Antioxidant and hepatoprotective potentials of ethanol stem bark extract of Daniela oliveri (Rolfe) Hutch and Dalz (Caesalpinaceae)

Study of Silymarin on Ethanol Induced Hepatotoxicity and Expression of Bcl-2, Bax and p53 Levels

Hepatoprotective Action of Dehydrozingerone in Carbon Tetrachloride and Thioacetamide-induced Hepatotoxicity in Wistar Rats

Daniella oliveri is a deciduous plant that is commonly found in savanna and open grassland. Various parts of the plant is used by herbalist in the management of different ailments. The present study aims at investigating the hepatoprotective and antioxidant activity of the methanolic extract of D. oliveri leaves. The hepatoprotective activity was investigated using carbon tetrachloride (CCl4)-induced hepatotoxicity in albino rats. The antioxidant activity was determined using both in vitro (2, 2-diphenyl-1-picrylhydrazine photometric assay) and in vivo (malondialdehyde and catalase level assay) models. The pretreatment with extract (100, 200, and 400 mg/kg) and silymarin (100 mg/kg) produced a significant (p<0.05) dose-dependent increase in hepatoprotective activity when compared with the negative control group. The extract (25-400 μg/mL concentration) produced a concentration-dependent increase in antioxidant activity in 2, 2-diphenyl-1-picrylhydrazine (DPPH) photometric assay. The IC50 of the extract in DPPH photometric assay was 400 μg/mL concentrations. The extract and silymarin showed a significant (p<0.05) dose-dependent increase in catalase level in treated rats when compared with the negative control group. Also, the extract and silymarin produced a significant (p<0.05) dose-dependent decrease in malondialdehyde level in treated rats when compared with the negative control group. The results of the study suggest that D. oliveri leaves has a potent hepatoprotective activity that may be linked to its antioxidant activities and validates its use in the traditional management of liver disorders.

Ganoderic acid -loaded solid lipid nanoparticles ameliorate d-galactosamine induced hepatotoxicity in Wistar rats

Chemical/drug-induced hepatotoxicity has become one of the major concerns in medical practice. This study was designed to evaluate the possible protective effects of diphenyl diselenide (DS) against carbon tetrachloride (CCl4) and diethylnitrosamine (DEN)-induced hepatotoxicity in male Wistar rats. Forty male Wistar rats (100-120 g) were assigned into five groups of eight animals. Group 1 served as control, group 2 was given DEN (100 mg/kg) + CCl4 (0.5 ml/kg), group 3 received DEN (100 mg/kg) + CCl4 (0.5 ml/kg) + DS (5 mg/kg), group 4 received DEN (100 mg/kg)+CCl4 (0.5 ml/kg)+DS (10 mg/kg), and group 5 received DEN (100 mg/kg)+CCl4 (0.5 ml/kg)+Quercetin (QUE; 50 mg/kg). Administration of DEN and CCl4 increased the activities of serum alanine aminotransferase, myeloperoxidase, and total bilirubin level relative to controls. There were significant (p&lt;0.05) decreases in the activities of hepatic superoxide dismutase, glutathione-s-transferase, catalase and level of total sulfhydryl by 0.72±0.03 vs 4.55±0.28, 8.8±0.74 vs 10.94±2.67, 27.17±5.49 vs 59.75±7.87 and 0.46±0.02 vs 0.60±0.01, respectively, while hepatic malondialdehyde level increased by 4.71±0.52 vs 1.68±0.43 in the [DEN+CCl4]-administered group relative to controls. The levels of TNF-ɑ and IL-1β also increased, while the BAX/BCl2 ratio decreased in the [DEN+CCl4]-administered group. Importantly, administration of DS at 10 mg/kg increased the activities of antioxidant enzymes, and BAX/BCl2 ratio and decreased the levels of inflammatory markers. Taken together, diphenyl diselenide confers protection against DEN+CCl4-induced hepatic damage via anti-oxidative and anti-inflammatory activities.

