Comparative Hepatoprotective Effects of Carica papaya, Azadirachta indica, and Allium sativum Extracts against Diethyl Nitrosamine-Induced Liver Injury in Wistar Rats
Aug 2026· African Journal of Clinical Medicine and Pharmacy Research· 0 citations· 15 references
TL;DR
It is indicated that combining papaya, neem, and garlic extracts may provide greater hepatoprotection than administering the individual extracts against DEN-induced liver injury, and supports further mechanistic and preclinical evaluation of this polyherbal formulation before its potential therapeutic application in liver-disease management.
Abstract
Diethylnitrosamine (DEN) induces oxidative stress, lipid peroxidation, and hepatocellular damage, highlighting the need to identify effective hepatoprotective agents. Although Carica papaya, Azadirachta indica, and Allium sativum possess recognized antioxidant and anti-inflammatory potential, evidence regarding their combined hepatoprotective effects remains limited. This study compared the effects of their individual and combined extracts against DEN-induced liver injury in male albino Wistar rats. Rats weighing 150–200 g were allocated to six groups (n = 6): normal control, DEN-only, papaya extract, neem extract, garlic extract, and combined-extract groups. DEN was administered intraperitoneally at 100 mg/kg once weekly for eight weeks. Ethanolic plant extracts prepared through Soxhlet extraction were administered orally at doses ranging from 100 to 400 mg/kg daily. Serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, bilirubin, malondialdehyde, and glutathione concentrations were assessed using standard biochemical assays, while liver tissues were evaluated histologically following hematoxylin and eosin staining. Data were analyzed using analysis of variance followed by Tukey’s post hoc test, with statistical significance established at p < 0.05. DEN exposure significantly increased liver enzymes, bilirubin, and malondialdehyde while reducing glutathione, confirming substantial hepatic injury. The individual extracts provided moderate protection, as demonstrated by partial normalization of biochemical markers and improved histological features. Hepatoprotection increased with dosage, with the strongest effects observed at 300–400 mg/kg. The combined extract produced the greatest protective effect, with biochemical indices approaching normal control values, improved antioxidant status, and restoration of hepatic architecture. These findings indicate that combining papaya, neem, and garlic extracts may provide greater hepatoprotection than administering the individual extracts against DEN-induced liver injury. The study supports further mechanistic and preclinical evaluation of this polyherbal formulation before its potential therapeutic application in liver-disease management.
Background: Diabetes mellitus is accompanied by biochemical and structural disturbances that may extend to the liver and kidneys. Vernonia amygdalina (bitter leaf) and Ocimum gratissimum (scent leaf) are widely used African medicinal plants with reported antioxidant and metabolic activities. Objective: This article evaluated the hepatorenal effects of ethanolic leaf extracts of V. amygdalina and O. gratissimum, administered individually and in combination, in streptozotocin (STZ)-induced diabetic Wistar rats. Methods: The study used 72 Wistar rats. Diabetes was induced with 65 mg/kg STZ following two weeks of high-fat feeding. Animals were assigned to normal control, diabetic untreated, metformin-treated, V. amygdalina-treated, O. gratissimum-treated, and combined-extract groups. Ethanolic extracts were prepared by Soxhlet extraction and administered orally for 28 days. Hepatic indices included alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin and total protein; renal indices included urea, creatinine, potassium, sodium and bicarbonate. Results: Relative to the untreated diabetic group, individual extracts produced generally lower hepatic and renal biochemical indices, with O. gratissimum showing the more favourable numerical pattern. ALP, ALT, AST and total bilirubin were 66.50 ± 1.40 U/L, 18.97 ± 0.23 U/L, 70.00 ± 0.91 U/L and 0.21 ± 0.01 mg/dL, respectively, in the O. gratissimum group, compared with 83.50 ± 1.27 U/L, 28.77 ± 0.20 U/L, 81.70 ± 1.30 U/L and 0.28 ± 0.01 mg/dL in untreated diabetic rats. Similarly, creatinine decreased from 0.41 ± 0.02 mg/dL in the diabetic control to 0.33 ± 0.01 mg/dL with O. gratissimum. In contrast, the combined extract produced the highest ALP, ALT, AST, bilirubin, urea, creatinine and electrolyte values and was accompanied by hepatic and renal structural abnormalities. Conclusion: Under the experimental conditions, the individual ethanolic extracts, particularly O. gratissimum, were associated with improved hepatorenal biochemical indices, whereas combined administration was associated with marked hepatic.
