Skip to main content

Toxicological evaluation of Hydrocotyle bonariensis Comm. ex Lamm (Araliaceae) leaves extract



The present study was designed to determine the cytotoxic, acute and sub-chronic oral toxicity profile of the hydroethanol extract of Hydrocotyle bonariensis leaves. The toxicity studies are preceded by a phytochemical screening to characterize the phytochemical compounds contained in this extract.


The phytochemical screening allowed to identify the presence of alkaloids, tannins, flavonoids and saponosids. The cytotoxicity study allowed retaining that this extract does not present cellular toxicity. The acute oral toxicity study was performed at a limit dose of 5000 mg/kg body weight by the oral route. The extract showed no signs of toxicity or mortality during the 14-day daily observation period. Repeated-dose oral toxicity studies were conducted by administering 500 mg/kg and 1000 mg/kg body weight of the extract orally daily to the treated batches for 28 days. The extract did not reveal any toxicity either on the weights of the animals or on the relative weights of the organs taken. The analysis of biochemical and hematological parameters revealed no significant difference between the indicators of the batches treated with 500 mg/kg and 1000 mg/kg, compared to the control batch during the 28 days of treatment.


These results show that the hydroethanol extract of Hdrocotyle bonariensis leaves is relatively safe toxicologically when administered orally.

1 Background

Plants are a valuable source of life support within the animal kingdom as they serve as sustenance, therapeutic substance and shelter material. Nearly 80% of people in developing countries use plants to treat themselves [40]. These medicinal plants are thus widely used and can also be important resources for new substances with therapeutic potential and high costs. The obvious interest in the frequent use of these medicinal plants calls for the notion of toxicity, which is defined as the set of harmful effects caused by a substance introduced at a single relatively high dose or at small doses repeated for a long time on a living organism [7, 16]. The study of the toxicity of a substance is the set of pharmacological tests, which determine the degree or harmfulness of the latter in order to regulate its use. Hydrocotyle bonariensis Comm. ex Lam. is one of the medicinal plants of the Araliaceae family, which is highly valued in the traditional treatment of several pathologies in Africa, Asia and South America. Practitioners of traditional Togolese medicine to treat mainly high blood pressure and diabetes use it. It is also used as a sedative, for kidney and liver problems, tuberculosis, rheumatoid arthritis and many other ailments [5]. Some pharmacological studies of this plant have revealed its anti-oxidant and anti-inflammatory properties [24]. Despite the wide use of H. bonaniensis in Africa, Asia and South America, this plant has not yet been the subject of scientific studies of its toxicity, allowing allowing the regulation of its use. There is no sufficient scientific data, collected based on experimental studies on this plant, to analyze its toxicological impact. The multiplicity of its virtues as well as its large geographical distribution would increase the frequency of its use and consequently would make a significant part of the population susceptible to the potential risk of toxicity linked to its use. The objectives were to (1) determine the qualitative composition of secondary metabolites of H. bonariensis, (2) evaluate the cytotoxicity on cepid larvae (Artemia salina LEACH), (3) evaluate the acute toxicity and (4) the subacute toxicity of this extract in Sprague Dawlay rats.

2 Methods

2.1 Plant material

The leaves of Hydrocotyle bonariensis were collected at the test station of the higher school of agronomy of Lome University. They were identified at the Laboratory of Botany and Plant Ecology of the Faculty of Sciences where the sample was deposited under the number ''TG 15,183''. These leaves were washed with tap water and then dried under air conditioning at 20 °C.

2.2 Preparation of the hydro-ethanolic extract

The leaves of Hydrocotyle bonariensis after 3 weeks of drying were pulverized and then 320 g were macerated for 72 h with intermittent stirring in a hydro-ethanolic solvent in a ratio of equal volumes (1:1). After maceration, the solution was filtered through filter paper and cotton. The filtrate obtained was evaporated under vacuum using a rotavapor at 45 °C. 68.28 g of extract was obtained, giving a yield of 21.34%. The extract obtained was kept in a cool place for the preparation of the different concentrations to be used in the tests.

