South Asian Research Journal of Natural Products

Phytochemical Characterization and Acute Toxicity Investigation of the Hydroethanolic Leaf Extract of Dacryodes edulis (G. Don) H.J. Lam on Wistar Rat Models

Nomo Honore

Department of Biochemistry, Faculty of Science, University of Yaoundé 1, Cameroon.

Tembe Estella Fokunang *

Department of Pharmacotoxicology and Pharmacokinetics, Faculty of Medicine & Biomedical Sciences, University of Yaoundé 1, Cameroon.

Bayaga Herve

Department of Pharmacotoxicology and Pharmacokinetics, Faculty of Medicine & Biomedical Sciences, University of Yaoundé 1, Cameroon.

Njinkio Nono Borgia

Department of Pharmacotoxicology and Pharmacokinetics, Faculty of Medicine & Biomedical Sciences, University of Yaoundé 1, Cameroon.

Mbacham Wifred

Department of Biochemistry, Faculty of Science, University of Yaoundé 1, Cameroon.

Charles Fokunang

Department of Pharmacotoxicology and Pharmacokinetics, Faculty of Medicine & Biomedical Sciences, University of Yaoundé 1, Cameroon.

*Author to whom correspondence should be addressed.

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Abstract

Medicinal plants play an important role in the management of several diseases and have become widespread. However, people use plant species without considering the toxicity they may present. In a previous study, the hydroethanolic leaf extract of D edulis showed a very good anti-ulcer activity (86% protection rate). The aim of this study was to evaluate the phytochemical composition and to investigate the acute toxicity of this extract on zootechnical, biochemical and histological parameters in Wistar rats.

 Fresh leaves of Dacryodes edulis were collected in Yaoundé, Cameroon and a qualitative and quantitative phytochemical assessment was carried out using the methods described by Harbone. Then the acute toxicity was tested according to Organization for Economic Co-operation and Development (OECD) guideline 423, by forming 2 experimental groups of 10 animals each (5 males and 5 females): Group I (Control), which received 2 mL of physiological saline solution (SSF 0.9%), Groups II, which received the hydro-ethanolic leaf extract of D. edulis in a single dose of 2000 mg/kg. The zoophysical behaviour of the animals was observed for 14 days and on the 14th day of exposure, biochemical (Protein, creatinine, ALT, and AST) and histopathological parameters of the liver and kidney were measured.

Several primary metabolites including total polyphenols, tannins, coumarins, flavonoids, betacyans were identified, anthraquinones, cardiac glycosides and ascorbic acid.  Furthermore, the extract did not cause any pathological changes as revealed by the biochemical markers of the organs whose functions were evaluated, and the histological analysis showed a normal organ architecture when compared to controls. The hydro-ethanolic extract was therefore relatively safe and without toxic effects according to the parameters tested at the dose of 2000 mg/kg.

Keywords: Dacryodes edulis, phytochemicals, acute toxicity, liver, kidneys

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References

Yuan H, Ma Q, Ye L, Piao G. The Traditional Medicine and Modern Medicine from Natural Products. Molecules [Internet]. 2016 [cité 10 nov 2022];21 (5):559. Availbale:https://www.mdpi.com/1420-3049/21/5/559

Mythilypriya R, Shanthi P, Sachdanandam P. Oral Acute and Subacute Toxicity Studies with Kalpaamruthaa, a Modified Indigenous Preparation, on Rats. Journal of Health Science. 2007;53(4): 351‑8.

Han CT, Kim MJ, Moon SH, Jeon YR, Hwang JS, Nam C, et al. Acute and 28-Day Subacute Toxicity Studies of Hexane Extracts of the Roots of Lithospermum erythrorhizon in Sprague-Dawley Rats. Toxicological Research [Internet]. 2015 [cité 10 nov 2022];31(4):403‑14. Availbale:http://koreascience.or.kr/article/JAKO201502150665866.page

Li Y, Kandhare AD, Mukherjee AA, Bodhankar SL. Acute and sub-chronic oral toxicity studies of hesperidin isolated from orange peel extract in Sprague Dawley rats. Regulatory Toxicology and Pharmacology [Internet]. 1 juill 2019 [cité 10 nov 2022];105:77‑85. Availbale:https://www.sciencedirect.com/science/article/pii/S0273230019300923

