The hepatoprotective activity of water extract of the seed was evaluated in-vivo against carbon tetrachloride (CCl
4)(2 ml/kg
i.p) induced toxicity in rats [
35]. It was documented that the concentration of important liver toxicity biomarkers such as alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, total protein was increased in CCl
4 induced untreated animals. However, 28 days of oral exposure of the rats to 500 mg/kg of the extract significantly reduced the values of alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), total protein to 678 U/L, 42.40 U/L, 25.70 U/L and 6.88 (g/dl) respectively. The result suggests that the extract prevented haloakylation and lipid peroxidation of the liver tissue [
35]. Short term toxicity study in rabbits depicts that, the seed alcohol and water extracts did not elicit liver toxicity [
39]. This was inferred from the insignificant changes in the values of liver function markers viz. ALP, AST, ALT, total bilirubin, and conjugated bilirubin of the extract-treated animals [
39]. The result of the tissue histology showed no observable distortion in the architectural integrity of the liver vis-à-vis the control group [
41]. In another 21 days study, Ajiboye et al. [
39] established that a near-normal liver histo-architecture was found in high fructose-induced metabolic syndrome rats, treated with aqueous seed extract (400 mg/kg). A full lustre appearance, sparkling eyes, and normal fecal droppings are the few physical parameters that corroborated the biochemical and physiological wellness of the extract fed animals [
75]. Morphometric analysis and histology revealed that the aqueous seed and leaves extract (250 mg/kg) reversed streptozotocin-induced uneven distribution, distortion, vacuolation of pancreatic islet cell in rats [
29]. Congruently, 14 days of oral pretreatment with 25 and 50 mg/kg alkaloid fraction of
H. umbellate markedly improved the histological lesions of fatty hepatic degeneration induced by triton WR-1339 (200 mg/kg
i.p) [
71]. The possibility of the fruit pulp to elicit sub-acute toxicity was evaluated by Igbe et al. [
37]. The aqueous extracts (200, 400, and 800 mg/kg) was administered for 28 days in both sexes of animals. The effect of the extract on all doses on biochemical and serum electrolytes indices vis-à-vis the control was insignificant. At the highest dose of 800 mg/kg, parameters such as creatinine, urea, bicarbonate, total protein, ALP, AST, total albumin, ALT, glucose, conjugated bilirubin in the female and male animals measured (0.29 and 0.31 mg/dl), (27.10 and 27.00 mg/dl), (26.20 and 24.20 mMol/L), (6.60 and 5.60 mg/dl), (18.40 and 17.80 mg/dl), (134 and 135 IU/L), (0.22 and 0.20 mg/dl), (45.50 and 48.30 IU/L), (102.12 and 100.44 mg/dl) (0.12 and 0.11 mg/dl) respectively [
72]. Further histological assessment of the kidney, liver, and lungs revealed a protective effect of 800 mg/kg extract on the tissues. The data from the study concluded that sub-acute administration of aqueous fruit pulp extract is nontoxic, and no observable changes in the values of hematological parameters such as hemoglobin, hematocrit, red blood cells, white blood cells, platelets, mean platelet volume, granulocytes count, monocytes/eosinophil, lymphocytes, mean corpuscular volume, mean corpuscular hemoglobin concentration, red cell distribution width was detected [
37]. Nonetheless, Edosuyi et al. [
33] observed an increased platelet aggregation, suggesting that prolonged usage of the aqueous stem bark extract might be a risk factor for thrombotic complications. In 28 days sub-acute toxicity study, the aqueous stem bark extract (150, 300, and 600 mg/kg) was observed to be toxic [
33]. Histological examination revealed changes such as irregular glomeruli in the kidneys and the architectural configuration were not observed in control but seen in the heart, liver at 300 and 600 mg/kg water extract-treated animals. Alveolar hemorrhage and edema mild vascular congestion observed in the lungs and spleen respectively were not present in the control animals. A significantly increased creatinine value in 300 and 600 mg/kg extract exposed rat which was significantly greater than control animals is suggestive of damaged functioning nephrons [
33]. Increased mean corpuscular hemoglobin, reduced lymphocyte and red blood cells observed in the study are characteristic of macrocytic anemia. The extract significantly increased the activity of aspartate aminotransferase at 300 and 600 mg/kg which corroborated the mild liver inflammation observed in the histopathology diagnosis [
33]. Contrastingly, a 24-h acute toxicity study by Igbe et al. [
28] established that no adverse effect on hematological parameters such as white blood cell count and hematocrit values or mortality was detected in all aqueous seed extract (10, 12.5, 15 and 17.5 g/kg) treated group. As reported by Longe et al. [
30], extensive treatment of alloxan-induced diabetic rats with methanol seed extract (100 and 250 mg/kg), revealed that the extract at 100 mg/kg conferred a more potent hepatic protection in the diabetic rats. Comparatively, elevated values of AST, ALT, ALP, and total bilirubin were abrogated in the untreated animals from 15.60 U/L, 14.10 U/L, 92.10 U/L, and 0.76 mg/dl to 10.10 U/L, 11.10 U/L, 78.10 U/L and 0.59 mg/dl in the treated rats [
30]. As demonstrated Edosuyi et al. [
67], 14 days acute toxicity examination of 1000, 2000, 4000, and 8000 mg/kg stem bark water extract showed zero mortality of the treated mice. Toxicity signs and allergic reactions such as convulsion, diarrhea, Curtis anserina, sedation, horripilation, increased urination, and tremors were not exhibited by any animals in the different dosage groups. Intraperitoneal administration of the aqueous seed extract was analyzed for acute toxicity using Weibull and Probit mathematical tests. The result suggests that the mean lethal dose of extract was 1660 mg/kg and 1614 mg/kg respectively for the two mathematical models [
76]. Dismayingly, a very high mortality rate of 80 and 100% was observed at 1.8 and 2.0 g/kg extract-treated animals. Probit scores of 3.04, 5.25, 5.84, and 6.90 were recorded at 1.4 g/kg, 1.6 g/kg, 1.8 g/kg 2.0 g/kg extract dose respectively, indicating the slight toxicity of the extract considering the route of administration [
76]. On the other hand, an acute oral toxicity study in Swiss albino mice showed no mortality after 24 h of exposure to aqueous seed extract (1, 5, 10, and 15 g/kg), and no signs of delayed toxicity were exhibited 2 weeks post-treatment [
37].