C. G. Ehie, Ahamefula Sunday Ezekwe, A. Okari et al.· Health Science Research Inte...· 0 citations
Introduction: Paracetamol (PCM) overdose is a major contributor to acute liver failure, mainly resulting from oxidative stress and the depletion of Glutathione (GSH) triggered by its toxic byproduct, N-Acetyl-P-Benzoquinone Imine (NAPQI). Conventional hepatoprotective agents have limitations, prompting interest in medicinal plants. Tagetes patula (French marigold), traditionally used for hepatic disorders, contains flavonoids and terpenoids with potential antioxidant activity, but its hepatoprotective effects remain underexplored.
Aim: To evaluate the hepatoprotective effect of Aqueous Extract of Tagetes patula flowers (AETP) against PCM-induced hepatotoxicity in rats.
Materials and Methods: This an experimental animal study was conducted at the Departments of Pharmacology and Pathology, Regional Institute of Medical Sciences (RIMS), Imphal, India from November 2021 to May 2022. A total of 25 adult male Wistar albino rats were divided into five groups (n=5). Group I received vehicle (control), Group II received PCM (2 g/kg; toxic control), Group III received PCM + silymarin (25 mg/kg; standard), and Groups IV and V received PCM + AETP (200 mg/kg and 400 mg/kg, respectively) for seven days. Serum AST, ALT, and ALP levels were measured, and liver histology was examined. Data were analysed using one-way Analysis of variance (ANOVA) with Bonferroni post-hoc test.
Results: The PCM caused significant elevation of AST, ALT, and ALP (p<0.001) and severe histopathological damage. Silymarin markedly reduced enzyme levels and preserved hepatic architecture. AETP treatment produced a dosedependent hepatoprotective effect: 200 mg/kg partially improved biochemical and histological parameters, while 400 mg/kg significantly reduced enzyme levels (p<0.05 vs toxic) and showed improved hepatic architecture.
Conclusion: The AETP flower extract demonstrates dosedependent protective effects on the liver against PCM-induced liver injury, likely attributed to its antioxidant and anti-inflammatory phytochemicals. Additional research is required to elucidate its underlying mechanisms and validate its therapeutic efficacy
Abhishek Bhattacharjee, P. Paul, Sumana Majumder et al.· Journal of Clinical and Diag...· 0 citations
Aims: To evaluate the protective effects of hydromethanolic leaf extracts of Carica papaya and Chromolaena odorata, administered individually and in combination, against cadmium-induced intestinal oxidative damage in Wistar rats.
Study Design: Experimental animal study.
Place and Duration of Study: Animal House, Department of Animal and Environmental Biology, Rivers State University, Port Harcourt, Nigeria, between February 2025 and October 2025.
Methodology: Forty-eight albino Wistar rats were randomly assigned to eight groups (n = 6). Intestinal injury was induced by oral administration of cadmium chloride (20 mg/kg body weight) for 14 days, followed by treatment with hydromethanolic leaf extracts of Carica papaya (300 and 600 mg/kg), Chromolaena odorata (250 and 500 mg/kg), or their combined extracts (300 and 600 mg/kg) for 14 days. Phytochemical constituents of both plants were identified using gas chromatography–mass spectrometry, while heavy metal contents were determined by atomic absorption spectrophotometry. Serum cadmium concentration, intestinal oxidative stress biomarkers (superoxide dismutase, catalase, glutathione peroxidase, and malondialdehyde), and histopathological changes were evaluated using standard analytical methods. Data were analysed using one-way analysis of variance followed by Tukey's post hoc test at P < 0.05.
Results: Gas chromatography–mass spectrometry revealed the presence of diverse bioactive phytochemicals in both plant extracts, while heavy metal concentrations were within recommended safety limits. Cadmium exposure significantly increased serum cadmium concentration and malondialdehyde levels while significantly reducing superoxide dismutase, catalase, and glutathione peroxidase activities compared with the normal control (P < 0.05). Treatment with the hydromethanolic leaf extracts significantly reduced serum cadmium concentration, restored antioxidant enzyme activities, decreased lipid peroxidation, and improved intestinal histoarchitecture in a dose-dependent manner. The high-dose C. papaya extract showed the greatest recovery of superoxide dismutase activity, whereas the high-dose combined extract was most effective in reducing lipid peroxidation and improving intestinal histoarchitecture.