2.3 Animal material

The animals used for the experiments are Sprague Dawlay (SD) rats of average body weight of 250 g ± 20 coming from the animal house of the Physiology-Pharmacology laboratory of the Faculty of Science of the University of Lome. They were fed a standard diet and maintained at 24 ± 2 °C, and subjected to a 12 h light/dark cycle with free access to food and water. Twelve hours before experimentation, food was removed but water remained available.

2.4 Phytochemical screening

Qualitative phytochemical screening was performed on hydroetanolic extract of Hydrocotyle bonariensis leaves (HEHBL), using the standard method based on staining and precipitation reactions as described by Houghton and Raman [17]. Table 1 shows the different chemical groups sought and the tests for their detection.

Table 1 Chemical compounds sought in the hydroalcoholic extract of H. bonariensis

2.5 Evaluation of cellular toxicity

The cytotoxicity test, based on the survival of shrimp larvae (Artemia salina LEACH) in seawater in the presence of the test solution, which was performed following the protocol adopted by Djengue et al. [8]. A. salina eggs were cultured in an Erlenmeyer flask containing seawater collected from the sea of Togolese coastline and filtered before use [27]. The whole set was left in continuous agitation for 48 h. During this time, the eggs hatched into young larvae. A stock solution of the HEHBL was prepared at a concentration of 50 mg/ml of distilled water. A series of 10 successive 1:2 dilutions were made with seawater from the stock solution of the extract. The concentrations expressed in mg/ml of the dilutions contained in test tubes numbered 1–10 were 25 mg/ml; 12.5 mg/ml; 6.25 mg/ml; 3.125 mg/ml; 1.582 mg/ml; 0.781 mg/ml; 0.391 mg/ml; 0.195 mg/ml; 0.098 mg/ml; 0.049 mg/ml respectively. Using a cone micropipette, a colony of 16 live larvae was brought into contact with the series of solutions of progressive concentrations of the HEHBL. These media and controls were left under agitation and live larvae are counted 24 h after incubation. To ensure that the death observed in the assays is attributed solely to the extract concentrations and not to starvation, these tubes are compared to control tubes containing larval solutions only knowing that A. salina shrimp larvae can live up to 48 h without food due to feeding on their yolk sac [28]. The experiment was repeated three times.

The percent mortality of shrimp larvae of each concentration of HEHBL was determined. For each sample, the lethal concentration that causes 50% larval death (LC50) was calculated with a 95% confidence interval by regression and logarithmic analysis. This value is obtained from the best fit curve giving the concentration equivalent to the death of half of the larvae. The degree of toxicity of the extract was evaluated based on the correspondence table established by Mousseux [26] (Table 2) and used by Houmènou et al. [18].

Table 2 Correspondence between LC50 and toxicity [26]

2.6 Acute toxicity

Acute test: The acute test was conducted using the OECD 425 (2008) "dose adjustment" method at 5000 mg/kg of HEHBL. The test was performed on 6 female SD rats and their behavior was observed as well as the number of deaths over a period of 14 days. After 15 h of fasting, they were divided as follows: control lot consisting of three females receiving distilled water at 10 ml/kg; experimental lot consisting of three females receiving the extract at 5000 mg/kg. Behavioral observation was performed 3 h after administration of the substances. Afterwards, hydration and feeding were performed daily for 14 days. During this period, signs of toxicity were noted, including changes in coat, motility, tremors, mass, grooming, respiration, stool appearance, mobility and death.

2.7 Subacute toxicity

The study was conducted according to OECD guideline 407 (2008). It was conducted on 18 female SD rats divided into three equal batches of 6 rats as follows: batch I, receiving distilled water at a rate of 1 ml/100 mg body weight (control batch); batches II and III receiving a solution of the HEHBL at a rate of 500 and 1000 mg/kg body weight respectively. The treatment lasted 28 days. Rats were fed and hydrated ad libitum and weighed every 2 days. At the end of the treatment, the rats were fasted for 24 h, and then blood was drawn, followed by dissection after administration of 80% ethyl urethane at 1.5 mg/kg. The organs collected were liver, kidney, spleen and heart. These were rinsed with 0.9% saline and weighed. The relative weight of each organ was calculated according to the formula: ((Pr: relative organ weight (g/100 g); Po: organ weight (g); Pa: rat body weight (g). Pr = Po/Pa X 100). Several biochemical and hematological parameters were determined.

