Afolabi C. Akinmoladun

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.

Evaluation of Antioxidant and Free Radical Scavenging Capacities of Some Nigerian Indigenous Medicinal Plants

Methanolic extracts of 10 selected Nigerian medicinal plants-Psidium guajava, Alstonia boonei, Cassia alata, Newbouldia laevis, Spondias mombin, Globimetula cupulatum, Chromolaena odorata, Securidaca longepedunculata, Ocimum gratissimum, and Morinda lucida-widely used in ethnomedicine, were assessed for phytochemical constituents and antioxidant and free radical scavenging activities using seven different antioxidant assay methods. Phytochemical screening gave positive tests for steroids, terpenoids, and cardiac glycosides, alkaloids, saponins, tannins, and flavonoids contained in the extracts. P. guajava contained the highest amount of total phenolics (380.08 +/- 4.40 mg/L gallic acid equivalents), and the highest amounts of total flavonoids were found in the leaf extracts of C. alata (275.16 +/- 1.62 microg/mL quercetin equivalents [QE]), C. odorata (272.12 +/- 2.32 microg/mL QE), and P. guajava (269.72 +/- 2.78 microg/mL QE). Percentage 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity was highest in S. mombin (88.58 +/- 3.04%) and P. guajava (82.79 +/- 2.84%) and compared with values obtained for ascorbic acid and gallic acid. All the extracts, generally, had low nitric oxide radical scavenging activities, and G. cupulatum had the highest hydroxyl radical scavenging activity (63.84 +/- 0.97%). The extracts in general demonstrated high lipid peroxidation inhibitory activity, with only M. lucida (38.74 +/- 1.99%) and A. boonei (47.16 +/- 0.59%) being exceptions. The reductive potential was highest in P. guajava (0.79 +/- 0.04) and least in S. longepedunculata (0.26 +/- 0.00). DPPH assay correlated well with total phenolic contents (r(2) = 0.76) and reductive potential (r(2) = 0.81) and fairly with lipid peroxidation inhibitory activity (r(2) = 0.51). There was a good correlation between total phenolic contents and reductive potential (r(2) = 0.79) and a fair correlation between total phenolic contents and lipid peroxidation inhibitory activity (r(2) = 0.55). These results suggest that the methanolic extracts of the studied plant parts possess significant antioxidant and radical scavenging activities that may be due to the phytochemical content of the plants and as such make them potential candidates as natural chemoprophylactic agents. In addition, multiple assay methods should be used in comparing antioxidant capacities of samples to have a reliable result.

Rutin and quercetin show greater efficacy than nifedipin in ameliorating hemodynamic, redox, and metabolite imbalances in sodium chloride-induced hypertensive rats

Rutin and quercetin were investigated for their effects on blood pressure and antioxidant defense system of rats fed with 8% sodium chloride-supplemented diet (high salt diet) for 6 weeks. Animals fed with high salt diet demonstrated an increase in systolic, diastolic, pulse, and mean arterial blood pressures (p < 0.05) as well as lipid peroxidation but decreases in the activities of antioxidant enzymes compared with control group. Groups post-treated with rutin and quercetin for 2 weeks showed significant reversals in the values of these indices compared with the group fed with only the high salt diet but not post-treated. The high salt diet also led to significant increase in serum glucose, urea, creatinine, triglycerides, low-density-lipoprotein, and total cholesterol concentrations. Treatment with rutin and quercetin ameliorated the effects of high salt diet on these biochemical indices. The reference standard, nifedipin was less effective than rutin and quercetin. The results of this study highlight the risk of high salt consumption on cardiovascular health and the potent antioxidant and antihypertensive property of rutin and quercetin.

Comparative gastroprotective effect of post-treatment with low doses of rutin and cimetidine in rats

The anti‐ulcerogenic potentials of low doses of rutin and cimetidine in ethanol‐, acetic acid‐, and stress‐induced ulcers in rats have been evaluated and compared in this study. In each model, male Wistar rats were randomly divided into six groups (I–VI). Groups II–VI were administered 1 mL/100 g ethanol orally, 0.05 mL of 20% acetic acid submucosally or kept in a cold chamber for 6 h to induce ulcer in the ethanol‐, acetic acid‐, and stress‐induced ulceration model, respectively. Thereafter, group III was post‐treated with 300 mg/kg cimetidine and groups IV–VI with 20, 40, and 80 mg/kg rutin, respectively, while the control (group I) received distilled water in Tween 20. One hour after post‐treatment, all groups were killed and the gastric ulcer index was calculated. Malondialdehyde (MDA) level, vitamin C content, and glutathione peroxidase (GPx) activity were evaluated in the gastric mucosa of animals. Post‐treatment with rutin significantly reduced ulcerogen‐induced gastric damage in all models. This effect was significant at all dose levels compared with the ulcer‐induced groups. Rutin significantly reduced the MDA levels but increased the vitamin C content and GPx activity. Ulcer index and MDA level were highest in the ethanol‐induced ulcer model while vitamin C content and GPx activity were lowest in the stress‐induced ulcer model. The study showed that all three models of ulceration appeared to be linked to oxidative stress and also ascribed significant anti‐ulcerogenic potential to rutin especially at lower doses of 20–80 mg/kg.

Redox status and sperm characteristics in 1,4-dinitrobenzene-induced reproductive toxicity in Wistar rats

Abstract1,4-Dinitrobenzene (1,4-DNB) is a synthetic compound used in explosives, dyes, organic chemicals and the plastic industry. Oral and dermal exposure is a likely route for industrial workers and people living near ammunition plants. This study investigated the effect of 1,4-DNB on testicular and spermatozoan antioxidant systems as well as sperm characteristics of Wistar rats. Oral exposure of male Wistar rats to 50 or 75 mg/kg, or dermal exposure to 1000 or 2000 mg/kg, of 1,4-DNB for 14 days increased spermic and testicular hydrogen peroxide and lipid peroxidation levels accompanied by decreased activities of enzymic antioxidants. Exposure to 1,4-DNB also resulted in decrease in body weight gain, reduced testicular and epididymal weights, epididymal degeneration, decrease in sperm quantity and quality, and mild congestion of interstitial vessels and edema in the testes. These results reveal that individuals unduly exposed to 1,4-DNB risk induction of oxidative stress in the epididymis and testis, and associated reproductive deficits.

Xeronine structure and function: computational comparative mastery of its mystery

Morinda citrifolia (Noni) fruit has a long history of dietary use in tropical regions of the world. Pharmacological properties that have been attributed to the fruit include anti-inflammatory, anti-cancer, and antioxidant properties. Xeronine, a small alkaloid which has been patented (US4543212) is one of the bioactive compounds of Noni fruit, which is believed to be capable of modifying the molecular structure of specific inactive proteins thereby regulating proper folding to active enzymes. Despite reports of the potential of Xeronine as therapeutic agent, its presence is controversial and its structure has not been explored. In this study, standard chemoinformatics tools and servers such as ChemSketch, ChemMine, Swisstargetprediction, SwissADME and Swisssimilarity have been employed to predict its possible structure. In addition, synthetic xeronine structures based on the known bioactive components of Noni fruit were designed. Results showed that the hypothetical structure of xeronine provided by the patent inventor is a mystery based on its <5% probable protein targets and no similarity match to the US Food and Drug Administration (FDA) approved drugs and experimental compounds by in silico evaluation. By constrast, final designed xeronine structure possess all the features that were described in the patent document, and has >40% probable protein targets related to neurodegenerative diseases such as Alzheimer’s disease (AD), which possibly justifies the key function stated in the patent.

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.

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.

Modulatory effect of Psidium guajava Linn and Ocimum gratissimum Linn on lipid profile and selected biochemical indices in rabbits fed high cholesterol diet.

The effect of aqueous leaf extracts of Psidium guajava(PG) and Ocimum gratissimum(OG) on fasting plasma glucose (FPG), total protein (TP), albumin (ALB), globulin (GLB), total cholesterol (TC), triglyceride (TG), HDL-cholesterol (HDL), LDL-cholesterol (LDL) and lactate dehydrogenase (LDH) concentrations in rabbits fed high-cholesterol diet was investigated. Four groups of animals were used (n = 6). Animals in group A were fed normal laboratory pellet and water ad libitum; those in group B were fed the high-cholesterol diet (normal diet + 1% w/w cholesterol + 1% w/w vegetable oil) while those in groups C and D received a daily oral administration of 250 mg/kg body weight of the extract of Psidium guajava and Ocimum gratissimum, respectively, in addition to the high-cholesterol diet for a period of six weeks. Hypercholesterolemia, associated with hyperglycemia was induced significantly in animals in group B compared to normal control group (A) (P<0.01). There were also significant increases in the levels of LDL (P<0.05) and HDL (P<0.01). Treatments with PG and OG reduced the plasma cholesterol level by 15% and 28%, respectively, compared to animals in Group B. PG caused a remarkable increase in HDL (69%) but a decrease in LDL (74%) levels. OG on the other hand reduced the levels of both HDL and LDL by 50% and 26%, respectively, compared to animals in Group B. While the level of HDL in the OG group was similar to that of normal controls, the LDL level was significantly higher (71%). Furthermore, both extracts reduced the associated hyperglycemia significantly (P<0.05). This decrease was more pronounced in PG treated rabbits (PG; 43%, OG; 19%). In addition, OG stimulated a significant increase in the concentrations of LDH and serum protein, particularly albumin. These results show that aqueous extracts of both plants especially PG ameliorated the hypercholesterolemic and associated hyperglycemic effects of high cholesterol diet. However, OG shows possible contraindications and the safety of its ethnomedical usage warrants further investigation.

Improvement of 2-Vessel Occlusion Cerebral Ischaemia/Reperfusion-Induced Corticostriatal Electrolyte and Redox Imbalance, Lactic Acidosis and Modified Acetylcholinesterase Activity by Kolaviron Correlates with Reduction in Neurobehavioural Deficits

Background: Disruption of electrolyte, redox and neurochemical homeostasis alongside cellular energy crisis is a hallmark of cerebral ischaemia and reperfusion injury. Purpose: This study investigated the effect of kolaviron (KV) on cortical and striatal cation imbalance, oxidative stress and neurochemical disturbances as well as neurobehavioural deficits in animals subjected to bilateral common carotid artery occlusion (BCCAO)-induced ischaemia/reperfusion injury. Methods: KV was administered at a dose of 100 or 200 mg/kg to male Wistar rats 1 h before a 30 min BCCAO/4 h reperfusion (I/R). This was followed by neurobehavioral assessment and biochemical evaluations of cation levels, oxidative stress indicators, lactate dehydrogenase activity and acetylcholinesterase (AChE) activity in the brain of animals. Conclusion: KV significantly restored altered cortical and striatal Ca2+, Na+, K+ and Mg2+ levels, ameliorated redox imbalance, lactic acidosis and modified AChE activity caused by I/R injury. The favourable neurobehavioural effects of KV correlated with biochemical outcomes. The pharmacological potential of KV in the treatment and management of ischemic stroke and allied pathological conditions via multiple targets (neurotransmitter metabolism, bioenergetic failure and ionic homeostasis) is highlighted by the study.