Antioxidant and hepatoprotective activity of Fagonia schweinfurthii (Hadidi) Hadidi extract in carbon tetrachloride induced hepatotoxicity in HepG2 cell line and rats

Background: The global rise in liver diseases associated with environmental toxins and lifestyle factors has intensified interest in functional foods with hepatoprotective properties. Moringa oleifera, a multipurpose, edible plant with established nutritional value, represents a promising candidate as a functional food due to its bioactive compound profile and traditional medicinal applications. Objective: This investigation evaluated the antioxidant and hepatoprotective properties of methanol extract from Moringa oleifera leaves (MOEXT) against carbon tetrachloride (CCl₄)-induced liver damage in experimental rats, with a specific focus on its potential as a functional food ingredient for liver health. Methods: We assessed MOEXT's antioxidant capacity through DPPH scavenging, ABTS neutralization, and ferric reduction assays. Safety evaluation followed OECD protocol 423. Hepatoprotective evaluation utilized the CCl₄ liver damage model in Wistar rats, with assessment of liver biomarkers, oxidative stress indicators, and tissue morphology. Functional food applications were evaluated based on bioactive compound stability and efficacy. Results: MOEXT exhibited concentration-dependent antioxidant properties with IC₅₀ values of 28.4 ± 2.1 μg/mL (DPPH) and 31.7 ± 1.8 μg/mL (ABTS). Safety studies indicated LD₅₀ exceeding 5000 mg/kg, supporting its food safety profile. MOEXT significantly (p &lt; 0.001) prevented CCl₄-induced increases in liver enzymes (AST, ALT, ALP) and bilirubin concentrations. The extract enhanced antioxidant enzyme function (SOD, CAT, GPx) and decreased lipid peroxidation markers. Microscopic examination confirmed protective effects on liver structure, demonstrating the potential for incorporating M. oleifera into functional food products. Conclusion: MOEXT demonstrates significant antioxidant and hepatoprotective activities, supporting its development as a functional food ingredient for liver health maintenance. These findings provide scientific validation for incorporating M. oleifera into nutraceutical and functional food products targeting hepatic wellness. Keywords: Moringa oleifera, functional foods, nutraceuticals, liver protection, antioxidant activity, bioactive compounds, agricultural biotechnology

The pharmacological effects of medicinal plants are due to the presence of certain chemical compounds present in them. Previous studies have shown that crude extracts of Tapinanthus bangwensis ( T. bangwensis) possess hepatocurative potential. However, the present study aims on evaluating the antioxidant activity as well as identifying the chemical compounds in ethylacetate fraction of T. bangwensis that ameliorate carbon tetrachloride-induced hepatotoxicity in Wistar rats. Six subfractions of ethylacetate fraction were obtained by column chromatography. The antioxidant activity was determined by 2,2-diphenyl-1-picrylhydrazine (DPPH), biochemical assay determined by spectrophotometry, and compound elucidation by liquid chromatography–mass spectroscopy (LC-MS) analysis. The DPPH result shows that subfraction F0 exhibited the strongest antioxidant activity followed by F4 while F1 exhibited the lowest. Oral administration of 100 mg/kg body weight of the subfractions of ethylacetate fraction of T. bangwensis increases superoxide dismutase and catalase activities and also glutathione level and decreases malondialdehyde level compared to the positive control group. Subsequently, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total bilirubin, and conjugated bilirubin were reduced while albumin and total protein levels increased compared to the positive control group. However, there were no significant differences between the positive control group and the group induced and treated with the subfractions at p &lt; 0.05. The histopathology study shows normal hepatocyte distribution with no fat deposit in the induced and treated groups while fatty liver was observed in the positive group. The anti-hepatotoxic effect was higher in F4 than in other subfraction treated groups. Hence, the LC-MS analysis of F4 reveals the presence of 8-hydroxyluteolin-8-glucoside, Avicularin, Fisetin-7-glucoside, Isoscutellarein-7-xyloside, and Isovitexin, respectively, and has been reported to exhibit antioxidant and hepatocurative activities. It can be concluded that the hepatocurative effect could be due to the chemical compounds identified above.

Persicaria maculosa (linn.) contains antibacterial, anti-inflammatory, and antioxidant activities, although its protective effects in liver cells are debatable. The effect of Persicaria maculosa (PM) and its active principle, tannic acid (TA), aqueous extracts on carbon tetrachloride-induced hepatotoxicity in rats was investigated in this work. Forty-two male Wistar rats were divided into seven groups: group-I act as Normal group), group-II (Toxicant group CCl 1.5ml/kg i.p), group-III Standard group which pre-treated with silymarin (100mg/kg/day), groups-IV &amp; V which were pretreated with PM aqueous extracts at a dosage of 200 &amp; 400 mg/kg/day o.p, followed by CCl groups-VI &amp; VII which were pretreated with aqueous extracts of TA at doses of 200 &amp; 400 mg/kg/day o.p followed by CClrespectively. After 14 days, liver enzymes such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP), bilirubin (BIL), and also oxidative stress biomarkers including lipid peroxidation (LPO), in vitro antioxidant activity were measured by 2,2′- diphenyl-1-picrylhydrazyl DPMH. Quantitative determination of some vital phytochemicals, and the histopathological changes were determined using standard procedure. The findings showed that CCl caused a remarkable rise in levels of serum hepatic enzymes such as ALT, AST, ALP and BIL (P≤0.001) compared with the control group. In addition, CCl led to the increasing of LPO (P≤0.001) in liver tissue in comparison with the control group. Rats pretreated with silymarin significantly reduced the adverse effects of CCl on serum and tissue markers. In this regard, remarkable vascular congestion, hepatocellular degeneration, and vacuolization were observed in hepatic tissue of CCl-treated rats. The pre-treatment of Persicaria maculosa and tannic acid aqueous extracts shows a significant improvement was observed in the functional and oxidative stress indices of hepatic tissue alongside histopathology changes.The current investigation found that Persicaria maculosa and its active ingredient Tannic acid aqueous extracts may help to reduce hepatic oxidative injury in rats exposed to CCl by enhancing the oxidant/antioxidant balance.

