A Subchronic Toxicity Test of <i>Dillenia ochreata</i> Leaves Extract on Wistar rats



  • Muharni Muharni Department of Chemistry, Faculty of Mathematics and Natural Sciences, University of Sriwijaya, Indralaya, Ogan Ilir, South Sumatra, 30662 Indonesia
  • Nurnaili Choirunnisa Department of Pharmacy, Faculty of Mathematics and Natural Sciences, University of Sriwijaya, Indralaya, Ogan Ilir, South Sumatra, 30662 Indonesia
  • Fitrya Fitrya Department of Pharmacy, Faculty of Mathematics and Natural Sciences, University of Sriwijaya, Indralaya, Ogan Ilir, South Sumatra, 30662 Indonesia


histopathology, biochemistry, hematology, subchronic toxicity, Dillenia ochreata


Dillenia ochreata were used traditionally to treat wounds and scabies. D. ochreata leaves have also been reported to have antibacterial, anti-inflammatory, and analgesic activities. This study aimed to determine the subchronic toxicity of an ethanol extract of D. ochreata leaves in Wistar rats. Tests were performed 28 days after administration of the extract. This study used 50 rats (25 males and 25 Females), each consisting of five groups: one control group (I) and four treatment groups (II-V) with doses of 100, 200, 400 and 800 mg/kg body weight (BW). Haematological parameters, biochemistry and histopathology of the liver, kidneys and heart were evaluated. The results showed that the treatment groups' haematological levels and blood biochemical levels were still within normal, except for group V, which showed a significant difference (p <0.05) from the group I. The organ histopathology results in group V showed liver and kidney damage with fat degeneration and moderate necrosis in both male and female rats. Administration of the ethanol extract of D. ochreata leaves up to a dose of group IV showed no toxic symptoms, but toxic effects were shown at a dose of group V. The dose of 800 mg/kg BW (group V) of the ethanol extract of D. ochreata was found unsafe for use.


Sholikhah EM. Indonesian medicinal plants as sources of secondary metabolites for pharmaceutical industry. J Med Sci. 2016;48:226-239.

Alshammari TM. Drug safety: The concept, inception and its importance in patients' health. Saudi Pharm J. 2016; 24: 405-412.

Jitareanu A, Trifan A, Vieriu M, Caba I-C, Mârțu I, Agoroaei L. Current Trends in Toxicity Assessment of Herbal Medicines: A Narrative Review. Processes. 2023;11:1-83.

Yustian I, Muharni S, Zulaicha S, Arbi M. Special research on the exploration of ethnomedicine and local community medicinal plants in Indonesia (Ethnic Musi II Palembang). Ministry of Health Republic of Indonesia 2012.

Endress PK. Relationships Between Floral Organization Architecture and Pollination Mode. Plant System Evolution,1996; 206: 99-118.

Muharni M, Fitriya F, Farida S. Antibacterial assay ethanol extract Musi tribe medicinal plant in Musi Banyuasin, South Sumatra [Indonesian]. Jurnal Kefarmasian Indonesia 2017; 7: 127–135.

Muharni M, Amriani A, Fitrya F, Mukafi A. Wound healing activity of Dillenia ochreata leaves ethanol extract in Wistar rats. J Pharm Pharmacogn Res 2022; 10: 896-904.

Efdi M, Ninomiya M, Suryani E, Tanaka K, Ibrahim S, Watanabe K, Koketsu, M. Sentulic Acid: A Cytotoxic Ring A-Seco Triterpenoid from Sandoricum koetjape Merr. J Bioorganic and Med Chem Lett. 2012; 22: 4242–4245.

Kpemissi M, Metowogo K, Melila M, Veerapur VP, Negru M, Taulescu M, Potarniche AV, Suhas DS, Puneeth TA, Vijaya Kumar S, Galedbeku KE, Aklikokou K . Acute and subchronic oral toxicity assessments of Combretum micranthum (Combretaceae) in Wistar rats. Toxicol Rep. 2020; 118:162-168.

Shukla V, Asthana S, Gupta P, Dwivedi PD, Tripathi A, Das M. Toxicity of Naturally Occurring Anthraquinones. Adv Mol Toxicol. 2017;11:1-50.

Fitrya F, Fithri NA, Muharni M. A subchronic toxicity test of ethanol extract from Tunjuk langit rhizome (Helminthostachys zeylanica) on albino rats, Rattus noverticus (Wistar strain). Asian J Pharm Clin Res 2017;10:270-273.

Kanina L, Solehah M, Plumeriastuti H, Widyowati R, Wardoyo BPE. Acute and Subchronic Toxicity Assessment of 70% Ethanol Extract of Gendarusa Leaves In Vivo [Indonesian]. Jurnal Farmasi Dan Ilmu Kefarmasian Indonesia. 2022; 9:39-47.

Schmidt BM, Tameris M, Geldenhuys H, Luabeya A, Bunyasi E, Hawkridge T, MCClaim JB, Mohamed H, Scriba TJ, McShane H, Hatherill M. Comparison of haematology and biochemistry parameters inhealthy South African infants with laboratory reference interval. Trop Med Int Health. 2018; 23: 63-68.

Nadia M, Rima A, Rima R, khouloud A, Abdelouahab B.Evaluation of the Subacute Toxic Effects of the Alkaloids of the Seeds of Peganum harmala L in the Liver, Kidney and Ovary of Female Rats. Trop J Nat Prod Res. 2022; 6(10):1632-1637.

Küme T, Sağlam B, Ergon C, Sisman AR. Evaluation and comparison of Abbott Jaffe and enzymatic creatinine methods: Could the old method meet the new requirements? J Clin Lab Anal. 2018 Jan;32(1):e22168. doi: 10.1002/jcla.22168. Epub 2017 Feb 15.

