Authors :
Rakotoarisoa Mbolatiana Abigaila; Nomenjanahary Lalaina; Razafimanantsoa Herimamonjy; Rakotonandrasana Stephan Richard; Jeannoda Victor Louis
Volume/Issue :
Volume 11 - 2026, Issue 1 - January
Google Scholar :
https://tinyurl.com/mtwnh8mn
Scribd :
https://tinyurl.com/yk3tdtrf
DOI :
https://doi.org/10.38124/ijisrt/26jan1553
Note : A published paper may take 4-5 working days from the publication date to appear in PlumX Metrics, Semantic Scholar, and ResearchGate.
Abstract :
The RUBIACEAE family is a promising source in herbal medicine. Many of them are widely used to treat various diseases in folk medicine. This research aims to promote biodiversity in Madagascar and innovate traditional malagasy medicine. The leafy twigs of Gaertnera phanerophlebia Baker (RUBIACEAE), a species endemic to the Great Island, have been used to treat pain, fever and wounds. Until now, few studies on its pharmacological and toxicological effects have been published thus so far. So, this study aims to verify the safety of the plant extract and determine the possible side effects by comparing its acute toxicity via three different administration routes in mice. In vivo results demonstrated that the leafy twigs crude extract (ST380RF) is non-toxic and non-irritating to the skin according to the Draize index. No mortality or sever effetcs were observed with oral administration up to the maximum dose of 5,000 mg/kg of body weight. Anatomopathological studies of vital organs revealed no adverse effects. However, intraperitoneal injection of the crude extract resulted in the death of some animals, yielding an LD50 of 225,007 mg/kg of b.w, which is considered moderatly toxic according to the Hodge et Sterner classification. Additionally, macroscopic and microscopic analysis of vital organs revealed moderate changes in the spleen and kidneys. These results suggested that the oral and dermal administration of the leafy twigs of this plant appeared harmless and safe for medication. Anyway, since no data are available on the effects of repeated exposure, dermal application seems reasonable for drug development based on the crude extract.
Keywords :
Gaertnera Phanerophlebia, Leafy Twigs, Crude Extract, Acute Toxicity, Anatomopathology.
References :
- University of Wisconsin Chemical Safety and Disposal Guide (UWCSDG). Chemical and Environmental Safety Program, University of Wisconsin- Madison 30 N. Murray St., Madison, WI, 1999, 53715-2609.
- Baki MA, Khan A, Al Bari MAA, Mosaddik A, Sadik G, Mondal K. Sub-acute toxicological studies of Pongamol isolated from Pongamia pinnata. Research Journal of Medicine and Medical Sciences. 2007; 2:53-57.
- Rajeshkumar D. Evaluation of antioxidant property and toxicological assessment of Polyalthia longifolia var. Pendula leaf, thesis PhD, Saurashtra University, 2010.
- Rakotoarisoa MA, Rakotoarivelo H, Rakotonandrasana S, Rasolofomanana JR, Randriamialinoro F, Ranarivelo L, Ratsimbason M, Vahinalahaja Razafintsalama E, Ralambonirina STR. Etudes chimique et biologique de sept plantes médicinales de Madagascar de la famille RUBIACEAE. Mada-hary. 2016 ; ISSN 2410-0315, 5.
- OCDE. Replacement, Reduction, and Refinement for minimizing animal use in research and improving animal welfare. Toxicité Orale Aigüe -Méthode De L’ajustement Des Doses. In : Lignes Directrices De L’OCDE Pour Les Essais De Produits Chimiques, OCDE, Paris. 2008; 1(1):1 – 29.
- OCDE. Document d’orientation sur la reconnaissance, l'évaluation et l'utilisation des signes cliniques comme critères d'évaluation de la sécurité chez l'homme pour les animaux d'expérimentation, Série OCDE Sur Les Essais Et L'évaluation, N° 19, Éditions OCDE. Paris, 2002.
- Rakotoarisoa MA, Ralambonirina ST, Randriamialinoro F, Rakotoarisoa M, Vahinalahaja Razafintsalama E and Jeannoda V. Fractionation and bioassay-guided isolation of Loganin from the bark of Breonia perrieri Homolle, an endemic RUBIACEAE from Madagascar. Journal of Pharmacognosie and Phytochemistry. 2021; 10(4): 38-46.
- OCDE. Sous-comité d’experts du système général harmonisé de classification et d’étiquetage des produits chimiques: dangers pour la santé et l’environnement - toxicité aiguë. UN/SCEGHS/2/INF 2001, 11-13.
- OCDE. Ligne directrice de l’OCDE pour les essais de produits chimiques : toxicité orale aiguë - méthode de l’ajustement des doses. OCDE. 425, 2006, 29.
- Rakotoarisoa MA. Gastroprotective and antiulcer potential of aerial part extract of Gaertnera phanerophlebia Baker (RUBIACEAE). International Journal of Innovative Science and Research Technology. 2025 ; 10(10), 2524-2533.
