Effect of standardized Eucalyptus globulus leaf extract on brain oxidative stress and aberrant neurochemistry of fructose-streptozotocin-induced diabetic rats.

The neuro-pharmacological effect of Eucalyptus globulus ethanol leaf extract in fructose-streptozotocin-induced diabetic rats was evaluated in this study. The phytochemical analysis of the extract was carried out using HPLC-DAD. Diabetes was induced in rats with 10% fructose in drinking water and a single intraperitoneal injection of 40 mg/kg streptozotocin (STZ). Diabetic animals were orally treated with 100-400 mg/kg of the extract for 21 days with glibenclamide as the reference drug. Blood and brain tissue were processed for the determination of serum electrolyte levels, hematological indices, and biochemical estimations. Ergosterol, pinitol, catechin, quercetin, robinetinidol, and other polyphenols were identified in the extract. Diabetic animals showed decreased serum potassium and sodium ion levels and decreased hematocrit, hemoglobin, red blood cells, white blood cells and lymphocytes but increased neutrophils. The brains of animals in the untreated diabetic group with increased blood glucose level showed oxidative stress (increased level of MDA and myeloperoxidase but decreased level of reduced glutathione and superoxide dismutase) and disturbed neurochemistry (increased level of acetylcholinesterase and monoamine oxidase but decreased level of Na+K+ATPase, tyrosine hydroxylase and dopamine). Administration of the Eucalyptus globulus leaf extract remarkably ameliorated the observed hyperglycemia, electrolyte, and hematological imbalances in animals. In addition, the administration of the extract attenuated the brain redox imbalance, and neurochemical disturbances in the rats. These results show that Eucalyptus globulus leaves contain antioxidant and neurotransmitter modulating phytochemicals with the potential to be developed as therapeutic agents for the management of diabetic cerebrovascular problems and related complications.

Neuroprotective flavonoids of the leaf of Antiaris africana Englea against cyanide toxicity.

ETHNOPHARMACOLOGICAL RELEVANCE: Different parts of Antiaris africana Englea (Moraceae) are used traditionally for the treatment of various diseases, including epilepsy and other nervous system disorders. AIMS OF THIS STUDY: The current study was designed to evaluate the neuroprotective activity of flavonoids isolated from A. africana against potassium cyanide (KCN)-induced oxidative damage in brain homogenate. MATERIALS AND METHODS: Dried and ground leaves of A. africana were extracted with methanol and fractioned into n-hexane (HFA), dichloromethane (DFA), ethyl acetate (EFA) and methanol (MFA). Each fraction was assessed for neuroprotective potential by anticholinesterase activity test. The fraction with the best anticholinesterase activity was subjected to various chromatographic techniques through bioassay-guided fractionation to isolate the bioactive compounds. The protective ability of the extract, fractions and compounds against Potassium cyanide (KCN)-induced mitochondrial damage in rat brain homogenate was evaluated. Structures of the isolated compounds were determined using 1D and 2D NMR, mass spectrometry and by comparison with literature data. RESULTS AND DISCUSSION: The ethyl acetate fraction showed the best anticholinesterase activity with an IC50 of 23.23 ± 1.12 µg/ml. Quercetin and a biflavonoid glucoside identified as 3'-4'-bisquercetin-3ß-D-diglucoside from this fraction displayed a remarkable antioxidant activity in the DPPH assay and showed significant (P < 0.05) increase in the activity of dehydrogenase inhibited by KCN in a concentration dependent manner. However, quercetin was more effective in reducing the MDA level and acetylcholinesterase activity that were elevated by KCN. CONCLUSION: Quercetin and the bisquercetin-diglucoside isolated from the leaves of A. Africana for the first time, are major contributors to the observed neuroprotective property of the plant which supports its folkloric usage in the management of seizures, epilepsy and other neurological disorders.

Reduction of anoxia-induced bioenergetic disturbance in astrocytes by methanol fruit extract of Tetrapleura tetraptera and in silico evaluation of the effect of its antioxidative constituents on excitotoxicity.