Aydιn A, Aktay G, Yesilada E. A Guidance Manual for the Toxicity Assessment of Traditional Herbal Medicines. Natural Product Communications [Internet]. 1 nov 2016 [cité 10 nov 2022];11(11):1934578X1601101131. Availbale:https://doi.org/10.1177/1934578X1601101131

Araújo MC de PM, Barcellos NMS, Vieira PM de A, Gouveia TM, Guerra MO, Peters VM, et al. Acute and sub chronic toxicity study of aqueous extract from the leaves and branches of Campomanesia velutina (Cambess) O. Berg. Journal of Ethnopharmacology [Internet]. 6 avr 2017 [cité 10 nov 2022];201:17‑25. Availbale:https://www.sciencedirect.com/science/article/pii/S0378874116315410

Hazarika I, Geetha KM, Sundari PS, Madhu D. Acute oral toxicity evaluation of extracts of Hydrocotyle sibthorpioides in wister albino rats as per OECD 425 TG. Toxicology Reports [Internet]. 1 janv 2019 [cité 10 nov 2022];6:321‑8. Availbale:https://www.sciencedirect.com/science/article/pii/S2214750019300411

Han JS, Lee BS, Han SR, Han HY, Chung MK, Min BS, et al. A subchronic toxicity study of Radix Dipsaci water extract by oral administration in F344 rats. Regulatory Toxicology and Pharmacology [Internet]. 1 nov 2016 [cité 10 nov 2022];81:136‑45. Availbale:https://www.sciencedirect.com/science/article/pii/S0273230016302070

Balogun FO, Tom Ashafa AO. Acute and Subchronic Oral Toxicity Evaluation of Aqueous Root Extract of Dicoma anomala Sond. in Wistar Rats. Evidence-Based Complementary and Alternative Medicine [Internet]. 13 avr 2016 [cité 10 nov 2022]; 2016:e3509323. Availbale:https://www.hindawi.com/journals/ecam/2016/3509323/

Onana JM. A synoptic revision of Dacryodes (Burseraceae) in Africa, with a new species from Central Africa. Kew Bull [Internet]. 1 sept 2008 [cité 10 nov 2022];63(3):385‑400. ‘Availbale:https://doi.org/10.1007/s12225-008-9064-4

Tee LH, Yang B, Nagendra KP, Ramanan RN, Sun J, Chan ES, et al. Nutritional compositions and bioactivities of Dacryodes species: A review. Food Chemistry [Internet]. 15 déc 2014 [cité 10 nov 2022];165:247‑55. Availbale:https://www.sciencedirect.com/science/article/pii/S0308814614008000

Olivier TT, Moïse F, Jackson SA, Francis NT. A review on traditional uses, phytochemical and pharmacological profiles, spiritual and economic values, and toxicity of dacryodes edulis (G. DON) H.J. LAM. Journal of Drug Delivery and Therapeutics [Internet]. 12 sept 2016 [cité 19 juin 2021];6(5):84‑90. Disponible sur: http://www.jddtonline.info/index.php/jddt/article/view/1276

Dacryodes edulis (G.Don) H.J.Lam [Internet]. [cité 29 oct 2022]. Availbale:https://www.prota4u.org/database/protav8.asp?fr=1&g=pe&p=Dacryodes+edulis+(G.Don)+H.J.Lam

Jirovetz L, Buchbauer G, Stoyanova AS, Georgiev EV, Damianova ST. Composition, Quality Control, and Antimicrobial Activity of the Essential Oil of Long-Time Stored Dill (Anethum graveolens L.) Seeds from Bulgaria. J Agric Food Chem [Internet]. 1 juin 2003 [cité 10 nov 2022];51(13):3854‑7. Availbale:https://doi.org/10.1021/jf030004y

Wego Kamgaing MT, Mvondo MA, Poualeu Kamani SL, Minko Essono S, Wansi Ngnokam SL. The Aqueous Extract of Dacryodes edulis (Burseraceae) Leaves Inhibits Cell Proliferation Induced by Estradiol on the Uterus and Vagina of Ovariectomized Female Wistar Rats. Advances in Pharmacological and Pharmaceutical Sciences [Internet]. 21 nov 2020 [cité 15 sept 2021]; 2020:e8869281. Availbale:https://www.hindawi.com/journals/aps/2020/8869281/