- Rakotoarisoa MA, Randrianomenjanahary AR & Randrianasolo R. Herbal syrup expectorant from Allium cepa L. (LILIACEAE) and Eriobotrya japonica Lindl. (ROSACEAE). International Research Journal of Modernization In Engineering Technology and Sciences. 2025 ; 7(7), ISSN : 2582-5208.
- Dragstedt A, Lang B. Etude de la toxicité par administration unique d’un nouveau médicament. Annales Pharmaceutiques Français. 195; 11.
- Teo S, Stirling D, Thomas S, Hoberman A, Kiorpes A. A 90 days oral gavage toxicity study of D-methylphenidate and D, L-methylphenidate in Sprague-Dawley rats. Toxicology. 2002;179(3):183-196.
- Lee M, Seo C, Cha S, Sim H. Safety assessment of So cheong-ryong- tang: Subchronic toxicity study in Crl: CD Sprague Dawley rats. Molecular Medicine Reports. 2014;9:2273-2282.
- Rajemiarimoelisoa CF, Rakoto DAD, Randrianarivo HR, Jeannoda VL. Purification and toxicity study of a saponin from seeds of Albizia odorata, a FABACEAE from Madagascar. Journal of Pharmacological Sciences. 2015;3(5):264-271.
- Rakotoarisoa MA. Formulation and evaluation of an antihypertensive oral solution based on Sarongazany'Roots (CAESALPINIACEAE) from Madagascar. International Journal of Multidisciplinary Research and Publications. 2025 ; 8(6) : 228‑233.
- Loomis TA, Hayes AW. Principes de toxicologie de Loomis. 4e éd. Californie : Academic Press. 1996. pp. 208-245.
- Rakotoarisoa MA, Tohandrainy MA, Andriamanatafika T and Randrianasolo R. Safe and natural oral solid tablets antihypertensive based on Cassia occidentalis (FABACEAE). World Journal of Advanced Research and Reviews. 2026 ; 29(01) :001-016.
- Enegide C, David A, Fidelis SA. Nouvelle méthode de détermination de la toxicité aiguë chez les modèles animaux. Toxicology International. 2013;20(3):224–226.
- Tubaro A, Sosa S, Carbonatto M, Altinier G, Vita F, Melato M, Satake M, Yasumoto T. Oral and intraperitoneal acute toxicity studies of yessotoxin and homoyessotoxins in mice, Toxicon. 2003; 41(7): 783-792, ISSN 0041-0101.
- Matsumoto Y, Murakami Y, Suda K, Takahasi M, Nakai K, Ohta N & Nakamura T. L'acide éthylènediaminetétraacétique conjugué au polyéthylène glycol est un chélateur sûr pour la dénudation de l'épithélium colique et la thérapie de remplacement de l'épithélium intestinal. Scientific Reports. 2025; 15 (1): 41025.
- Greaves P. Hematopoietic and lymphatic systems. Histopathology of preclinical toxicity studies interpretation and relevance in drug safety evaluation. 2007.
- Silva MG, Aragão TP, Vasconcelos CF, Ferreira PA, Andrade BA, Costa I M & Lafayette SS. Acute and subacute toxicity of Cassia occidentalis L. stem and leaf in Wistar rats. Journal of Ethnopharmacology. 2011; 136(2): 341-346.
- Schnutenhaus S, Luthardt RG, Rudolph H, Götz W. Histological examination and clinical evaluation of the jawbone of an adult patient with cleidocranial dysplasia: a case report. International Journal of Clinical and Experimental Pathology. 2015; 8(7):8521-31.
- Vanhulle VP, Martiata GA, Verbeecka RK, Horsmansb Y, Calderona PB, Eeckhoudta SL, Tapera HS, Delzennea N. Cryopreservation of rat precisioncut liver slices by ultrarapid freezing Influence on phase I and II metabolism and on cell viability upon incubation for 24 hours. Life Sciences. 2001; 68: 2391–2403.
- Yam MF, Ang LF, Salman IM, Ameer OZ, Lim V, Ong LM & Basir R. L'extrait de feuilles d'Orthosiphon stamineus protège contre la gastropathie induite par l'éthanol chez le rat. Journal of medicinal food. 2009; 12 (5): 1089-1097.
- Meza M & Hermawati E. Dermal Acute Toxicity Test. International Journal of Social Health. 2024.3: 624-629.
- Johnson AW & Goodwin BFJ. Le test de Draize et ses modifications. Current Problems in Dermatology. 1985; 14 : 31-38.
- OCDE. Ligne directrice de l'OCDE pour les essais de produits chimiques. 2017.
- Bene K, Camara D, Soumahoro IA, Y Kanga Y. et Zirihi N. Formulation galénique d’une pommade antimicrobienne à base d’un extrait hydroalcoolique de Bersama. Ethnopharmacologia. 2017; 58: 62 – 69.
