Safety and Efficacy of Methanol Fraction of Moringa oleifera as Antihypertensive in L-NAME Induced Hypertensive Rabbits: Bedside to Bench, Implications for Bench Back to Bedside

Context: Hypertension, a global menace requires innovative research into the use of Moringa oleifera being promoted and traditionally used as alternative therapy.Objective: To innovatively evaluate the mechanistic effect, safety and efficacy of the methanol fraction of M. oleifera (MMO) leaves on L-NAME induced hypertensive rabbits.Methods: Rabbits were divided into six groups: Control, L-NAME alone, L-NAME with 100, 200 or 400 mg/kg of MMO and enalapril. Inclusion and exclusion criteria were similar baseline parameters and Day 3 systolic blood pressure (SBP) less than baseline SBP respectively. The primary outcome was a 10% reduction of SBP on Day 21. Enalapril group was excluded from analysis. Safety was assessed with liver and renal functions, hydrogen peroxide and nitric oxide concentrations to elucidate mechanistic effect.Results: Moringa 100 mg/kg, 200 mg/kg and 400 mg/kg reduced SBP by 4.75, 18.00 and 15.25 mmHg (F=22.123, p=0.000). SBP control was achieved with MMO 200mg/kg, 14% reduction and 400mg/kg, 12% reduction. Nitric oxide concentration, 0.06, 0.094 and 0.114mmol (F= 30.255, p= 0.000) dose-dependently increased and was most predictive of SBP control (r2=0.802, p=0.000). Nitric oxide production was inversely related to heart/body weight ratio which was dose-dependently reduced. MMO reduced hydrogen peroxide and ALT level but no significant effect on urea, HDL, and TG.Conclusion: MMO reduced SBP and dose-dependently increased nitric oxide concentration in L-NAME induced hypertensive rabbits. The effect may be mediated via activation of nitric oxide pathway. MMO demonstrated a potent anti-oxidant activity and safety. Effect on ventricular hypertrophy needs further evaluation

The Pharmaceutical Properties, Microbial Quality, In-vivo Aphrodisiac Effect and Safety of Some Herbal Bitters Sold in Southwest Nigeria

Aphrodisiac drugs are used to enhance sexual activity and rectify erectile dysfunction especially among older men. In Nigeria, herbal medicinal products formulated as herbal drinks/bitters are prevalent and sold in various locations including motor parks, store and markets. Despite their wide use, the potency and safety of the herbal drinks have not been ascertained. Thus, pharmaceutical and aphrodisiac properties of five randomly selected herbal drinks with aphrodisiac claim have been evaluated. Pharmaceutical and microbial qualities were evaluated using standard procedures and the in vivo aphrodisiac activities were evaluated in male Wistar rats. The effects of chronic consumption of the bitters on the biochemical and tissue histology were assessed. The herbal bitters exhibited low viscosity (< 10 cP), high alcohol content (30 – 52 %), acidic pH (3.33 - 5.40), and low density (0.942-1.070 g/ml). The phytoconstituents include alkaloids, flavonoids, saponins, cardenolides, tannins and anthraquinone. Microbial contaminations were with the limits for oral preparations. The bitters exhibited significant (p < 0.001) aphrodisiac effect but had no significant effect on fertility and hematological parameters. Chronic consumption of the herbal drinks at 250mg/kg following was hepatotoxic while two brands were cardiotoxic and nephrotoxic. There is therefore the need to monitor and control the quality and use of herbal bitters/drinks sold in the Nigerian market to safeguard public healt

Ameliorative effects of Cnidoscolus aconitlfolius on alloxan toxicity in Wistar rats

Background: Diabetes has been associated with several complications occasioned by oxidative stress. Thus, in treatment of the condition, these complications must also be taken into consideration. This study evaluates the effect of Cnidoscolus aconitifolius complications of diabetes induced by alloxan, on haematology and sperm morphometty using the Wistar rats. Methods: Diabetes was induced in 25 rats using alloxan. The diabetic rats were then divided into five groups B-F consisting of five rats per group. Groups C-E were administered with 100mg/kg, 500mg/kg and 1000mg/kg of ethanolic leaves extract of Cnidoscolus aconitifolius, respectively, for four weeks post treatment with alloxan, while group F received Chlorpropamide (Diabenes®, Pfizer). The diabetic rats in group B were not treated while group A served as the non diabetic control. Result: Following treatment with alloxan, there was anaemia, thrombocytopenia and leucopenia, while the sperm count, motility and live/dead ratio were significantly reduced. Sperm morphological abnormalities and erythrocyte osmotic fragility also increased significantly. Following treatment of alloxan treated-rats with the extract, there were significant increases in the PCV, RBC, Hb, WBC, MCV and the platelet values. Erythrocyte osmotic fragility, sperm count, motility and live/dead ratio also improved significantly. Conclusion: Cnidoscolus aconitifolius extract was found to ameliorate the effects of alloxan induced diabetes on the haematology but not on the abnormal sperm morphometty in rats

