Eric K. I. Omogbai

Antifungal and antibacterial activities of the ethanolic and aqueous extract of Kigelia africana (Bignoniaceae) stem bark

Studies on the antibacterial and antifungal activities of the stem bark of Kigelia africana, (LAM). Benth (Family: Bignoniaceae), a medicinal plant used in South, Central and West Africa for the treatment of various ailments and infection was carried out using agar diffusion technique. The results revealed that the crude ethanolic extract exhibited antibacterial and antifungal activities against Staphylococccus aureus and Candida albicans with zones of inhibition measuring 15.0±0.95 and 20.75±4.6mm respectively. The aqueous extract exhibited no antibacterial or antifungal activity. The minimum inhibitory concentration for the extract was 6.25 ± 1.07 mg/ml for S. aureus and 7.92 ± 1.52 mg/ml for C. albicans. The ethanolic extract was also compared with various standards; Ampicillin, Gentamicin, Ceftriaxone and Ciprofloxacin. The ethanolic extract (20mg/ml) produced similar zone of inhibition with 25ig disc of amoxicillin.

Dimethyl fumarate confers neuroprotection by casein kinase 2 phosphorylation of Nrf2 in murine intracerebral hemorrhage

BACKGROUND AND PURPOSE Edema formation, inflammation and increased blood-brain barrier permeability contribute to poor outcomes after intracerebral hemorrhage (ICH). This study examined the therapeutic effect of dimethyl fumarate (DMF), a fumaric acid ester that activates nuclear factor erythroid-2 related factor 2 (Nrf2) and Nrf2 heterodimerization effector protein musculo-aponeurotic fibrosarcoma-G (MAFG) in a murine ICH model. METHODS Male CD-1 mice (n=176) were subjected to intrastriatal infusion of bacterial collagenase (n=126), autologous blood (n=18) or sham surgery (n=32). Four (4) animals not subjected to ICH (naive) were also included in the study. After ICH, animals either received vehicle, dimethyl fumarate (10 mg or 100 mg/kg) or casein kinase 2 inhibitor (E)-3-(2,3,4,5-tetrabromophenyl)acrylic acid (TBCA). Thirty-two mice also received scrambled siRNA or MAFG siRNA 24h before ICH. Brain water content and neurological function were evaluated. RESULTS Dimethyl fumarate reduced Evans blue dye extravasation, decreased brain water content, and improved neurological deficits at 24 and 72 h after ICH. Casein kinase 2 inhibitor TBCA and MAFG siRNA prevented the effect of dimethyl fumarate on brain edema and neurological function. After ICH, ICAM-1 levels increased and casein kinase 2 levels decreased. Dimethyl fumarate reduced ICAM-1 but enhanced casein kinase 2 levels. Again, casein kinase 2 inhibitor TBCA and MAFG siRNA abolished the effect of dimethyl fumarate on ICAM-1 and casein kinase 2. Dimethyl fumarate preserved pNrf2 and MAFG expression in the nuclear lysate after ICH and the effect of dimethyl fumarate was abolished by casein kinase 2 inhibitor TBCA and MAFG siRNA. Dimethyl fumarate reduced microglia activation in peri-hematoma areas after ICH. The protective effect of dimethyl fumarate on brain edema and neurological function was also observed in a blood injection mouse model. CONCLUSION Dimethyl fumarate ameliorated inflammation, reduced blood-brain barrier permeability, and improved neurological outcomes by casein kinase 2 and Nrf2 signaling pathways after experimental ICH in mice.

In vitro determination of the uterine stimulatory effect of the aqueous leaf extract of Ficus exasperata

ETHNOPHARMACOLOGICAL RELEVANCE The leaves of Ficus exasperata Vahl (Moraceae) are used by traditional healers in Southern Nigeria to arrest pre-term contractions and are also used as an abortifacient in some parts of Africa. AIM OF STUDY An earlier study on the aqueous leaf extract of Ficus exasperata (AET) showed that the extract at lower concentrations inhibited oxytocin-induced uterine contractions and at higher concentrations, stimulated uterine contraction. This study thus aims to determine, the possible mechanisms by which AET stimulates uterine contraction in vitro. MATERIALS AND METHODS The contractile effect of AET (5.0 x 10(-2) to 100 x 10(-2)mg/ml) and oxytocin (which was used as a reference drug) were examined in the presence of the following antagonists: atropine (1.18 and 11.91 nM); indomethacin (1.42 and 14.25 nM); verapamil (2.03 and 20.35 nM); phentolamine (4.09 and 40.91 nM), or diphenhydramine (4.45 and 44.47 nM). The EC(50) and E(max) were determined and statistically analyzed using one-way ANOVA and Dunnett post hoc test. RESULTS There was no significant difference in the EC(50) and E(max) of AET and oxytocin in the presence of atropine. Diphenhydramine and phentolamine significantly inhibited (p<0.01) the extract but both drugs had no effect on oxytocin. However, significant differences (p<0.01) were observed in the EC(50) and E(max) of AET and oxytocin in the presence of verapamil and indomethacin. CONCLUSIONS These results suggest that the stimulation of uterine contractility by AET may arise from the activation of histamine H(1)- and/or alpha-adrenergic receptors, interference with calcium channels and/or stimulation of prostaglandin synthesis in utero.