Phyllanthus acidus (L.) Skeels fruit is used as a liver tonic in Indian traditional medicine. The present study was undertaken to investigate the protective effects of ethanolic extract (70%) of Phyllanthus acidus fruits (PAE) on acetaminophen (paracetamol, APAP) induced acute hepatotoxicity in Wistar rats. The effect on cytochrome P450 enzyme system using pentobarbital induced sleeping time (PST) and free radical scavenging potential using 2,2-diphenyl-1-picrylhydrazil (DPPH) was also determined. Hepatotoxicity was achieved by administering a single oral dose of APAP (2 g/kg). PAE administered at a dose of 125, 250 and 500 mg/kg, p.o. showed a significant hepatoprotection against APAP-liver toxicity as evidenced by reduced serum markers and histopathological observation of liver tissues. Reduced enzymatic and nonenzymatic antioxidant levels and elevated lipid peroxidation due to APAP intoxication, were significantly restored to normalcy by pretreatment with PAE. The PAE also showed prolongation of PST and DPPH scavenging potential. The results were compared with silymarin (100 mg/kg, p.o.), which found more effective than plant extract being tested. Collectively, the preset study clear that the ethanolic extract of Phyllanthus acidus fruit has hepatoprotective activity against APAP-induced hepatotoxicity in rats and this is likely mediated through the inhibition of P450-mediated APAP bioactivation, free radical scavenging and antioxidant activities.

Reports about the impact of Carbon tetrachloride (CCl4) hepatotoxicity on coagulation profile have been inconsistent. Multiple investigators have however demonstrated the effectiveness of silymarin in the resolution of anomalies induced by CCl4, although the effect of silymarin on the impact of CCl4 hepatotoxicity, especially coagulation profile and osmotic fragility have not been investigated. The liver, the primary site for the secretion of coagulation proteins, can become impaired in CCl4 hepatotoxicity, and silymarin reportedly increases hepatic protein synthesis as part of its hepatoprotective mechanism. This study assessed the effect of silymarin on blood coagulation profile and erythrocyte osmotic fragility in CCl4 induced hepatotoxicity in rats. Twenty male Wistar rats were allocated into four groups (n = 5) at random, namely: Control, CCl4 given CCl4 (1 ml/kg) administered intraperitoneally twice a week, Silymarin (S) given silymarin (100 mg/kg/day) orally, and S+CCl4 given silymarin (100 mg/kg/day) orally and (1 ml/kg) CCl4 one hour after, intraperitoneally twice a week for a duration of four weeks. Results showed protraction of activated partial thromboplastin time and thrombin time, increased erythrocyte osmotic fragility, liver damage, dyslipidemia, oxidative stress and lipid peroxidation in rats given CCl4. Silymarin attenuated most of these effects as observed from comparison between CCl4 and S+CCl4 rats. The findings of this study suggests that pretreatment with silymarin attenuated disruption in coagulation profile and erythrocyte osmotic fragility in CCl4 induced hepatotoxicity in Wistar rats.