- Rakotoarisoa MA, Ralambonirina ST, Andriamamonijisoa D, Rakotoarisoa M, Jeannoda V. Pommade cicatrisante à base de Gaertnera phanerophlebia, une RUBIACEAE Malagasy. Revue de Recherche Pour de Développement, série Sciences Biologiques. 2020; CIDST n°27.
- Rakotoarisoa MA. New Anti-inflammatory Balm Based on a POACEAE Weed: Eleusine indica (L) Gaertn. International Journal of Multidisciplinary Research and Publications. 2025 ; 8(2) : 54-57, ISSN : 2581-6187.
- Djerrou Z, Djaalab H, Riachi F, Serakta M, Chettou A, Maameri Z & Hamdi-Pacha Y. Irritantcy potential and sub acute dermal toxicity study of Pistacia lentiscus fatty oil as a topical traditional remedy. African Journal of Traditional, Complementary and Alternative Medicines. 2013; 10(3): 480-489.
- Yapi AB, Etien DT, Konan KF, et Zirihi GN. Formulation galénique d’une pommade antimicrobienne à base d’un extrait hydroéthanolique de Aspilia efricana (Pers.) C.D. Adams Var. Africana, Une Plante De La Pharmacopée Africaine. European Journal Of Scientific Research. 2019; 153(2): 207-222.
- Rakotoarisoa MA & Jeannoda VL. Validation of herbal ointment wound healing efficacy formulated from Gaertnera phanerophlebia Baker. Journal of Pharmacy and Biological Sciences (IOSR-JPBS). 2025 ; 20(4), Serie 3 : 59-69.
- Riyadi PH, Susanto E, Anggo AD, Arifin MH & Rizki L. Effect of methanol solvent concentration on the extraction of bioactive compounds using ultrasonic-assisted extraction (UAE) from Spirulina platensis. Food Research. 2023; 7(3): 59-66.
- Hodge HC & Sterner JH. Determination of substance acute toxicity by LD50. American Industrial Hygiene Association Journal. 1943; 10: 93.
- Eichenbaum G, Damsch S, Looszova A, Vandenberghe J, Van den Bulck K, Roels K, et Lammens L. Impact de la procédure de dosage par gavage et du contenu gastrique sur les effets respiratoires indésirables et la mortalité dans les études de toxicité chez le rat. Journal de toxicologie appliquée. 2011; 31 (4): 342-354.
- Attah M, Jacks T, Garba SH, Dibal NI, & Ojo P. Évaluation de la toxicité orale aiguë induite par l'extrait n-hexane des feuilles de Leptadenia hastata chez les rats Wistar. International Journal of Veterinary Sciences and Animal Husbandry. 2019; 4 (1): 40-4.
- Ibrahim KE, Al-Mutary MG, Bakhiet AO, Khan HA. Histopathology of the liver, kidney, and spleen of mice exposed to gold nanoparticles. Molecules. 2018 ;23(8):1848.
- Abd RN, & Jebur AL. Effet d'Evisect sur l'indice organo-somatique et les modifications pathohistologiques de certains organes vitaux chez la souris blanche. Systematic Reviews in Pharmacy . 2020; 11 (11): 1910-1914.
- Adly F, Moussaid M, Elamrani AA, Berahal C, Moussaid H, Bourhim N and Loutfi M. Étude chimique de l’extrait aqueux d’Allium subvillosum (L.) (ALLIACEAE) et l’évaluation de sa toxicité chez les souris. International Journal of Biological and Chemical Sciences. 2015; 9 (1): 542‑51.
The RUBIACEAE family is a promising source in herbal medicine. Many of them are widely used to treat various diseases in folk medicine. This research aims to promote biodiversity in Madagascar and innovate traditional malagasy medicine. The leafy twigs of Gaertnera phanerophlebia Baker (RUBIACEAE), a species endemic to the Great Island, have been used to treat pain, fever and wounds. Until now, few studies on its pharmacological and toxicological effects have been published thus so far. So, this study aims to verify the safety of the plant extract and determine the possible side effects by comparing its acute toxicity via three different administration routes in mice. In vivo results demonstrated that the leafy twigs crude extract (ST380RF) is non-toxic and non-irritating to the skin according to the Draize index. No mortality or sever effetcs were observed with oral administration up to the maximum dose of 5,000 mg/kg of body weight. Anatomopathological studies of vital organs revealed no adverse effects. However, intraperitoneal injection of the crude extract resulted in the death of some animals, yielding an LD50 of 225,007 mg/kg of b.w, which is considered moderatly toxic according to the Hodge et Sterner classification. Additionally, macroscopic and microscopic analysis of vital organs revealed moderate changes in the spleen and kidneys. These results suggested that the oral and dermal administration of the leafy twigs of this plant appeared harmless and safe for medication. Anyway, since no data are available on the effects of repeated exposure, dermal application seems reasonable for drug development based on the crude extract.
Keywords :
Gaertnera Phanerophlebia, Leafy Twigs, Crude Extract, Acute Toxicity, Anatomopathology.