinics (Sao Paulo). 2013;68(6):865-75. https://doi.org/10.6061/ clinics/2013(06)23 PMid:23778480

Ukwuani A, Abubakar M, Hassan S, Agaie B. Toxicological studies of hydromethanolic leaves extract of Grewia crenata. Int J Pharm Sci Drug Res. 2012;4(4):4245-9.

Liju VB, Jeena K, Kuttan R. Acute and subchronic toxicity as well as mutagenic evaluation of essential oil from turmeric (Curcuma longa L). Food Chem Toxicol. 2013;53:52-61. https:// doi.org/10.1016/j.fct.2012.11.027 PMid:23201370

Sireeratawong S, Lertprasertsuke N, Srisawat U, Thuppia A, Ngamjariyawat A, Suwanlikhid N, et al. Acute and subchronic toxicity study of the water extract from root of Sida rhombifolia Linn. In rate. Songklanakarin J Sci Technol. 2008;30(6):729-37.

Duan W, Liang X. Technical Guidelines Assembly of Veterinary Medicine Research. Beijing: Chemical Industry Press; 2011.

Kifayatullah M. Toxicological investigation of ethanolic extract of Epipremnum aureum in rodents. J Appl Pharma Sci. 2015;5(2):557-61. http://doi.org/10.7324/JAPS.2015.58.S9

El Hilaly J, Israili ZH, Lyoussi B. Acute and chronic toxicological studies of Ajuga iva in experimental animals. J Ethnopharmacol. 2004;91(1):43-50. https://doi.org/10.1016/j.jep.2003.11.009 PMid:15036466

Li IC, Chen YL, Lee LY, Chen WP, Tsai YT, Chen CC, et al. Evaluation of the toxicological safety of erinacine A-enriched Hericium erinaceus in a 28-day oral feeding study in sprague-dawley rats. Food Chem Toxicol. 2014;70:61-7. https://doi. org/10.1016/j.fct.2014.04.040 PMid:24810469

Ilyanie Y, Wong TW, Choo CY. Evaluation of hypoglycemic activity and toxicity profiles of the leaves of Ficus deltoidea in rodents. J Complement Integr Med. 2011;8:1-16. https://doi. org/10.2202/1553-3840.1469 PMid:22754938

Okamura T, Suzuki S, Ogawa T, Kobayashi J, Kusuoka O, Hatayama K, et al. Background data for general toxicology parameters in RccHan: WIST rats at 8, 10, 19 and 32 weeks of age. J Toxicol Pathol. 2011;24(4):195-205. https://doi. org/10.1293/tox.24.195 PMid:22319231

Chanda S, Parekh J, Vaghasiya Y, Dave R, Baravalia Y, Nair R. Medicinal plants-from traditional use to toxicity assessment: A review. Int J Pharm. 2015;6(7):2652-70.

Diaz D, Hartley DP, Kemper R. Issue Investigation and Practices in Discovery Toxicology. USA: John Wiley & Sons, Inc.; 2016.

Han ZZ, Xu HD, Kim KH, Ahn TH, Bae JS, Lee JY, et al. Reference data of the main physiological parameters in control sprague-dawley rats from pre-clinical toxicity studies. Lab Anim Res. 2010;26(2):153-64. https://doi.org/10.5625/lar.2010.26.2.153

Bo L, Zhao G, Yin G, Sun H, Gao-Ling G, Yang X. Effect of breviscapine tablets on ventricular arrhythmias in hypertrophic myocardium of Rabbit Heart. J Xinxiang Med Coll. 2011;1:2154-6.

Organisation for Economic Co-operation and Development. OECD Guidelines for the Testing of Chemicals, Test No. 407: Repeated Dose 28-day Oral Toxicity Study in Rodents. Paris, France: Organisation for Economic Co-operation and Development. 2008. https://doi.org/10.1007/ springerreference_75881

Woo GH, Shibutani M, Ichiki T, Hamamura M, Lee KY, Inoue K, et al. A repeated 28-day oral dose toxicity study of nonylphenol in rats, based on the ‘Enhanced OECD Test Guideline 407’ for screening of endocrine-disrupting chemicals. Arch Toxicol. 2007;81(2):77-88. https://doi.org/10.1007/s00204-006-0129-6 PMid:16847671

Olorunnisola O, Bradley G, Afolayan A. Acute and sub-chronic toxicity studies of methanolic extract of Tulbaghia violacea Rhizomes in wistar rats. Afr J Biotechnol. 2012;11(83):14934-40.

Nugroho et al. Acute and Subchronic Toxicity of Ficus deltoidea

https://doi.org/10.5897/ajpp12.181

Balogun F, Ashafa A. Comparative study on the antioxidant activity of Dicoma anomala and Gazania krebsiana used in basotho traditional medicine. S Afr J Bot. 2015;98:170. https:// doi.org/10.1016/j.sajb.2015.03.014

Balogun SO, Damazo AS, de Oliveira Martins DT. Helicteres sacarolha A. St.-Hil. et al.: Gastroprotective and possible mechanism of actions in experimental animals. J Ethnopharmacol. 2015;166:176-84. https://doi.org/10.1016/j.jep.2015.03.021 PMid:25792014

Downloads

Published

2020-03-15

How to Cite

1.
Nugroho RA, Aryani R, Manurung H, Rudianto R, Prahastika W, Juwita A, Alfarisi AK, Pusparini NAO, Lalong A. Acute and Subchronic Toxicity Study of the Ethanol Extracts from Ficus deltoidea Leaves in Male Mice. Open Access Maced J Med Sci [Internet]. 2020 Mar. 15 [cited 2024 Nov. 23];8(A):76-83. Available from: https://oamjms.eu/index.php/mjms/article/view/3989