Background: The liver is highly susceptible to drug- and chemical-induced injury. Isoniazid and thioacetamide are known hepatotoxins that cause oxidative damage. R. communis leaves possess bioactive compounds with reported antioxidant and hepatoprotective potential. This study evaluated the hydroalcoholic leaf extract of R. communis against isoniazid and thioacetamide induced hepatotoxicity in Wistar rats. Methods: Wistar rats were divided into five groups in each model. Each group consisted of five animals. Hepatotoxicity was induced using isoniazid (250 mg/kg, p.o., 14 days) and in another model using thioacetamide (400 mg/kg, i.p., 3 days). Test groups received R. communis extract at 250 and 500 mg/kg, with Liv.52 (400 mg/kg) as standard. Serum hepatic markers, body weight, liver-to-body weight ratio, and liver histology were assessed. Antioxidant activity was determined by ferric reducing antioxidant power assay. Data were analyzed using one-way ANOVA followed by Tukey’s test. Results: In the isoniazid model, RIC 250 mg/kg and 500 mg/kg significantly reduced ALT levels (p&lt;0.05), however at 500 mg/kg, the extract increased AST and ALP levels. The liver-to-body weight ratio decreased significantly in treatment groups. Histology revealed minimal hepatic changes compared to moderate-to-severe injury in controls. In the thioacetamide model, R. communis produced mild biochemical improvement but caused mortalities in both dose groups. FRAP assay confirmed antioxidant potential (EC₅₀=12.39 µg/ml). Conclusions: R. communis extract demonstrated significant hepatoprotective and antioxidant activity, particularly at 250 mg/kg. However, the inconsistent effects at a higher dose and observed mortalities in the TAA model necessitate further investigation into its safety and therapeutic window.

Hepatoprotective drugs are not available for use in modern medicine and different parts of medicinal plants like Neem (Azadirachta indica) are used as hepatoprotectants in traditional medicine. Although there are scientific reports of its hepatoprotective activity on acute administration, we found only one study which had evaluated its hepatoprotective effect on chronic administration. Objectives: To evaluate the effect of chronic oral administration of Neem on paracetamol-induced hepatotoxicity in Wistar rats. Methods: We randomly assigned 72 male and female Wistar albino rats to four groups of 18 animals each and orally administered Distilled water 5ml/kg body weight/day to Groups A (Normal control) and B (Experimental control), 500 mg/kg aqueous Neem leaf extract (Test) to Group C and Silymarin suspension (Standard) 100mg/kg/day to Group D for 30 days. On the 8th day, we induced hepatotoxicity with Paracetamol 2g/kg body weight single dose to groups B, C and D. We performed liver function tests, recorded liver weights and examined liver histology of six rats from each group on 10th, 20th and 30th days. Results: We observed significant difference (P

Hepatoprotective and proteomic mechanism of Sphaeranthus indicus in paracetamol induced hepatotoxicity in wistar rats

Introduction: The aim of the study was to evaluate the hepatoprotective effect of aqueous extract of Garcinia kola) seeds on carbon tetrachloride (CCl4) induced liver damage in adult Wistar rats. Thirty adult Wistar rats weighing between 65-145g were randomly divided into six groups of 5 rats each. Group A (control) rats were orally administered with 5ml/kg body weight of distilled water daily for 2 weeks, group B rats were administered distilled water orally daily for 2 weeks (volume per body weight) and carbon tetrachloride (CCl4) 0.4 m1/kg intraperitonially as a single application on day 14 of the experiment. Group C rats were administered 100 mg of silymarin / kg body weight once daily for 2 weeks followed by a single dose of CCl4 (0.4 m1) on day 14 of the experiment. Group D rats were administered 400 mg aqueous extract bitter kola (Garcinia kola) / kg body weight orally once daily for 2 weeks. Group E and F rats were administered 400 mg and 200 mg aqueous extract bitter kola (Garcinia kola) seed) orally once daily for 2 weeks followed by a single dose of CCl4 (0.4 m1) on day 14 respectively. At the end of the experiment. Garcinia kola seed aqueous extract caused significant decrease in the aspartate aminotransferase (AST) levels in the serum of the extract treated groups. Histopathological examinations revealed distortion of histoarchitecture such as, sinusoidal congestion, necrosis, steatosis and fibrosis was observed in group B. The administration of aqueous extract of Garcinia kola seed remarkably inhibited histoarchitectural distortion induced by CCl4 administration. Effects of the extract at dose of 200mg/kg was comparable to the reference drug. Garcinia kola aqueous seed extract showed a remarkable hepatoprotective and antioxidant activity against CCl4 induced hepatotoxicity as observed from the serum marker enzymes and antioxidant levels in liver tissues. CCl4 induced a significant rise in AST, ALT, and ALP with an increase of superoxide dismutase (SOD), catalase (CAT) and reduction lipid peroxidation (MDA). Treatment of the rats with the extract significantly (p&lt;0.05) altered serum marker enzymes and antioxidant levels to near normal compared with CCl4- treated rats (group B). The activity of the extract at dose of 400mg/kg (group F) was comparable to the standard drug confirmed by histopathological examinations of liver sections. Conclusion: Garcinia kola aqueous extract has hepatoprotective and antioxidant properties against CCl4-induced hepatotoxicity in Wistar rats.