Aponjolosun BS, Fasola TR. Phytochemical, Antimicrobial and Toxicity Assessment of Dacryodes edulis (G. Don.) H. J. Lam. Leaf Extracts. African Journal of Biomedical Research [Internet]. 31 janv 2022 [cité 19 juin 2022];25(1):101‑6. Availbale:http://ojshostng.com/index.php/ajbr/article/view/227

Ononamadu CJ, Alhassan AJ, Ibrahim A, Imam AA, Ihegboro GO, Owolarafe TA, et al. Methanol-Extract/Fractions of Dacryodes edulis Leaves Ameliorate Hyperglycemia and Associated Oxidative Stress in Streptozotocin-Induced Diabetic Wistar Rats. J Evid Based Complementary Altern Med [Internet]. 1 janv 2019 [cité 7 sept 2021];24:2515690X19843832. Availbale:https://doi.org/10.1177/2515690X19843832

Erukainure OL, Mopuri R, Oyebode OA, Koorbanally NA, Islam MdS. Dacryodes edulis enhances antioxidant activities, suppresses DNA fragmentation in oxidative pancreatic and hepatic injuries; and inhibits carbohydrate digestive enzymes linked to type 2 diabetes. Biomedicine & Pharmacotherapy [Internet]. 1 déc 2017 [cité 6 juin 2022]; 96:37‑47. Availbale:https://www.sciencedirect.com/science/article/pii/S0753332217329736

Ononamadu CJ, Alhassan AJ, Ibrahim A, Imam AA, Ihegboro GO, Owolarafe AT, et al. Toxicological study of aqueous-methanol solvent fraction of methanol extract of Dacryodes edulis leaves. Toxicol Rep. 2020;7:909‑18.

Ufelle S, Ukaejiofo E, Achukwu P, Eluke B, Ghasi S, Neboh E. Potential Haemopoietic Effects of Dacryodes Edulis Seeds Extract in Wistar Rats. 2015;3: 2348‑5728.

Marcano L, Hasenawa D. Analysis of phytochemicals in leaves and seeds. Agronomy Journal. 1991;83:445‑52.

Harborne AJ. Phytochemical Methods A Guide to Modern Techniques of Plant Analysis. Springer Science & Business Media.1998;504.

OECD. Test No. 423: Acute Oral toxicity - Acute Toxic Class Method [Internet]. Paris: Organisation for Economic Co-operation and Development; 2002 [cité 10 mars 2023]. Availbale:https://www.oecd-ilibrary.org/ environment/test-no-423-acute-oral-toxicity-acute-toxic-class-method_9789264071001-en

Papanicolaou (PAP) Staining : Introduction, Principle, Procedure and Interpretation - Laboratoryinfo.com [Internet]. 2021 [cité 13 nov 2022]. Availbale:https://laboratoryinfo.com/papanicolaou-pap-staining-principle-procedure-interpretation/

Michałowicz J, Duda W. Phenols – Sources and Toxicity; 16.

Kim HY, Zuo G, Lee SK, Lim SS. Acute and subchronic toxicity study of nonpolar extract of licorice roots in mice. Food Sci Nutr. 2020;8(5):2242‑50.

Rojas-Armas J, Arroyo-Acevedo J, Ortiz-Snchez M, Palomino-Pacheco M, Castro-Luna A, Ramos-Cevallos N, et al. Acute and Repeated 28-Day Oral Dose Toxicity Studies of Thymus vulgaris L. Essential Oil in Rats. Toxicological Research [Internet]. 15 juill 2019 [cité 13 nov 2022];35 (3):225‑32. Availbale:http://www.toxicolres.org/journal/view.html?doi=10.5487/TR.2019.35.3.225

Araújo MC de PM, Barcellos NMS, Vieira PM de A, Gouveia TM, Guerra MO, Peters VM, et al. Acute and sub chronic toxicity study of aqueous extract from the leaves and branches of Campomanesia velutina (Cambess) O. Berg. Journal of Ethnopharmacology [Internet]. 6 avr 2017 [cité 13 nov 2022];201:17‑25. Availbale:https://www.sciencedirect.com/science/article/pii/S0378874116315410