2.8 Statistical analysis

The results are expressed as mean ± standard error on the mean. They are processed with GraphPad Prism 7.0 software. Analysis of variance (ANOVA) is used to compare the means. The results are significant if the p value < 0.05.

3 Results

3.1 Phytochemical screening of HEHBL

Qualitative tests for the determination of chemical compounds show the presence of flavonoids, alkaloids, saponosides and tannins in HEHBL (Table 3).

Table 3 Chemical compounds contained in the hydroethanolic extract of H. bonariensis

3.2 Evaluation of cytotoxicity of HEHBL

The analysis of LC50 values allows us to say that HEHBL is non-cytotoxic because the average lethal concentration (LC50) obtained is 0.12 mg/ml, higher than the limit set (0.1 mg/mL).

3.3 Assessment of acute toxicity

Oral administration of HEHBL did not result in the death of rats in all treated batches. Observations revealed no signs of asthenia, somnolence, anorexia, diarrhea or reduced mobility during the experimental period. The lethal dose 50 (LD50) is therefore assumed to be greater than 5000 mg/kg (Table 4).

Table 4 Observed parameters during the assessment of acute toxicity

3.4 Evaluation of sub-chronic toxicity

3.4.1 Body weight changes in rats

As shown in Table 5 the body weights of rats that received HEHBL at 500 mg/kg and 1000 mg/kg orally for 28 days continued to increase normally each week until day 28 of treatment in proportion to the control rats. But no significant difference was observed in comparison to the body weight of treated rats to control rats from D0 to D28.

Table 5 Average weight of rats per week

3.4.2 Relative organ weights

The results obtained are presented in Fig. 1. It appears from this figure that HHEHB at doses of 500 mg/kg and 1000 mg/kg does not significantly influence the relative weights of noble organs (heart, liver, spleen, kidneys).

Fig. 1
figure 1

Relative organ weight compared by ANOVA 2-WAYS followed by Turkey’s Test (n = 6)

3.4.3 Effects of the extract on biochemical and hematological parameters

Analysis of biochemical and hematological parameters revealed no significant difference between the indicators of the batches treated with 500 mg/kg and 1000 mg/kg, compared to the control batch during the 28 days of treatment (Table 6). However, the liver function tests (SGOT, SGPT, ALP) showed a slight increase in plasma SGOT and SGPT levels at the 1000 mg/kg dose. The analysis of nephrological parameters showed no significant change between the treated and control batches. EHEHB did not induce any significant change in creatinine and urea concentration. Oral administration of the extract days did not induce any significant change in the hematological status in the groups of rats treated at the different doses compared to the control except for a slight increase in the serum white blood cell count at the 500 mg/kg and 1000 mg/kg dose.