Lazic SE, Semenova E, Williams DP. Determining organ weight toxicity with Bayesian causal models: Improving on the analysis of relative organ weights. Sci Rep 2020; 10: 6625

Mayanti T, Darwati D, Al Anshori J, Supratman U, Madihah M, Lesmana R, Dinata DI, Gaffar S. Toxicity Evaluation of Ethanol Extract of Lansium domesticum cv kokossan Seeds in Female Wistar Rats. Trop J Nat Prod Res. 2020; 4(8):348-354.

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.

Nalimu F, Oloro J, Peter EL, Ogwang PE. Acute and sub-acute oral toxicity of aqueous whole leaf and green rind extracts of Aloe vera in Wistar rats. BMC Complement Med Ther 2022; 22: 1-14.

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): 2652-2670.

Delwatta SL, Gunatilake M, Beuman V, Seneviratne MD, Dissanayaka MLB, Batagoda SS et al. Reference values for selected haematological, biochemical and physiological parameters of Sprague‐Dawley rats at the Animal House, Faculty of Medicine, University of Colombo, Sri Lanka. Animal Model Exp Med. 2018; 1: 250–4.

Douglas JW, Wardrop KJ. Schalm’s Veterinary Hematology. 6th ed. Wiley-Blackwell; 2010: 852-887 p.

Holopainen S, Laurila HP, Lappalainen AK, Rajamäki MM, Viitanen SJ. Polycythemia in dogs with chronic hypoxic pulmonary disease. J Vet Intern Med 2022; 36:1202-1210.

Tigner A, Ibrahim SA, Murray IV. Histology, White Blood Cell. StatPearls Publishing; 2022. Available from: https://www.ncbi.nlm.nih.gov/books/NBK563148/

Warditiani NK, Sari PMNA, Yustiantara PS, Wirasuta IMAG. Acute and Sub-Acute Oral Toxicity Profile of Purified Tomato Extract on the Liver and Kidney Functions of Male Wistar Rats. Trop J Nat Prod Res. 2021; 5(11):1962-1965.

Giknis M L, Clifford CB. Clinical Laboratory Parameters for Crl: Wl(Han), Charles River Laboratories, Canada. 2008

Sukandar EY, Sheba SH. Acute and Sub-chronic Toxicity Studies of Combination of Physalis angulata L. (Cecendet) Extract and Methylprednisolone on Animals. Int J Integr Health Sci. 2019: 7: 48-55.

Alimuddin A, Murtini S, NurhayatiS. Behaviour, Histopathology and Physiological Responses of Rat Fed Diets Containing Growth Hormone Transgenic Fish Meal. Hayati J Biosci. 2019; 26: 1-6.

Liu W, Du JJ, Li ZH, Zhang XY, Zuo HD. Liver injury associated with acute pancreatitis: The current status of clinical evaluation and involved mechanisms. World J Clin Cases. 2021; 9: 10418-29.

Sharma A, Hirulkar NB, Wadel P, Das P. Influence of Hyperglycemia on Renal Function Parameter in Patients with Diabetes Mellitus. IJPBA 2011; 2(Suppl 2): 734–739.

Schoeffner DJ, Warren DA, Muralidhara S. Bruckner JV, Simmons JE. Organ Weights and Fat Volume in Rats As a Function of Strain and Age. J Toxicol Environ Health. 1999; 56: 449-62.

Yan Y, Yong Z, Chunying L, Yushi Z, Yang B, Yalan Y, et al. Toxicity study of ethanol extract from Oroxylumindicum (L.) Vent in rats. J Tradit Chin Med. 2018; 38(5): 714-725

Weidemann DK, Weaver VM, Fadrowski JJ. Toxic environmental exposures and kidney health in children. Pediatr Nephrol. 2016;31:2043-2054.

Westbrook RH, Dusheiko G, Williamson. Pregnancy and Liver Disease, J Hepatol 2016; 64: 933-45.

Mahadevan V. Anatomy of the live. Surgery (Oxford) 2020; 38: 427-431.

Jung J, Ryu S, Ki IA, Woo HA, Lee K. Some Biological Consequences of the Inhibition of Na, K-ATPase by Translationally Controlled Tumor Protein (TCTP). Int J Mol Sci. 2018 4;19:1657.

Puteri FH, Widjaja J, Cahyani F, Mooduto L, Wahjuningrum DA. The comparative toxicity of xanthones and tannins in mangosteen (Garcinia mangostana Linn.) pericarp extract against BHK-21 fibroblast cell culture. Contemp Clin Dent 2019;10:319-23.

Arthur FKN, Woode E, Terlabi EO, Larbie C. Evaluation of acute and subchronic toxicity of Annona Muricata (Linn.) aqueous extract in animals. Eur J Exp Biol. 2011;1(Suppl 4):115– 124.

Alshalani A, Acker JP. Red blood cell membrane water permeability increases with length of ex vivo storage. Cryobiology. 2017;76:51-58.

Lasrado N, Jia T, Massilamany C, Franco R, Zsolt Illes Z, and Reddy. Mechanisms of sex hormones in autoimmunity: focus on EAE. Biol Sex Differ. 2020; 11:50



How to Cite

Muharni, M., Choirunnisa, N., & Fitrya, F. (2023). A Subchronic Toxicity Test of <i>Dillenia ochreata</i> Leaves Extract on Wistar rats: http://www.doi.org/10.26538/tjnpr/v7i11.32. Tropical Journal of Natural Product Research (TJNPR), 7(11), 5244–5249. Retrieved from https://tjnpr.org/index.php/home/article/view/3038