Oxidative stress and excitotoxicity are some of the pathophysiological abnormalities in hypoxia-induced brain injury. This study evaluated the intrinsic antioxidant property of methanol fruit extract of Tetrapleura tetraptera (TT), traditionally used for managing brain diseases such as cerebral infarction in West Africa, and its ability to protect primary astrocytes from anoxia-induced cell death. The effect of the phytochemicals present in TT on excitotoxicity was assessed in silico, through docking with human glutamate synthetase (hGS). Chromatographic and spectrophotometric analyses of TT were performed. Primary astrocytes derived from neural stem cells were treated with TT and its effect on astrocyte viability was assessed. TT-treated astrocytes were then subjected to anoxic insult and, cell viability and mitochondrial membrane potential were evaluated. Molecular docking of hGS with detected phytochemicals in TT (aridanin, naringenin, ferulic acid, and scopoletin) was performed and the number of interactions with the lead compounds, aridanin, analyzed. HPLC-DAD analysis of TT revealed the presence of various bioactive phytochemicals. TT demonstrated notable antioxidant and radical scavenging activities. TT also protected astrocytes from anoxic insult by restoring cell viability and preventing alteration to mitochondrial membrane integrity. Aridanin, naringenin, ferulic acid, and scopoletin demonstrated good binding affinities with hGS indicating that Tetrapleura tetraptera is a potential source of new plant-based bioactives relevant in the therapy of neurodegenerative diseases.

Abatement of neurobehavioral and neurochemical dysfunctions in cerebral ischemia/reperfusion injury by Tetrapleura tetraptera fruit extract.

ETHNOPHARMACOLOGICAL RELEVANCE: Tetrapleura tetraptera Taub. (family Fabaceae), is generally found in the lowland forest of tropical Africa. Its leaves and fruits are traditionally used in West Africa for the management of brain disorders. AIM OF THE STUDY: This study evaluated the effect of Tetrapleura tetraptera methanol fruit extract (TT) on bilateral common carotid artery occlusion-induced cerebral ischemia/reperfusion (I/R) injury in male Wistar rats. MATERIALS AND METHODS: Rats pretreated with TT for 7 days before a 30 min bilateral common carotid artery occlusion and reperfusion for 24 h were assessed for neurobehavioural deficits. Cortical, striatal and hippocampal oxidative stress, pro-inflammatory events, electrolyte imbalance and neurochemical dysfunctions, as well as hippocampal histopathological alterations, were also evaluated. HPLC-DAD analysis was performed to identify likely compounds contributing to the bioactivity of the extract. RESULTS: TT reduced I/R-induced behavioral deficits and ameliorated I/R-induced oxidative stress by restoring reduced glutathione level, increasing catalase and superoxide dismutase activities, and also reducing both lipid peroxidation and xanthine oxidase activity in the brain. TT attenuated I/R-increased myeloperoxidase and lactate dehydrogenase activities as well as disturbances in Na+ and K+ levels. Alterations elicited by I/R in the activities of Na+/K+ ATPase, complex I, glutamine synthetase, acetylcholinesterase, and dopamine metabolism were abated by TT pretreatment. TT prevented I/R-induced histological changes in the hippocampus. HPLC-DAD analysis revealed the presence of aridanin, a marker compound for Tetrapleura tetraptera, and other phytochemicals. CONCLUSIONS: These findings indicate that Tetrapleura tetraptera fruit has a protective potential against stroke through modulation of redox and electrolyte imbalances, and attenuation of neurotransmitter dysregulation and other neurochemical dysfunctions. Tetrapleura tetraptera fruit could be a promising source for the discovery of bioactives for stroke therapy.

Toxicological and pharmacological assessment of a multiherbal phytopharmaceutical on Triton X-1339-induced hyperlipidemia and allied biochemical dysfunctions.