Table 6 Results of biochemical and hematological parameters

4 Discussion

The phytochemical screening of HEHBL revealed the presence of several phytochemical compounds. These include flavonoids, tannins, alkaloids, and saponosides. Previous studies have also revealed similar observations by noting the presence of alkaloids, flavonoids, tannins, phenolic compounds, and saponins in an extract of leaves collected in Nigeria, followed by the isolation of five terpenoid saponins from the underground part of this plant [2], [24], [38]. The secondary metabolites identified in EEHBL are endowed with a multiplicity of biologically active properties: Alkaloids have several biological properties including antibiotic, antiparasitic, anesthetic, antitumor, anticancer, analgesic, and spasmolytic properties [33] [4]. Tannins have a therapeutic action related to astringency, antibacterial, antiviral, antifungal, antiseptic, antioxidant and hemostatic actions [19, 41]. As for flavonoids, they have anti-inflammatory properties, hepatoprotective of a good blood circulation. They have a strong antioxidant or anti-radical, antiproliferative and anti-carcinogenic potential [12] and diuretic [35, 36]. Saponosides have surfactant, antifungal, antibacterial and antiviral properties, they exhibit vein and capillary protective activities and then edematous activity with hormonal activity [23]. The richness of secondary metabolites of H. bonariensis could explain the wide spectrum of its medicinal use and scientifically proven pharmacological properties [1, 10, 11, 13, 25, 29, 32]. The results of the cell toxicity test applied on Artemia salina shrimp larvae revealed variability in lethality rate, observed according to the different concentrations used. The LC50 lethal concentration determined using the polynomial and logarithmic regression curve equations highlights the fact that HEHBL does not exhibit cellular toxicity. Our results are similar to other cytotoxicity studies performed on medicinal plants [6, 18]. The results obtained from the acute toxicology study imply that the LD50 of HEHBL is greater than 5000 mg/kg body weight. According to the 2008 OECD Globally Harmonized Classification System, this extract can be classified as Category 5 and considered a non-toxic substance by the oral route. This high LD50 limit would indicate a wide margin of safety for consumption of this plant. As showed by our results, similar studies revealed the acute non-toxicity of medicinal plant extracts taken orally [21, 31]. Since no toxic effects were observed in the acute study, an additional study was conducted to evaluate the sub-chronic toxicity of HEHBL during a 28-day experiment. One of the key indicators in toxicity studies of bioactive substances is the change in body weights of treated subjects. Weight loss or gain is thought to be a consequence of the disruption of carbohydrate, protein or fat metabolism by these treatment products [20]; [39]. No significant changes in body weight were observed in rats treated with 500 mg/kg and 1000 mg/kg compared to the control after daily treatment for 28 days. This allows us to suggest that oral and sub-chronic administration of HEHBL has no effect on the normal growth of rats. Similarly, administration of the extract had no effect on the normal growth of the liver, kidney, spleen and heart as no significant changes were observed in the weight of these organs. Relative organ weights are considered to be a relatively sensitive indicator in toxicity studies [22]. The liver and kidney are essential in the evaluation of the toxicity of drugs and plant extracts because the liver and kidney are respectively responsible for the metabolism and elimination of any bioactive substance administered to a living organism. The liver has the role of detoxification of the organism, whether the toxins are of internal or external origin, while the kidney has the role of purification of the blood and elimination of waste products [3, 9, 37]. Thus, hematological and biochemical analyses were carried out to evaluate the possible alterations of the hepatic and renal functions caused by the ingestion of the extracts. Subchronic administration of HEHBL at 500 mg/Kg and 1000 mg/kg did not result in any significant changes in biochemical and hematological parameters. However, the slight increase in serum SGOT and SGPT levels at 1000 mg/kg may reflect the onset of damage to at least one of the tissues such as cardiac tissue, hepatopathy, muscular dystrophy, and internal organ damage at this dose. Renal dysfunction can be assessed by simultaneous measurements of urea, creatinine, considered the main markers of nephrotoxicity [9], [20], [14, 34]. In the present study, there were no changes in plasma urea and creatinine levels in rats treated with 500 mg/kg and 1000 mg/kg. Analysis of hematological parameters is relevant because it provides information on hematopoietic function (assessment of myeloid lineage cells), on the occurrence of allergy (white blood cell studies) and on intravascular effects such as hemolysis [15], [30]. The hematological workup showed no significant difference between treated and control rats. However, the slight increase in white blood cell count at 500 mg/kg and 1000 mg/kg would indicate a slight occurrence of allergy.

5 Conclusions

The phytochemical study of the hydro-ethanolic extract of Hydrocotyle bonariensis leaves revealed the presence of the main groups of bioactive chemical compounds such as alkaloids, tannins, flavonoids and saponosides. Cellular toxicity studies applied on shrimp larvae showed that this extract does not show cytotoxicity. The oral administration of the same extract showed neither acute nor subchronic toxicity in wistar rats at the studied doses. However, a chronic toxicity study of this hydroethanol extract should be considered in perspective as well as the toxicity study of the aqueous extract of the leaves and rhizomes of the same plant by considering many more toxicity indicator parameters. Histological studies would also be welcome to complete the toxicological evaluation of this plant.