Assessment of Chronic Administration of Aloe Vera Gel On Haematology, Plasma Biochemistry, Lipid Profiles and Erythrocyte Osmotic Resistance in Wistar Rats

The study was designed to investigate the effects of chronic administration of Aloe vera gel extract on markers of hepatic damage, lipid profiles and erythrocyte osmotic fragility using the Wistar rats. Forty male Wistar rats divided into four groups of ten rats per group were used in the study. Group I which served as the control received 0.9% physiological saline while those in groups II, III and IV received Aloe vera gel (100, 250 and 500mg/kg), respectively, for four weeks. There was significant increase in the haemoglobin concentration while the PCV, RBC count, MCH and MCHC though showed some marginal increases but the increases were not significant in all the treated rats. No significant change was also observed in the erythrocyte osmotic fragility. However, there were significant reductions in plasma ALT (P<0.001), AST (P<0.05) and ALP (P<0.05) levels in animals that received the gel compared with the control while the plasma albumin (P<0.01) and total protein (p<0.05) values were higher than those of the control. All the animals that received the gel also showed significant reduction in plasma total cholesterol (P<0.001), triglycerides (P<0.001) and LDL-cholesterol ratio (p<0.01) compared with the control. In a similar manner, those animals that were administered with 500mg/kg gel had significantly higher (P<0.001) HDL-cholesterol ratio than those of the control. This study showed that, chronic administration of Aloe vera gel extract had no significant effects on the haematological parameters of the rats and did not affect erythrocyte osmotic resistance. It however showed some cholesterol lowering action

Short distance transportation stress: effects of ascorbic acid and a-tocopherol on free radical generation and endogenous antioxidant status

The modulatory effect of pre-treatment with ascorbic acid and á-tocopherol on short distance transportation was investigated in the domestic chicken. Thirty-two, adult (20 week old), female Nera black chicken were divided into four groups (A-D) consisting of eight birds per group. Groups A and B were not given any antioxidant while groups C and D were given 650mg/kg and 270mg/kg ascorbic acid and á-tocopherol, respectively in their feed for two weeks. The birds in groups B, C and D were transported over a distance of 200km. Total plasma protein, H2O2 generation, lipid peroxidation and glutathione levels were evaluated in all the birds after transportation. There were no significant differences in the total protein, H2O2 generation, malondialdehyde (MDA) and glutathione (GSH) levels in those birds transported without antioxidant compared with the control. The ascorbic acid group had higher H2O2 and malondialdehyde levels but lower plasma protein and glutathione than the control. However, the á-tocopherol group had higher H2O2 and glutathione levels but lower protein than the control. It is concluded that short distance transportation may not increase oxidative stress and lipid peroxidation in the chicken. Prolonged use of vitamin C and E as antioxidants may however lead to oxidative stress. Vitamin E also appears to improve glutathione level more than Vitamin C.Keywords: Ascorbic acid, Lipid peroxidation, Oxidative stress, Transportation, átocophero

Evaluation of oxidative stress in caprine bronchoalveolar lavage fluid of pneumonic and normal lungs

Research in the area of oxidative stress in pneumonic pathology still requires attention in small ruminants especially with the use of bronchoalveolar lavage (BAL) which may be a more sensitive indicator of respiratory diseases than blood. This investigation evaluates the role of oxidative stress in the pathogenesis of caprine pneumonia using BAL fluid (BALf) from healthy and pneumonic goats. A BALf from 192 goats (whose pneumonic histopathology had been characterized using standard techniques) was biochemically assayed for anti-oxidants and pro-oxidants. Malondialdehyde (MDA), hydrogen peroxide generation (H2O2), myeloperoxidase (MPO) and reduced glutathione (GSH) contents were measured to assess free radical activity in the BALf. Superoxide dismutase (SOD), Glutathione transferase (GST) and Glutathione peroxidase (GPx) activity were also determined colourimetrically. There were significant increases in the BALf supernatant of MDA, H2O2 and MPO with decreases in GSH level and SOD activity in the pneumonic goats (P < 0.05). There was also significant correlation of BALf oxidative assay to the type and severity of pneumonia. The levels of MDA, H2O2, and MPO increased significantly (P < 0.05) in bronchopneumonia and bronchointerstitial pneumonia than other pneumonic conditions and normal lungs. The management of caprine pneumonia should often incorporate antioxidant supplementation to correct the imbalance in pro-oxidant and anti-oxidant levels. Keywords: Anti-oxidants, Pro-oxidants, Pneumonia, Myeloperoxidase, Malondialdehyde, Glutathione transferas

Phytochemical profiling, antioxidant activities and essential oil constituents of Andrographis paniculata

Oxidative stress is involved in the pathogenesis of various diseases which lead to urgent need to investigate new, safe and effective source of antioxidant agents. This research proposed to investigate in-vitro and phytochemical constituent of the plant Andrographis paniculata using phytochemical analysis, GC/MS, DPPH, ABTS, FRAP and NO. Phytochemical analysis of Andrographis paniculata revealed the presence of tannins, total flavonoids, total phenol, total flavonols, and total proanthocyanidins. GC/MS analysis of essential oil of AP identified one major compound name benzenepropanoic acid elucited at 3.296 retention time and 0.74 area percentage. The ferric reducing potential of the extracts was concentration dependent and significantly different from that of rutin and vitamin E. The % inhibition of ABTS by the ethanol leaf extract of Andrographis paniculata was concentration dependent and compared favourably well with the rutin and vitamin E. In DPPH scavenging assays, the IC50 value of the ethanol leaf extract of Andrographis paniculata was &lt; 0.025 mg/ml, while IC50 of rutin and Vitamin E were &lt; 0.025 mg/ml and 0.08mg/ml. Nitric oxide IC50 for extract is 1.05mg/ml, Vitamin E is 1.2 mg/ml, and rutin is &lt; 0.025 mg/ml. The present study showed high level of radical scavenging activity by ethanol leaf extract of Andrographis paniculata with higher antioxidant activities than Vitamin E but less than that of rutin. This show that Andrographis paniculata has antioxidant properties and the plant could be used in the prevention and treatment of diseases associated with oxidative stress.Keywords: Andrographis paniculata, Antioxidants, Oxidative stres

Effect of arsenic acid withdrawal on hepatotoxicity and disruption of erythrocyte antioxidant defense system

We investigated the effects of withdrawal from Sodium arsenite (NaAsO2) on the hepatic and antioxidant defense system in male Wistar rats using a before and after toxicant design. Rats were orally gavaged daily with varying doses of NaAsO2 for a period of 4 weeks. One half of the population was sacrificed and the remaining half had the toxicant withdrawn for another further 4 weeks. Biochemical and immunohistochemical techniques were used to assess the impact of withdrawal on the erythrocyte and hepatic systems. Exposure of Wistar rats to NaASO2 led to a significant (p < 0.05) increase in hepatic and erythrocyte markers of oxidative stress (malondialdehyde, thiol contents and hydrogen peroxide generation). Concurrently, there was a significant (p < 0.05) increase in hepatic and erythrocyte antioxidant enzymes (glutathione-S-transferase, glutathione peroxidase and superoxide dismutase) following exposure. Withdrawal from NaAsO2 exposure led to a decline in both erythrocyte and hepatic markers of oxidative stress and together with a significant improvement in antioxidant defense system. Histopathology and immunohistochemistry revealed varying degrees of recovery in hepatocyte ultrastructure alongside increased expression of the pro-survival protein Kinase B (Akt/PKB) after 4 weeks of NaAsO2 withdrawal. Conclusively, withdrawal from exposure led to a partial recovery from oxidative stress-mediated hepatotoxicity and derangements in erythrocyte antioxidant system through Akt/PKB pathway. Keywords: Liver, Erythrocyte, Arsenic acid, Hepatotoxicity, Oxidative stress, Akt/PKB signalin