Conclusion: Hydromethanolic leaf extracts of Carica papaya and Chromolaena odorata protected against cadmium-induced intestinal oxidative injury by reducing cadmium burden, improving antioxidant status, and preserving intestinal tissue architecture. While the high-dose C. papaya extract produced the greatest recovery of superoxide dismutase activity, the combined extract showed marked protective effects, particularly in reducing lipid peroxidation and preserving intestinal histoarchitecture, suggesting its potential as a phytotherapeutic approach against cadmium-induced intestinal toxicity.
Igattah, Prudence Akachukwu, Waribo, Helen Anthony, Ibama Onengiyeofori· European Journal of Medicina...· 0 citations
Drug-induced liver injury is a major health concern and represents one of the most common causes of acute liver failure. Diclofenac, a widely prescribed non-steroidal anti-inflammatory drug (NSAID), is known to induce hepatotoxicity through oxidative stress, mitochondrial dysfunction, and the formation of reactive metabolites. Natural products with antioxidant properties have gained attention as potential hepatoprotective agents. Impatiens balsamina Linn. is a medicinal plant traditionally used for various therapeutic purposes and is rich in flavonoids, phenolic compounds, tannins, and other bioactive constituents with potent antioxidant activity. The present study was undertaken to evaluate the hepatoprotective activity of the hydroalcoholic extract of Impatiens balsamina leaves (HAEIB) against diclofenac-induced hepatotoxicity in experimental rats. HAEIB treatment significantly restored altered biochemical parameters, increased GSH and SOD levels, and reduced LPO levels compared with the diclofenac-treated group, indicating attenuation of oxidative stress. Histopathological examination revealed marked protection against hepatic degeneration, necrosis, and inflammatory cell infiltration. HAEIB at a dose of 400 mg/kg demonstrated hepatoprotective activity comparable to that of the standard drug silymarin. These findings suggest that the hepatoprotective effect of HAEIB may be attributed to its antioxidant phytoconstituents and support its potential use as a natural hepatoprotective agent.
Shweta Patil, Aglawe Sachin, Pratiksha Vadhane et al.· Genetics and Molecular Resea...· 0 citations
Potassium bromate (KBr) is a potent oxidizing agent that induces oxidative stress, inflammation, and hepatic injury. This study evaluated the protective effects of Solanum aethiopicum leaf extract against KBr-induced alterations in liver function and inflammatory cytokines in Wistar rats. Thirty Wistar rats (140–150 g) were randomly assigned to five groups (n = 6): normal control, KBr (50 mg/kg), KBr + S. aethiopicum extract (300 mg/kg), KBr + S. aethiopicum extract (600 mg/kg), and KBr + vitamin C (100 mg/kg). Potassium bromate was administered for two weeks before treatment with the extract or vitamin C. Serum liver function indices (total protein, albumin, globulin, ALT, AST, ALP, and total bilirubin) and inflammatory biomarkers (IL-1β and TNF-α) were determined using standard spectrophotometric methods. Data were analyzed using one-way ANOVA followed by Tukey’s post hoc test. Potassium bromate significantly disrupted liver function parameters and reduced (P < 0.05) IL-1β levels compared with the control, indicating hepatic dysfunction and impaired inflammatory homeostasis. Treatment with S. aethiopicum extract significantly restored IL-1β concentrations while maintaining TNF-α levels comparable to the control. The extract also ameliorated KBr-induced alterations in serum proteins and bilirubin. In conclusion, S. aethiopicum leaf extract protected against potassium bromate-induced hepatic dysfunction and inflammatory disturbances, supporting its potential as a natural hepatoprotective and immunomodulatory agent. Further studies are recommended to elucidate its underlying mechanisms of action.
Keywords: inflammation, interleukin-1β, tumor necrosis factor-α, potassium bromate, Solanum aethiopicum.
Okon Victoria Edem, Idam Benedict Umagu, I. Nnah· IAA Journal of Biological Sc...· 0 citations