Availability of data and materials

The datasets used and/or analyzed during this study are available from the corresponding author upon reasonable request.



Organisation for Economic Co-operation and Development


Serum glutamic-oxaloacetic transaminase


Serum glutamic pyruvic transaminase


Alkaline phosphatase level


White blood cells


  1. Ajani EO, Salako AA, Sharlie PD, Akinleye WA, Adeoye AO, Salau BA, Adebawo OO (2009) Chemopreventive and remediation effect of Hydrocotyl bonariensis Comm. Ex Lam (Apiaceae) leave extract in galactose induced cataract. J Ethnopharmacol 123(1):134–142

    Article  CAS  Google Scholar 

  2. Ajani EO, Salau BA, Adebayo OG, Oyefuga OH, Adebawo OO (2008) Evaluation of toxicological implications of administration of Hydrocotyl boanriensis leave extract in rats. In: Book of Abstract. 23rd Annual Session Nigerian Society of Biochemistry and Molecular Biology, p 43.

  3. Al-Habori M, Al-Aghbari A, Al-Mamary M, Baker M (2002) Toxicological evaluation of Catha edulis leaves: a long term feeding experiment in animals. J Ethnopharmacol 83:209–217

    Article  Google Scholar 

  4. Badiaga M (2011) Etude ethnobotanique, phytochimique et activités biologiques de Nauclea latifolia Smith, une plante médicinale africaine récoltée au Mali. Université de Bamako, p 136 +Annexes

  5. Burkill HM (1985) The useful plants of west tropical Africa, vol 5

  6. Dehou R, Dougnon V, Atchade P, Attakpa C, Legba B, Baba-Moussa L, Gbaguidi F (2018) Etude phytochimique et toxicologique de cassia italica, momordica balsamina et ocimum gratissimum, trois plantes utilisees contre la gale au sud-Bénin. Rev Ivoir Sci Technol 32:286–297

    Google Scholar 

  7. Dibong SD, Ottou PBM, Vandi D, Ndjib RC, Monkam Tchamaha F, Mpondo ME (2015) Ethnobotanique des plantes médicinales anti hémorroïdaires des marchés et villages du Centre et du Littoral Cameroun. J Appl Biosci 96:9072–9093

    Article  Google Scholar 

  8. Djengue HW, Dansi A, Assogba MF, Ahissou H, Adjatin A, Dansi M, Gbénou DJ (2017) Phytochemical screening and toxicity of Lippia multiflora Moldenke, a minor aromatic leafy vegetable consumed in Benin. Int J Curr Res Biosci Plant Biol 4(5):77–84

    Article  CAS  Google Scholar 

  9. Dufour DR, Lott JA, Nolte FS, Gretch DR, Koff RS, Seeff LB (2000) Diagnosis and monitoring of hepatic injury II. Recommandation for use of laboratory tests in screening, diagnosis and monitoring. Clin Chem 46:2050–2068

    Article  CAS  Google Scholar 

  10. Edeoga HO, Okwu OE, Mbaebie BO (2005) Phytochemical constituents of some Nigerian medicinal plants. Afr J Biotechnol 4:685–688

    Article  CAS  Google Scholar 

  11. Evans JP (1992) The effect of local resource availability and clonal integration on ramet functional morphology in Hydrocotyle bonariensis. Oecologia 89:265–276

    Article  Google Scholar 

  12. Gbenou JD, Ahounou JF, Ladouni P, Agbodjogbe WKDD, Tossou R, Dansou P (2011) Propriétés Anti-Inflammatoires Des Extraits Aqueux De Sterculia setigera Delile Et Du Mélange Aframomum melegueta K Schum-Citrus aurantifolia Christm Et Panzer. Int J Biol Chem Sci 5(2):634–641

    Google Scholar 

  13. Goodarzi MT, Zal F, Malakooti M, Safari MR, Sadeghian S (2006) Inhibitory activity of flavonoids on the lens aldose reductase of healthy and diabetic rats. Acta Med Iran 44:34–45