Lee MY, Shin IS, Seo CS, Kim JH, Han SR, Shin HK. Subchronic oral toxicity studies of the traditional herbal formula Bangpungtongseong-san in Crl: CD (SD) rats. Journal of Ethnopharmacology [Internet]. 18 déc 2012 [cité 13 nov 2022]; 144(3):720‑5. Availbale:https://www.sciencedirect.com/science/article/pii/S0378874112006915

Teo S, Stirling D, Thomas S, Hoberman A, Kiorpes A, Khetani V. A 90-day oral gavage toxicity study of d-methylphenidate and d,l-methylphenidate in Sprague–Dawley rats. Toxicology [Internet]. 15 oct 2002 [cité 13 nov 2022];179(3):183‑96. Availbale:https://www.sciencedirect.com/science/article/pii/S0300483X02003384

Thanabhorn S, Jaijoy K, Thamaree S, Ingkaninan K, Panthong A. Acute and subacute toxicity study of the ethanol extract from Lonicera japonica Thunb. J Ethnopharmacol. 2006;107(3):370‑3.

Ononamadu CJ, Alhassan AJ, Ibrahim A, Imam AA, Ihegboro GO, Owolarafe AT, et al. Toxicological study of aqueous-methanol solvent fraction of methanol extract of Dacryodes edulis leaves. Toxicol Rep. 2020;7:909‑18.

Joseph IE, Jaja IF, Boyi AH, Olugbenga OM. Comparative effects of methanol and oil extracts of Ocimum gratissimum on testicular morphology and epididymal sperm reserve of adult male albino rats (Wistar strain). Toxicology Reports [Internet]. 1 janv 2019 [cité 14 nov 2022];6: 1127‑34. Availbale:https://www.sciencedirect.com/science/article/pii/S2214750019301301

Airaodion A, John A, Ogbuagu E, Atiba F, Olawoyin D. Nephro and Hepatotoxic Effect of Air-Freshener in Wistar Rats. 2020;1‑9.

Airaodion A, Ogbuagu E, Ogbuagu U, Odefemi A, Agunbiade A, Airaodion E. Hepatoprotective Effect of Parkia biglobosa on Acute Ethanol-induced Oxidative Stress in Wistar Rats. 2019; 2:1‑11.

Airaodion A, Ngwogu A, Ekenjoku J, Ngwogu K. Hepatoprotective Potency of Ethanolic Extract of Garcinia kola (Heckel) Seed against Acute Ethanol-Induced Oxidative Stress in Wistar Rats. 2020;1-10.

Ogbuagu E, Airaodion A, Ogbuagu U, Airaodion E. Prophylactic Propensity of Methanolic Extract of Vernonia amygdalina Leaves against Acute Ethanol-Induced Oxidative Stress in Wistar Rats. 2019;11:37-46.

Ogbuagu E, Unekwe P, Airaodion A, Nweke I, Ogbuagu U. Hepatotoxic effect of Xylopia aethiopica Fruit in Wistar Rats. 2021;1-16.

Yuet Ping K, Darah I, Chen Y, Sreeramanan S, Sasidharan S. Acute and Subchronic Toxicity Study of Euphorbia hirta L. Methanol Extract in Rats. BioMed Research International [Internet]. 10 déc 2013 [cité 10 nov 2022];2013: e182064. Availbale:https://www.hindawi.com/journals/bmri/2013/182064/

Akunne PN, Orhue NEJ. Investigation of the toxicity of aqueous and methanol extracts of Dacryodes edulis seed on Wistar rats. International Journal of Science Academic Research. 2021;5:2.

Silva-Correa CR, Villarreal-La Torre VE, González-Siccha AD, Cruzado-Razco JL, González-Blas MV, Sagástegui-Guarniz WA, et al. Acute toxicity of aqueous extract of Ambrosia arborescens Mill. on biochemical and histopathological parameters in rats. Toxicol Res [Internet]. 1 avr 2022 [cité 10 nov 2022];38(2):225‑33. Availbale:https://doi.org/10.1007/s43188-021-00106-0

Neergheen-Bhujun VS. Underestimating the Toxicological Challenges Associated with the Use of Herbal Medicinal Products in Developing Countries. Bio Med Research International [Internet]. 19 sept 2013 [cité 10 nov 2022];2013:e804086. Availbale:https://www.hindawi.com/journals/bmri/2013/804086/