Hypoglycemic activity of aqueous seed extract of Hunteria umbellata in normal and streptozotocin-induced diabetic rats.

The present study evaluated the aqueous seed extract of Hunteria umbellata K. Schum (Apocynaceae) for hypoglycemic activity in rats. Diabetes was induced by a single dose of streptozotocin (50 mg/kg i.p.). Daily doses of 400, 800, and 1000 mg/kg of extract were orally administered to fasted normal and diabetic rats. Blood glucose levels were monitored after 0, 2, 4, 8, 12 h and on day 14 post treatment. Liver glycogen levels were also estimated on day 14. In normal rats, only 400 mg/kg of the extract produced a significant reduction in blood glucose at the 4 h (P < 0.05) which was 22.15 ± 4.88%. In diabetic rats, the extract, 400, 800 mg/kg, caused significant reduction (P < 0.01), 51.87% ± 5.79% and 43.47% ± 8.06% respectively, with maximum effect at 8 h. This reduction in blood glucose was greater than that of glibenclamide (31.03% ± 8.86%). Diabetic rats administered with 400 mg/kg extract produced a significant reduction (P < 0.01) on day 14 (43.60% ± 8.10%). Liver glycogen levels were significantly increased (P < 0.05) in diabetic rats administered with doses of 400 and 800 mg/kg extracts and these were comparable to glibenclamide. Acute toxicity data showed no mortality in mice up to 17.5 g/kg. We conclude that the extract possesses marked hypoglycemic effects in diabetic rats possibly through increased glycogenesis, thus justifying its use in herbal medicine for the treatment of diabetes.

Some Studies on the Rodenticidal Action of Indomethacin

The oral LD50 of indomethacin for a seven-day observation was found to be 12.58 +/- 1.15 mg/kg. At LD10 of 6.61 mg/kg, a dose to weight ratio of 28 was obtained for a 240 g rat, while at a maximum single dose of 3 mg/kg in man it is only 0.04. Neither diazepam nor phenobarbital influenced death at the doses of both drugs used. However, cholestyramine 2 g/kg/day was found to protect by 50% from the LD100 of indomethacin. Gross pathological studies showed dose-dependent ulceration and perforation (P < 0.001, 12 vs 24 mg/kg) and such lesions occurred in starved rats, were low in bile duct-ligated compared to sham-operated rats (P < 0.001) and were also low in cholestyramine-treated rats. Indomethacin-induced lethality in rats was found to be dose-dependent.

Evaluation of the potassium channel activator levcromakalim (BRL38227) on the lipid profile, electrolytes and blood glucose levels of streptozotocin‐diabetic rats (评估钾通道激活剂左克罗卡林（BRL38227）对链脲霉素‐糖尿病大鼠血脂谱、电解质以及血糖水平的影响)

Levcromakalim is a vasorelaxant used in the management of hypertension in diabetes mellitus. Thus, the effects of levcromakalim were investigated in streptozotocin (STZ)‐diabetic rats.

Efficacy of Initiating Therapy with Amlodipine and Hydrochlorothiazide or Their Combination in Hypertensive Nigerians

In order to evaluate whether amlodipine or hydrochlorothiazide would be preferable to initiate therapy, 90 untreated hypertensive Nigerians of both genders aged 31–86 years with blood pressure >160/90 and ≤180/120 mm Hg were recruited into a randomized 48-week study. Patients, 30 each in amlodipine, hydrochlorothiazide, and amlodipine–hydrochlorothiazide groups, were treated, respectively, with amlodipine 5 mg for 6 weeks and the dose increased to 10 mg till week 12, after which hydrochlorothiazide 25 mg was added; hydrochlorothiazide 25 mg till week 6, after which amlodipine 5–10 mg was added; and amlodipine 5–10 mg + hydrochlorothiazide 25 mg. Body mass index, blood pressure, heart rate, and 24-hour urine volume were evaluated at baseline and at the end of weeks 1, 3, 6, 12, 24, 36, and 48. The primary efficacy variables were decreased in mean trough sitting diastolic and systolic blood pressure such that blood pressure < 140/90 mm Hg was regarded as normalized. At week 48 in the amlodipine group, 27 patients versus 25 patients in the hydrochlorothiazide group had diastolic blood pressure <90 mm Hg (90% vs. 83.3%; P <.03). In the amlodipine group, 23 patients versus 20 patients in the hydrochlorothiazide group had blood pressure < 140/90 mm Hg (76.7% vs. 66.7%; P <.01). In the amlodipine–hydrochlorothiazide group, 27 patients (90%) and 15 patients (50%) had diastolic blood pressure <90 mm Hg and blood pressure < 140/90 mm Hg, respectively. This study has demonstrated that a regimen of amlodipine to which hydrochlorothiazide is subsequently added provides superior efficacy on blood pressure control when compared with a regimen of hydrochlorothiazide to which amlodipine is subsequently added or with ab initio amlodipine–hydrochlorothiazide combination therapy.

Antiinflammatory Activity of Aqueous Extract of Stereospermum kunthianum (Cham, Sandrine Petit) Stem Bark in Rats.

Stereospermum kunthianum, Cham, Sandrine Petit (family: Bignoniaceae) is used in traditional medicine to treat bronchitis, pneumonia and coughs, gastritis, wounds, rheumatic arthritis, ulcers, dysentery, leprosy and venereal diseases in humans. The antiinflammatory activity of the aqueous extract of the stem bark was investigated with experimental animal models using the carrageenan-induced paw oedema, leucocytes migration and granuloma air pouch tests in rats. The extract (100, 200 or 400 mg/kg) at 3 h post-treatment caused a significant (p<0.05) reduction in the paw oedema in rats. The effect of the extract was most pronounced at the dose of 400 mg/kg and was higher than that of indomethacin (10 mg/kg). The extract (400 mg/kg) caused a significant (p<0.05) reduction in the number of recruited leucocytes and its inhibition of peritoneal exudate formation was comparable to that of indomethacin at a dose of 10 mg/kg. The exudate formation inhibited by 400 mg/kg of the extract in the granuloma air pouch test was comparatively less to that of indomethacin at a dose of 10 mg/kg. The findings of the study indicate that the aqueous extract of Stereospermum kunthianum stem bark possesses antiinflammatory activity which is probably related to the inhibition of prostaglandin synthesis. This is a possible rationale for its folkloric use as an antiinflammatory agent.

Increased superoxide dismutase and Na+, K+-ATPase activities in aortic strips from potassium-adapted rats: implication for altered vascular reactivity

The contributions of superoxide dismutase (SOD) and Na(+), K(+)-ATPase to the altered vascular reactivity in potassium-adapted rats were investigated to test the hypothesis that smooth muscle hyperpolarisation may be involved. Isometric contractions to noradrenaline (NA), 5-hydroxytryptamine (5-HT), and relaxations to acetylcholine (ACh), levcromakalim (LEV) and sodium nitroprusside (SNP), were measured in aortic rings from potassium-adapted rats. Pieces of the aortae were also excised from the animals and assayed for SOD and Na(+), K(+)-ATPase. Maximum contractile responses were significantly attenuated (P<0.05) in aortic rings from the potassium-adapted rats to NA and 5-HT, while relaxations were also significantly augmented (P<0.05) in the same rings to LEV and SNP, but not to ACh. Both SOD and Na(+), K(+)-ATPase activities were significantly higher (P<0.05) in the aortae from the potassium-adapted rats compared to controls. It is concluded that the alteration in vascular smooth muscle reactivity may be due to hyperpolarisation caused by the activities of SOD and Na(+), K(+)-ATPase.

Haematological influences of potassium adaptation in normotensive and renally-hypertensive Wistar rats.

Abstract Dietary potassium is known to cause reduction in blood pressure in several models of hypertension in human and animal studies but its haematological effects are not known. Here, experiments are designed to study the haematological effects of potassium adaptation (achieved by administering 0.75% KCl solution in drinking water for five weeks) in Wistar rats. The animals are divided into four groups comprising controls, potassium-adapted, renal hypertensive, and renal hypertensive with later adaptation to potassium. Packed cell volume (PCV) and platelet count (PC), whole blood and plasma viscosities, and platelet aggregation in the presence of sodium nitroprusside, levcromakalim, and glibenclamide, are studied. Results showed comparable PCV and PC in all groups. While relative whole blood viscosity was significantly higher (P<0.05) in the hypertensive group, relative plasma viscosity was similar in all groups. Adaptation significantly reduced (P<0.05) the tendency of platelets to aggregate to collagen. Sodium nitroprusside significantly reduced (P<0.05) the pro-aggregatory effects of collagen only in the control group. Neither of the potassium-channel modulators (levcromakalim, glibenclamide) caused any significant alteration in platelet response to collagen at the concentrations studied. Although these results suggest that potassium adaptation may not affect haemorheology, the reduced ability of platelets to aggregate – by mechanisms not clearly understood – has implications for reduced thromboembolism and the attendant cardiovascular sequelae.