    Google Scholar 

  14. Gowda S, Desai PB, Kulkarni SS, Hull VV, Math AAK, Vernekar SN (2010) Markers of renal function tests. Am J Med Sci 2(4):170–173

    Google Scholar 

  15. Gregg LV, Voigt DVM (2000) Hematology techniques and concepts for veterinary technicians. Iowa State University Press, Iowa, pp 95–101

    Google Scholar 

  16. Hodgson E (2004) A textbook of modern toxicology, 3rd edn. Wiley Interscience, Hoboken, pp 525–541

    Book  Google Scholar 

  17. Houghton PJ, Raman A (1998) Laboratory handbook for the fractionation of natural extracts, 1st edn. Chapman and Hall, London, p 244

    Book  Google Scholar 

  18. Houmènou V, Adjatin A, Assogba F, Gbénou J, Akoègninou A (2018) Etude Phytochimique Et De Cytotoxicité De Quelques Plantes Utilisées Dans Le Traitement De La Stérilité Féminine Au Sud-Bénin. Eur Sci J 14(6):1857–7881

    Google Scholar 

  19. Bruneton J (1999) Pharmacognosie. Phytochimie. Plantes médicinales, 4e édition. TEC & DOC, Paris

  20. Klaassen CD, Casarett LJ, Doull J (2001) Casarett and Doull’s toxicology: the basic science of poisons. McGraw-Hill Press, New York

    Google Scholar 

  21. Koné M, Bleyere NM, Yapo AP, Vangah MO, Ehilé EE (2009) Evaluation de la toxicité d’un extrait aqueux de Sacoglottis gabonensis (Baille) Urban (Humiriaceae) chez les rongeurs, une plante utilisée dans le traitement de l’ulcère de Buruli en Côte d’Ivoire. Int J Biol Chem Sci 3(6):1286–1296

    Google Scholar 

  22. Lullmann-Rauch R (2008) Histologie. de Boeck Supérieur, Bruxelles

    Google Scholar 

  23. Macheix JJ, Fleuriet A, Jay-Allemand C (2005) Les composés phénoliques des végétaux : un exemple de métabolites secondaires d’importance écoomique. Presses Polytechniques et Universitaires Romandes (PPUR), Lausanne

    Google Scholar 

  24. Masoumian M, Arbakariya A, Syahida A, Maziah M (2011) Effect of precursors on flavonoid production by Hydrocotyle bonariensis callus tissues. Afr J Biotechnol 10(32):6021–6029

    CAS  Google Scholar 

  25. Monyn ED, Bakayoko A, Bi FHT, Yao K, Kone MW (2016) Niveau de connaissance et composition minérale de Hydrocotyle bonariensis Lam. (Araliaceae), une plante utilisée dans les ménages du District d’Abidjan (Côte d’Ivoire). Int J Biol Chem Sci 10(5):2046–2061

    Article  CAS  Google Scholar 

  26. Mousseux M (1995) Test de toxicité sur larves d’Artemia salina : entretien d’un élevage de balanes. Centre Universitaire de Nouvelle Calédonie, Nouméa

    Google Scholar 

  27. Michael AS, Thompson CG, Abramovitz M (1956) Artemiasalina as a test organism for a bioassay. Science 123:467505

    Article  Google Scholar 

  28. Migliore L, Civitareale C, Brambilla GDI, Delupis GD (1997) La toxicité des plusieurs aspects importants des antibiotiques agricoles face aux larvesde Artemia. Water Res 31:1801–1806

    Article  CAS  Google Scholar 

  29. Mira L, Fernadez MT, Santos M, Rocha R (2002) Interaction of flavonoids withy iron and copper ions: a mechanism for their antioxidant activity. Free Radic Res 36:1199–1208

    Article  CAS  Google Scholar 

  30. Mukinda JT, Syce JA (2007) Acute and chronic toxicity of the aqueous extract of Artemisia afra in rodents. J Ethnopharmacol 112:138–144