This study investigated the safety and therapeutic effect of a multiherbal tea (MHT) on Triton X-1339-induced hyperlipidemia and associated biochemical and tissue dysfunctions. An infusion of the MHT was assessed for phytoconstituents, proximate and mineral composition, and antioxidant activity. Wistar rats administered 200 mg/kg Triton X-1399 were post-treated with MHT for 14 days followed by biochemical estimations in serum, heart, liver, and kidney of animals. Hematological and histopathological evaluations of the blood, and liver, respectively, were also performed. Different phytochemicals were detected in MHT, toxic metals were absent and antioxidant activity was appreciable. Disturbances in glucose level and redox homeostasis, alterations in liver, kidney, and heart function markers, and imbalances in hematological parameters precipitated by triton toxicity were mitigated by posttreatment with MHT. Multiherbal tea also ameliorated triton-induced hepatic histoarchitectural abnormalities. These results suggest that MHT is apparently an effective antilipemic tea with minimal or no side effects. PRACTICAL APPLICATIONS: Hyperlipidemia is one of the core risk factors for arteriosclerosis and a major contributor to other adverse health conditions. The prevalence of hyperlipidemia has increased drastically in the last few decades. Plant and plant products have been extensively used in the management of dyslipidemia and many plant-based antilipemic products with poorly defined toxicity and pharmacological profiles abound in the market. The results of this study demonstrated the protective effects of a MHT against triton-induced hyperlipidemia, atherogenic tendency, and dysfunction of key organs in rats and lent credence to its therapeutic relevance in the management of hyperlipidemia and related diseases.

Ameliorative effect of quercetin, catechin, and taxifolin on rotenone-induced testicular and splenic weight gain and oxidative stress in rats.

Background The physiological functions of the testis and spleen can be affected through several cellular and molecular mechanisms such as the generation of reactive oxygen species (ROS) that causes oxidative stress. This study aimed at investigating the protective effect of catechin, quercetin, and taxifolin in rotenone-induced testicular and splenetic toxicity. Methods Male Wistar rats were administered with 1.5 mg/kg rotenone (s.c.) for 10 days followed by post-treatment with catechin (5, 10, or 20 mg/kg), quercetin (5, 10, or 20 mg/kg), and taxifolin (0.25, 0.5, or 1.0 mg/kg) for 3 days (s.c.), followed by estimation of biochemical markers of oxidative stress, inflammatory activities, and tissue damage in testes and spleen. Results Exposure of rats to rotenone caused reduced body weight gain, increased organ weight, decreased glutathione level and activities of glutathione transferase and superoxide dismutase, enhanced lipid peroxidation, and increased activities of prooxidant/proinflammatory enzymes and lactate dehydrogenase, which were mitigated by post-treatment with flavonoids. In general, quercetin and taxifolin showed better activity than catechin. Conclusions Catechin, quercetin, and taxifolin ameliorated rotenone-induced weight disturbances and oxidative damage in rats, indicating their potential relevance in toxicant and pesticide-induced tissue injury.

Antidiabetic property of miracle fruit plant (Synsepalum dulcificum Shumach. & Thonn. Daniell) leaf extracts in fructose-fed streptozotocin-injected rats via anti-inflammatory activity and inhibition of carbohydrate metabolizing enzymes.

ETHNOPHARMACOLOGICAL RELEVANCE: Miracle fruit plant (Synsepalum dulcificum) has many applications in folk medicine. The leaves are used traditionally to treat diabetes and other diseases. The antidiabetic potential of Synsepalum dulcificum leaves in rats has been studied but the mechanisms involved are yet to be elucidated. AIM: The present study aimed to provide insight into the antidiabetic mechanisms of methanol and flavonoid-rich leaf extracts of Synsepalum dulcificum (MSD and FSD, respectively). METHODS: In vivo effects of administering 30 mg/kg or 60 mg/kg MSD and FSD for 21 consecutive days to rats after type II diabetes was induced through 14 days of fructose feeding and injection of one dose of streptozotocin, were assessed. Glibenclamide (5 mg/kg) served as the reference drug. In addition, in vitro inhibitory activity of MSD and FSD on the carbohydrate metabolizing enzymes, α-amylase and glucokinase, were evaluated, with acarbose as the reference drug. Moreover, in silico analyses to elucidate the contribution of key polyphenolics to the antidiabetic activity of the extracts through docking with glucokinase were performed. RESULTS: MSD and FSD significantly reduced HbA1c and serum levels of interleukin-6 and TNF-α (p < 0.05) in diabetic animals. Conversely, serum level of insulin and hepatic hexokinase activity were increased (p < 0.05) in extract treated groups. Both extracts showed α-amylase and α-glucosidase inhibitory activities. Quercetin, caffeic acid and chlorogenic acid in extracts showed strong binding affinities with glucokinase in the molecular docking analyses. CONCLUSION: Results from this study indicate that increased insulin synthesis, reduction of inflammation and inhibition of carbohydrate metabolizing enzymes are likely mechanisms by which MSD and FSD exert antidiabetic action in type II diabetic rats.

Neurotherapeutic potential of kolaviron on neurotransmitter dysregulation, excitotoxicity, mitochondrial electron transport chain dysfunction and redox imbalance in 2-VO brain ischemia/reperfusion injury.

This study investigated the effects of post-treatment with kolaviron on a 2-Vessel Occlusion (2-VO) model of cerebral ischemia/reperfusion (I/R) injury in rats to ascertain its level of efficacy as a potential therapeutic agent for stroke. Male Wistar rats submitted to 30 min of bilateral common carotid artery occlusion and 24 h of reperfusion were treated with kolaviron (25-100 mg/kg) or 20 mg/kg quercetin immediately after reperfusion and 2 h post reperfusion. At the end of the period of reperfusion, animals were scored for motor and cognitive deficits. Brain relative weight and water content were determined. Cortices, striata and hippocampi were dissected and processed for estimation of markers of oxidative stress, inflammation, neurotransmitter dysregulation and excitotoxicity. In addition, assessment of hippocampal mitochondrial integrity and histopathological examination of the cortical, striatal and hippocampal regions were carried out. There was reversal of 2-VO ischemia/reperfusion (I/R) induced motor and cognitive deficits by kolaviron post-treatment. Post-treatment with kolaviron also attenuated I/R-induced oxidative stress, neuroinflammatory events, excitotoxicity as well as mitochondrial dysfunction in brain tissues. Histopathological findings showed amelioration of I/R-induced neuronal cell damage by kolaviron post-treatment. The results revealed the multi-target neurotherapeutic activity of kolaviron and suggest that it is a promising candidate for drug development against stroke.

Catechin, quercetin and taxifolin improve redox and biochemical imbalances in rotenone-induced hepatocellular dysfunction: Relevance for therapy in pesticide-induced liver toxicity?

Hepatotoxicity occurs as a result of adverse effects of some xenobiotics on the liver, which is often the target tissue of toxicity for environmental chemicals. Rotenone, used as a natural pesticide, is an environmental poison reported to cause organ toxicity. This study investigated the protective effect of three flavonoids, catechin, quercetin and taxifolin (2,3-Dihydroquercetin) in rotenone-induced hepatotoxicity. Male Wistar rats were administered rotenone for 10 days followed by post treatment with catechin (5, 10 and 20 mg/kg), quercetin (5, 10 and 20 mg/kg) or taxifolin (0.25, 0.5 and 1 mg/kg), respectively, for 3 days. Bioindices of oxidative stress and hepatocellular injury were measured in serum and tissue homogenate of animals. Rotenone intoxication produced liver damage in rats as reflected in alterations to activities/levels of enzymic and non-enzymic oxidative stress markers and enzymes linked with inflammation, as well as the transaminases, gamma glutamyl transpeptidase, bilirubin, and lactate dehydrogenase. Catechin, quercetin and taxifolin post treatment significantly attenuated these (p < 0.0001) rotenone-induced imbalances. Comparatively, quercetin displayed the best apparent ameliorative activity. It clearly showed superior activity to catechin. However, taxifolin appeared to show comparable activity to quercetin and better activity than catechin in some of the assays despite being administered at considerably lower doses. The results provide insight on the relative efficacy and structure-activity relationships of the selected flavonoids in ameliorating liver damage and also indicate that additional structural and metabolic factors may be involved in the structure-activity relationships of flavonoids.

Sausage tree (Kigelia africana) flavonoid extract is neuroprotective in AlCl3-induced experimental Alzheimer's disease.

Alzheimer's disease (AD) is a developmental neurodegenerative disorder for which there is no effective treatment or cure at present. In this study, the neuroprotective properties of a methanol extract of the leaves of Kigelia africana (KAE) and its flavonoid-rich fraction (FKAE) in aluminum chloride (AlCl3)-induced experimental AD was evaluated. Symptoms mimicking AD were induced in male Sprague Dawley rats by administering 17mg/kg AlCl3, orally, for six consecutive weeks. Pretreatment of animals with 50 and 100mg/kg KAE or FKAE for two weeks, followed by their co-administration with AlCl3 for a further four weeks ameliorated neurological deficits, cerebral oxidative stress, neurochemical disturbances and histoarchitectural alterations caused by AlCl3 intoxication. The results suggest that KAE and FKAE are promising therapeutic agents for AD.

MODULATION OF KEY BIOCHEMICAL MARKERS RELEVANT TO STROKE BY ANTIARIS AFRICANA LEAF EXTRACT FOLLOWING CEREBRAL ISCHEMIA/REPERFUSION INJURY.

BACKGROUND: Oxidative stress plays a significant role in stroke pathogenesis. Hence, plants rich in antioxidant phytochemicals have been suggested as effective remedies for prevention and treatment of stroke and other neurological diseases. Antiaris africana Engl. (Moraceae) is traditionally used for the management of brain-related problems but there is paucity of data on its anti-stroke potential. MATERIALS AND METHODS: Ischemia/reperfusion injury was induced by a 30 min bilateral common carotid artery occlusion/ 2 h reperfusion (BCCAO/R) in the brain of male Wistar rats. A sham-operated group which was not subjected to BCCAO/R and a group subjected to BCCAO/R without treatment with MEA served as controls. The ameliorative effect of 14 days of pretreatment with 50 mg/kg or 100 mg/kg A. africana methanol leaf extract (MEA) on BCCAO/R-mediated alterations to key markers of oxidative stress (malondialdehyde, reduced glutathione, xanthine oxidase, superoxide dismutase, catalase and glutathione peroxidase) and neurochemical disturbances and excitotoxicity (myeloperoxidase, glutamine synthetase, Na+/K+ ATPase, acetylcholinesterase and tyrosine hydroxylase), was evaluated and compared with the effect produced by treatment with 20 mg/kg quercetin as a reference standard. RESULTS: Results show that pretreatment with MEA significantly mitigated or reversed BCCAO/R-induced changes in the level or activity of the evaluated biochemical markers of oxidative stress, neurochemical dysfunction and excitotoxicity compared with the BCCAO/R untreated control group (p < 0.05). The effect produced by 100 mg/kg MEA was similar to that of the reference standard, quercetin. CONCLUSION: These results revealed the neuroprotective potential of A. africana in stroke and other ischemia-related pathologies.

Effect of homopterocarpin, an isoflavonoid from Pterocarpus erinaceus, on indices of liver injury and oxidative stress in acetaminophen-provoked hepatotoxicity.

BACKGROUND: Novel hepatoprotectives are needed to address the increasing cases of liver problems worldwide. Pterocarpus erinaceus Poir (Fabaceae) ethanol stem bark extract (PE) and its constituent flavonoid, homopterocarpin (HP), were investigated for their protective property in acetaminophen-induced oxidative stress and liver damage. METHODS: Adult male albino rats were divided into nine groups. Seven groups were pretreated with PE (50-, 100-, and 150 mg/kg), HP (25-, 50-, and 75 mg/kg) or silymarin (25 mg/kg), respectively, once daily for 5 consecutive days and then administered acetaminophen (2 g/kg) on the 5th day. The control and acetaminophen-intoxicated groups received normal saline throughout the experimental period, with the latter group additionally receiving 2 g/kg acetaminophen on the 5th day. Administrations were performed po. RESULTS: In the acetaminophen-intoxicated group, there were significant increases (p<0.05) in serum activities of alanine aminotransferase (31.72±3.3 vs. 22.1±1.2 U/I), aspartate aminotransferase (185.1±10.1 vs. 103.83±13.3 U/I), bilirubin level and hepatic malondialdehyde (2.32±0.3 vs. 1.42±0.1 units/mg protein), accompanied with significant decreases (p<0.05) in hepatic reduced glutathione level (0.10±0.01 vs. 0.23±0.03 units/mg protein) and glutathione peroxidase activity (2.51±0.2 vs. 3.25±0.2 µmol H2O2 consumed/min/mg protein) compared with the control. CONCLUSIONS: PE and HP ameliorated most of the observed biochemical alterations with HP appearing to show more potency. The results suggest that the flavonoid, homopterocarpin contributes to the hepatoprotective and antioxidant potentials of P. erinaceus extract.

Kolaviron, a Garcinia kola biflavonoid complex, protects against ischemia/reperfusion injury: pertinent mechanistic insights from biochemical and physical evaluations in rat brain.

The pathophysiology of stroke is characterized by biochemical and physical alterations in the brain. Modulation of such aberrations by therapeutic agents affords insights into their mechanism of action. Incontrovertible evidences that oxidative stress is involved in the pathophysiology of neurologic disorders have brought antioxidative compounds, especially plant phytochemicals, under increasing focus as potential remedies for the prevention and management of neurodegenerative diseases. Kolaviron, a biflavonoid complex isolated from Garcinia kola Heckel (Guttiferae) was evaluated for neuroprotectivity in brains of male Wistar rats submitted to bilateral common carotid artery occlusion-induced global ischemia/reperfusion injury (I/R). Animals were divided into six groups: sham treated, vehicle (I/R), 50 mg/kg kolaviron + I/R, 100 mg/kg kolaviron + I/R, 200 mg/kg kolaviron + I/R and quercetin (20 mg/kg i.p.) + I/R. The common carotid arteries were occluded for 30 min followed by 2 h of reperfusion. Relative brain weight and brain water content were determined and oxidative stress and neurochemical markers were also evaluated. I/R caused significant decreases in glutathione level and the activities of enzymic antioxidants, the sodium pump and acetylcholinesterase while significant increases were recorded in relative brain weight, brain water content, lipid peroxidation and the activities of glutamine synthetase and myeloperoxidase. There was a remarkable ablation of I/R induced oxidative stress, neurochemical aberrations and brain edema in animals pretreated with kolaviron. The results suggested that the protection afforded by kolaviron probably involved regulation of redox and electrolyte homeostasis as well as anti-inflammatory and antiexcitotoxic mechanisms.

Homopterocarpin contributes to the restoration of gastric homeostasis by Pterocarpus erinaceus following indomethacin intoxication in rats.

OBJECTIVE: To investigate the restorative effect of Pterocarpus erinaceus (P. erinaceus) and homopterocarpin, an isoflavonoid isolated from it, on indomethacin-induced disruption in gastric homeostasis in rats. METHODS: Adult rats were divided into five groups and fasted for 48 h before treatment. Group 1 received olive oil (vehicle), group 2 received 25 mg/kg indomethacin while groups 3-5 received cimetidine (100 mg/kg), homopterocarpin (25 mg/kg) and P. erinaceus ethanolic stem bark extract (100 mg/kg) respectively. After 1 h, all the groups except group 2 were administered 25 mg/kg of indomethacin. One hour later, the rats were sacrificed and the ulcer index and other gastroprotective indices were evaluated. RESULTS: Indomethacin caused significant injury to the stomach of the rats as reflected in the ulcer indices (9.0±1.4) as compared with that of control (2.0±0.0). Equally, there were significant increases in gastric acid concentration and malondialdehyde level in the stomachs of the ulcerated animals compared with the control. However mucus content, reduced gluthatione level and gastric pH were significantly reduced in the ulcerated animals compared with the control. Pretreatment with either Pterocarpus bark extract or homopterocarpin reversed the effects of indomethacin on the evaluated parameters. CONCLUSIONS: These results indicate that both homopterocarpin and Pterocarpus extract offered gastroprotection against indomethacin-induced ulcer by antioxidative mechanism and the modulation of gastric homeostasis. The results also suggest that homopterocarpin might be responsible for, or contribute to the antiulcerogenic property of P. erinaceus.

Antioxidant activity and hepatoprotective property of leaf extracts of Boerhaavia diffusa Linn against acetaminophen-induced liver damage in rats.

Extracts of Boerhaavia diffusa leaves were evaluated for antioxidant and hepatoprotective properties in the acetaminophen-induced liver damage model. Antioxidative evaluation of ethanolic extract gave total phenolic content, total flavonoid content, vitamin C content and vitamin E content and the levels of selenium and zinc as 6.6+/-0.2mg/g tannic acid equivalent, 0.092+/-0.003 mg/g quercetin equivalent, 0.21+/-0.03 mg/g, 0.054+/-0.002 mg/g, 0.52+/-0.05 ppm and 9.28+/-0.16 ppm, respectively. The DPPH scavenging capacity and the reductive potential were 78.32+/-2.41% and 0.65+/-0.02 mg/g ascorbic acid, respectively. Pretreatment with aqueous and ethanolic extracts decreased the activities of alkaline phosphatase, lactate dehydrogenase, alanine aminotransferase, aspartate aminotransferase, and the level of bilirubin in the serum that were elevated by acetaminophen. The two extracts also ameliorated the elevation in the activities of the enzymes in the liver. Acetaminophen intoxication led to reduction in serum and liver albumin levels which were not significantly increased by pretreatment with the extracts. The extracts also protected against acetaminophen induced lipid peroxidation. These results indicated that leaf extracts from B. diffusa possess hepatoprotective property against acetaminophen-induced liver damage which may be mediated through augmentation of antioxidant defenses.

Acetaminophen-induced liver damage in mice: effects of some medicinal plants on the oxidative defense system.

Paracetamol (acetaminophen, PCM) is widely used as an over-the-counter analgesic and antipyretic drug. Intake of a large dose of PCM may result in severe hepatic necrosis. Oxidative stress mediated by oxidative capacities of the PCM metabolite (N-acetyl-p-benzoquinoneimine (NAPQI), is considered as the main cause of hepatotoxicity of PCM. This work therefore seeks to induce liver damage in mice using single dose (25 0mg/kg) of acetaminophen and to evaluate the possible protective effects of administration (100mg/kg) of some medicinal plants (Kigelia africana, Calotropis procera, Hibiscus sabdariffa and Alchornea cordifolia) on PCM-induced liver damage in mice. The alanine aminotransferase (ALT), and aspartate aminotransferase (AST) activities were determined in the plasma of mice. Equally, comparative effects of these plants on lipid peroxidation product thiobarbituric reacting substances (TBARS) and some antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), gluthathione peroxidase (GPx), and delta-aminolevulinate dehydratase (delta-ALA-D) activities, were also evaluated in the mouse liver homogenate. Paracetamol caused liver damage as evident by statistically significant (P<0.05) increased in plasma activities of AST and ALT. There were general statistically significant losses in the activities of SOD, GPx, CAT, and delta-ALA-D and an increase in TBARS in the liver of paracetamol-treated group compared with the control group. However, all the tested plants except Calotropis procera were able to counteract these effects. The present results suggest that these plants can act as hepatoprotectives against paracetamol toxicity and that the mechanism by which they do this is by acting as antioxidants.