    Article  CAS  Google Scholar 

  31. Nga EN, Ngolsou F, Nyangono Ndongo M, Soppo Lobe V, Betoté DPH, Benga Mekoulou C, Maniepi N, Fifen R, Dimaïssou J, Eya'ane MF, Mpondo Mpondo E, Minkande Z (2020) Étude Toxicologique In Vivo de l'Extrait Aqueux des Feuilles de Psychotria Calceata. SCIENCES DE LA SANTÉ ET MALADIES 21(10)

  32. Obaseki OE, Adesegun OI, Anyasor GN, Abebawo OO (2016) Evaluation of the anti-inflammatory properties of the hexane extract of Hydrocotyle bonariensis Comm. Ex Lam leaves. Afr J Biotechnol 15(49):2759–2771

    Article  CAS  Google Scholar 

  33. Okwu DE (2007) NMAP. Sci Biotechnol 1(1):90–96

    Google Scholar 

  34. Palani S, Raja R, Kumar P, Jayakumar S (2009) Therapeutic efficacy of Pimpinella tirupatiensis (Apiaceae) on acetaminophen induced nephrotoxicity and oxidative stress in male albino rats. Int J PharmTech Res 1:925–934

    Google Scholar 

  35. Park HH, Lee S, Son HY, Park SB, Kim MS, Choi EJ, Singh TS, Ha JH, Lee MG, Kim JE, Hyun MC, Kwon TK, Kim YH, Kim SH (2008) Flavonoids inhibit histamine release and expression of proinflammatory cytokines in mast cells. Arch Pharm Res 31(10):1303–1311

    Article  CAS  Google Scholar 

  36. Houngbeme AG, Gandonou C, Yehouenou B, Kpoviessi SD, Sohounhloue D, Moudachirou M (2014) Gbaguidi FA (2014) Phytochemical analysis, toxicity and antibacterial activity of Benin medicinal plants extracts used in the treatment of sexually transmitted infections associated with HIV/AIDS. Int J Pharm Sci Res 5(5):1739–1745

    Google Scholar 

  37. Pratt DS, Kaplan MM (2000) Evaluation of abnormal liver-enzyme results in asymptomatic patients. N Engl J Med 342:1266–1271

    Article  CAS  Google Scholar 

  38. Tabopda TK, Mitaine-Offer AC, Miyamoto T, Tanaka C, Mirjolet JF, Duchamp O, Ngadjui BT, Lacaille-Dubois MA (2012) Triterpenoid saponins from Hydrocotyle bonariensis Lam. Phytochemistry 73(1):142–147.

    Article  CAS  PubMed  Google Scholar 

  39. Theo S, Stirling D, Thomas S, Hoberman A, Kiorpes A, Khetani V (2002) A 90-day oral gavage toxicity study of D-methylphenidate and D, L-methylphenidate in sprague-Dawly rats. Toxicology 179:183–196

    Article  Google Scholar 

  40. WHO (2015) Cardiovascular diseases (CVDs). Accessed March 7, 2021, at the following address

  41. Yessoufou A, Gbenou J, Grissa O, Hichami A, Simonin A-M, Tabka Z, Moudachirou M, Moutairou K, Khan NA (2013) Anti-hyperglycemic effects of three medicinal plants in diabetic pregnancy: modulation of T cell proliferation. BMC Complement Altern Med 13(77):13

    Google Scholar 

Download references


We would like to thank A. DIALLO and K. Atsu for their expertise. We thank the Pierre Fabre Foundation and Campus France for their technical support.



Author information

Authors and Affiliations



KK, AM, PB and TP conceived the project and defined research methodology; KK, KMD-Y, MA and B. K performed the experiments; KK, TP, PB and AM wrote the paper.

Corresponding author

Correspondence to Komla Kaboua.

Ethics declarations

Ethics approval and consent to participate

The research was conducted on laboratory rats in accordance with institutional guidelines of Laboratory of Physiology/Pharmacology of University of Lomé (ref:001/2012/CB-FDS-UL.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kaboua, K., Pakoussi, T., Mouzou, A. et al. Toxicological evaluation of Hydrocotyle bonariensis Comm. ex Lamm (Araliaceae) leaves extract. Beni-Suef Univ J Basic Appl Sci 10, 69 (2021).

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: