Vitamin D supplementation improves insulin resistance in type 2 diabetes subjects in Lagos, Nigeria

Type 2 diabetes is a disease caused by both insulin resistance and an insulin secretory defect. Reports suggest that vitamin D3 supplementation improves insulin resistance and pancreatic beta-cell function, but there is paucity of data on vitamin D and glycaemia in type 2 diabetes in Nigeria. We have therefore performed a single blind prospective randomised placebo-controlled trial, involving type 2 diabetes participants in Lagos, Nigeria. The participants consisted of 42 type 2 diabetes patients with vitamin D deficiency. These participants were randomised into two equal groups of treatment and a placebo arm. Vitamin D3(3000 IU daily) was given to the participants in the treatment arm. Insulin resistance (HOMA-IR) and pancreatic beta-cell (HOMA-B) function were determined at baseline and after 12 weeks of vitamin D3 supplementation, or placebo treatment. There was a reduction from baseline in the mean insulin resistance level in both the treatment and placebo groups. How-ever, this reduction was only statistically significant in the treatment group (p <0.01). The proportion of subjects with improvement in insulin resistance status (homeostatic model assessment insulin resistance score (HOMA-IR)<2.0) was significantly higher in the treatment arm (p<0.05). There was a reduction in the mean insulin secretory capacity in the treatment group while it increased in the placebo group, though this difference was not statistically significant. We conclude that vitamin D3 supplementation results in a reduction in insulin resistance, but has no effect on pancreatic beta-cell function in type 2 diabetes

α-Glucosidase Inhibitory Prenylated Anthranols from Harungana madagascariensis.

Four new prenylated anthranols, harunganols C-F (1-4), along with kenganthranol A (5), harunganin (6), and ferruginin A (7), were identified from the leaves of Harungana madagascariensis. The structures of compounds 2, 5, and 7 were confirmed by single-crystal X-ray diffraction analysis. Compound 1 is a unique symmetrical anthranol dimer connected via a CH2 group. Compound 4 possesses a unique C-10 hemiketal group. All anthranols were evaluated for their α-glucosidase inhibitory activities. They displayed a higher potency compared to acarbose except for 3 and 4. In particular, harunganol C (1) showed an IC50 value of 1.2 µM.

Anti-cancerous triterpenoid saponins from Lecaniodiscus cupanioides.

From the ethanol extract of the stem of Lecaniodiscus cupanioides Planch, two known compounds 1 and 2 were isolated and identified as triterpenoid saponins 3-O-[α-L-arabinofuranosyl- (1→3)-α-L-rhamnopyranosyl- (1→2)-α-L-arabinopyranosyl-]-hederagenin and 3-O- [α-L-arabinopyranosyl- (1→3)-α-L-rhamnopyranosyl (1→2)-α-L-arabinopyranosyl-]-hederagenin. The structures were established by physicochemical and spectroscopic investigations (MS and NMR) as well as comparison of literature data. The compound 1 exhibited anticancer activity against human colon carcinoma H-116, human lung carcinoma A-549 and human lung carcinoma HT-29 cell lines with IC50 5.0, 2.5 and 2.5µg/ml respectively and compound 2 exhibited similar activities with IC505.0, 5.0 and 2.5µg/ml respectively. This suggests that the isolated triterpenoid saponins may be considered as potential anticancer leads for further studies.

Traditional medicinal plants in Nigeria--remedies or risks.

ETHNO-PHARMACOLOGICAL RELEVANCE: Soil pollution due to increasing industrialization is a reality that is taking its toll on mankind today. Considering the population of people that use herbal remedies especially in developing countries and the discharge of industrial waste on surrounding herbal vegetation, it is imperative to determine the heavy metals contamination in some commonly used medicinal plants. MATERIALS AND METHODS: Representative samples of five medicinal plants Ageratum conyzoides, Aspilia africana, Alchornea cordifolia, Amaranthus brasiliensis and Chromolaena odorata were collected from Ikpoba-Okha L.G.A, Edo State Nigeria, around a paint company and another set of same plants were collected from a non-polluted source. Dried leaves and roots of collected plants were digested and analyzed using Atomic Absorption Spectrophotometer (AAS) for the presence of Lead (Pb), Cadmium (Cd), Chromium (Cr), Nickel (Ni) and Zinc (Zn). Soil samples from polluted and non-polluted areas were also analyzed to ascertain the levels of these heavy metals in the environment. RESULTS: Results show that the concentrations of these heavy metals in the leaves and roots of plants collected from polluted soil were significantly higher than those obtained from unpolluted soil. Correspondingly heavy metal concentrations were significantly higher in polluted than in unpolluted soil samples. CONCLUSION: As part of continuing effort in the standardization of traditional remedies, environmental contamination control and abatement is evident. The source of medicinal plants/herbs should also be a cause for concern since the toxicity of medicinal plants is sometimes associated with environmental sources of the plants.

Evaluation of antioxidant activity of Tetracarpidium conophorum (Müll. Arg) Hutch & Dalziel leaves.

This study evaluated the antioxidant activity as well as bioflavonoid content of the methanol and ethanol-water extracts of the fresh and dried leaves of Tetracarpidium conophorum. Antioxidant activity was determined by spectrophotometric methods using DPPH free radical, nitric oxide radical inhibition and ferric reducing antioxidant power assays. In addition, total phenolics, flavonoids and proanthocyanidin content were also determined. The ethanol: water extract of the dried leaves had the highest antioxidant activity with a 50% inhibition of DPPH at a concentration of 0.017 mg/mL compared to the standards, Vitamin C and Vitamin E with inhibition of 0.019 and 0.011 mg/mL, respectively. This extract also showed nitric oxide radical inhibition activity comparable to that of rutin, 54.45% and 55.03% for extract and rutin, respectively, at 0.1 mg/mL. Ferric reducing power was also comparable to that of ascorbic acid (281 and 287 µM Fe (11)/g, resp.) at a concentration of 1 mg/mL. The methanol extract of both the dried and the fresh leaves had higher phenolic, flavonoids and proanthocyanidin content than the ethanol:water extract. The study reveals that T. conophorum can be an interesting source of antioxidants with their potential use in different fields namely food, cosmetics and pharmaceuticals.

Pesticide residue levels in maize samples from markets in Lagos State, Nigeria.

BACKGROUND: Pesticides are used widely in agriculture to control destructive pests and hence increase food supply. Their use inadvertently leads to residues in food crops and the environment. Pesticides, by nature are poisonous and exposure of humans to their residues may cause health hazards which include neurotoxicity and carcinogenicity among others. Evaluation of pesticide residues in food is therefore of public health importance and would help to ensure that levels are kept within safety limits. OBJECTIVE: The aim of this study was to determine the incidence and quantity of organochlorine pesticide residues in maize samples collected from various markets in Lagos State and compare values obtained with established safety values in order to highlight possible health hazards. METHODS: In this study, samples of white maize (Zea mays L.) purchased from different markets in Lagos State were analyzed for residues of organochlorine pesticides using gas chromatograph with mass spectrometric detector (GC-MS) after careful extraction and cleanup. RESULTS: The results showed that 96% of the maize samples contained residues of one or more organochlorine pesticides. Mean concentrations ranged from 7.9-52.0 microg/kg and maximum residue limits (MRLs) of some pesticides were exceeded in up to 7% of samples. The estimated total diet intakes (ETDIs) for aldrin and dieldrin exceeded their maximum permissible intakes. CONCLUSION: It is concluded that residues of organochlorine pesticides are present in maize in Lagos markets. Some exceed safety levels with possible adverse effects on human health. There is therefore a need for more stringent monitoring of the use of pesticides in agriculture and food storage in Nigeria.

Comparative dissolution profiles of representative quinolones in different media.

BACKGROUND: Quinolones have a broad spectrum of activity against bacteria and are a class of synthetic antimicrobial modeled after nalidixic acid. OBJECTIVE: To determine the dissolution efficiencies of ciprofloxacin and sparfloxacin in 0.1NHCL, deionized water, 0.1 M acetic acid and pH 7.4 phosphate buffer. METHODS: The in-vitro dissolution profiles of ciprofloxacin (250 mg and 500 mg) and sparfloxacin (200 mg) tablets were studied in the respective media using US Pharmacopoeia (USP) Apparatus II. In order to monitor the comparative rate of dissolution, samples were withdrawn from the medium for quantification over nine pre-determined time points during a total period of two hours. Samples were analyzed by an HPLC method capable of concurrent elution of ciprofloxacin/sparfloxacin. RESULTS: The medium with most stable release pattern for the representative quinolones was 0.1M acetic acid, followed by 0.1NHCl, distilled water and pH 7.4 buffer respectively. The %Q30 of Ciprofloxacin(CP) and Sparfloxacin(SP) was found to conform entirely to both USP2004 and FDA specifications. Sparfloxacin was found to be unstable due to cloudiness observed in 0.1N HCl medium. The CP and SP showed highest %Q(max) in 0.1M acetic acid compared to other media. This result has implication in the choice of medium for dissolution testing of quinolones, particularly for comparative purposes in the absence of specific monograph recommendations. Furthermore, it supports the change from 0.1N to 0.01NHCI for ciprofloxacin in the USP as a monographic modification. CONCLUSION: We conclude that there is a need to have a general-purpose dissolution medium for comparing profiles of different quinolones, 0.1M acetic acid may be a suitable candidate. Furthermore, the study may serve as guidance to the drug regulatory authorities in formulation of monographs for the drugs.

Evaluation of Antioxidant Properties of Phaulopsis fascisepala C.B.Cl. (Acanthaceae).

The antioxidant activities of crude extract of Phaulopsis fascisepala leaf were evaluated and compared with alpha-tocopherol and BHT as synthetic antioxidants and ascorbic acid as natural-based antioxidant. In vitro, we studied its antioxidative activities, radical-scavenging effects, Fe(2+)-chelating ability and reducing power. The total phenolic content was determined and expressed in gallic acid equivalent. The extract showed variable activities in all of these in vitro tests. The antioxidant effect of P. fascisepala was strongly dose dependent, increased with increasing leaf extract dose and then leveled off with further increase in extract dose. Compared to other antioxidants used in the study, alpha-Tocopherol, ascorbic acid and BHT, P. fascisepala leaf extract showed less scavenging effect on alpha,alpha,-diphenyl-beta-picrylhydrazyl (DPPH) radical and less reducing power on Fe(3+)/ferricyanide complex but better Fe(2+)-chelating ability. These results revealed the in vitro antioxidant activity of P. fascisepala. Further investigations are necessary to verify these activities in vivo.

Artesunate causes relaxation of rat aortic rings and reduces the contractile response to noradrenaline.

OBJECTIVE: To study if the present widely used artemisin derived anti-malaria drugs have vascular effects. METHODS: Aortic rings were obtained from adult male Sprague-Dawley rats. The rings were mounted in an organ bath and tension recorded using isometric force transducers. After pre-contraction with noradrenaline, cumulative doses of artesunate were added to the bath containing the rings. The effects of nitric oxide inhibition with L-NAME, on the responses to artesunate were also assessed. Lastly the effects on the contractile responses of the rings to noradrenaline (NA) were determined before and after incubation in artesunate. RESULTS: Cumulative addition of artesunate from 6 x 10(-4) to 6 x 10(-1) mg/ml resulted in relaxation of pre-contracted aortic rings. L-NAME significantly reduced the relaxation response to artesunate (P < 0.05). Vascular contraction response to NA was significantly reduced (P < 0.01) following the addition of artesunate. CONCLUSION: Artesunate causes relaxation of precontracted rat aortic rings which is partly mediated by Nitric Oxide (EDRF). It also reduces the contractile responses of the rings to noradrenaline.

The physicochemical and antibacterial properties of ciprofloxacin-Mg2+ complex.

PURPOSE: Co-administration of quinolone antibiotics with cation-containing medicaments such as, antacids has been reported to influence the overall bioavailability leading to subtherapeutic plasma concentrations of these antibiotics in humans. OBJECTIVES OF THE STUDY: The present work was designed to evaluate the binding constant, binding molar ratio, influence of temperature on the binding constant of ciprofloxacin-Mg2+ and to determine the antimicrobial activity of ciprofloxacin and ciprofloxacin-Mg2+. METHODS: Job's method of continuous variation and Bonesi-Hildebrand equation were adopted to determine the molar ratio and stability constant respectively. The antibacterial activity was determined by the Agar diffusion method. RESULTS: A complexation molar ratio of 1:1 was obtained for ciprofloxacin-Mg2+ complex. The stability constants were 3.59 and 3.50 at 25 degrees C and 60 degrees C respectively. There was a significant difference between the zones of inhibition of ciprofloxacin-Mg2+ complex and that of ciprofloxacin alone against E. coli, P. aeruginosa, and S. aureus (p < 0.05). This difference showed that the complex formed was not as active as ciprofloxacin. CONCLUSION: The present studies have shown that ciprofloxacin readily complex with Mg2+ and that the stability constant was temperature dependent. The antibacterial activity of ciprofloxacin was markedly reduced in the presence of Mg2+. Concomitant administration of ciprofloxacin with Mg2. containing medicaments should be avoided to prevent resistance.

Invitro evaluation of the neutralising capacity of twenty brands of antacids in Lagos, Nigeria.

BACKGROUND: The use of substandard drugs is a great threat to the lives of people in the community. Identification of substandard drugs is important to exclude their use in clinical practice. These drugs may lead to reduced efficacy of pharmacotherapy. Antacid preparations are weakly basic and consist of metal salts, most commonly aluminium hydroxide or magnesium hydroxide. These salts dissociate to neutralise gastric acid and form neutral salts. The ultimate goal of antacid therapy is to reduce the concentration and the total load of acid in gastric juice with a pH of 1.3 to a pH between 3.5 and 5.0. OBJECTIVE: The aim of this work is to carry out an in-vitro test on the acid neutralising capacity (ANC) of commonly available antacid brands in Lagos market. METHOD: The British pharmacopoeia (BP) method of analysis of antacids was adopted. Twenty different brands of antacid suspensions and tablets were analysed. RESULT: Brand SH suspension gave the highest neutralising capacity, 101.65 ml +/- 0.15, while brand SN gave the lowest, 99.75 ml +/- 0.75. All the fourteen antacid suspensions analysed complied with the official specification and therefore passed the analysis. Brand TB tablet gave the highest acid neutralising capacity (ANC), 54.10 ml +/- 0.2 while brand TD 49.50 ml +/- 0.1 gave the lowest. All the six antacid tablet brands analysed passed the assay. The ANC of an antacid is a parameter used to measure the effectiveness of an antacid in relieving ulcer pain. CONCLUSION: The acid-neutralising capacity of the antacid brands analysed were within the BP specification. The acid neutralising capacity of antacids should be determined before administration.

Antioxidant activities of methanolic extract of Sapium ellipticum.

The stem bark extract of S. ellipticum (Hochst) Pax was investigated for its antioxidant properties in this study. The extract was evaluated for antioxidant activity in vitro in terms of its ability to inhibit lipid peroxidation and its free radical scavenging, reducing and metal chelation powers. The total amount of phenolic compounds in the extract was also determined in terms of gallic acid equivalent. The extract produced effective free radical scavenging and reducing activities in a dose dependent fashion. The extract exhibited noticeable inhibition of lipid peroxidation of linoleic acid emulsion. These activities were less than that of ascorbic acid and 2,6-Di-tert-butyl-4-methylphenol used as positive controls. The extract however demonstrated poor iron chelating ability compared to ethylene diamine tetraacetic acid. The total phenolic content of the extract was 50.61 +/- 0.08 mg g(-1) in terms of gallic acid. This study showed that the stem bark extract of S. ellipticum exhibits significant antioxidant activity and is a good source of natural antioxidants.

Phytochemical Screening and Free Radical Scavenging Activities of the Fruits and Leaves of Allanblackia floribunda Oliv (Guttiferae)

Purpose: To compare the phytochemical constituents in the leaves and fruits of Allanblackia floribunda and determine their free radical scavenging activity. Methods: The fruit and leaves of AF collected from the uncultivated farmlands of Okeigbo; Ondo State; Nigeria; were dried; milled and extracted with methanol. Phytochemical screening was carried out according to standard procedures. Free radical scavenging activity was determined by measuring the decrease in the visible absorbance of 2;2-diphenyl-1-picrylhydrazyl (DPPH) on addition of the plant extract. The mean inhibitory concentration (IC50); which is the concentration of extract needed to decrease the initial absorbance of DPPH by 50was determined graphically. Total phenolic; flavonoids and proanthocyanidin contents were determined by spectro-photometric methods. Results: Alkaloids; anthraquinones; tannins; saponins; steroids; terpenoids; flavonoids and cardiac glycosides were found to be present in both the fruits and leaves. Only AF fruit contained phlobatannins. IC50 values of 0.01; 0.02 and 0.1 mg/ml were recorded for Vitamin E; AF leaves and AF fruits respectively. Total phenolic; total flavonoid and proanthocyanidin contents were 65; 0.07 and 2.38 mg/g of powdered plant material for AF fruits; and 12; 51.35; 19.5 mg/g of powdered plant material for AF leaves as gallic acid; rutin and catechin equivalents respectively. Conclusion: AF leaves are five times more potent as a free radical scavenger compared to the fruits though the fruit was found to contain a higher phenolic content

Phytochemical Screening and Free Radical Scavenging Activities of the Fruits and Leaves of Allanblackia floribunda Oliv (Guttiferae)

Purpose: To compare the phytochemical constituents in the leaves and fruits of Allanblackia floribunda and determine their free radical scavenging activity. Methods: The fruit and leaves of AF collected from the uncultivated farmlands of Okeigbo; Ondo State; Nigeria; were dried; milled and extracted with methanol. Phytochemical screening was carried out according to standard procedures. Free radical scavenging activity was determined by measuring the decrease in the visible absorbance of 2;2-diphenyl-1 -picrylhydrazyl (DPPH) on addition of the plant extract. The mean inhibitory concentration (IC50); which is the concentration of extract needed to decrease the initial absorbance of DPPH by 50was determined graphically. Total phenolic; flavonoids and proanthocyanidin contents were determined by spectro-photometric methods. Results: Alkaloids; anthraquinones; tannins; saponins; steroids; terpenoids; flavonoids and cardiac glycosides were found to be present in both the fruits and leaves. Only AF fruit contained phlobatannins. IC50 values of 0.01; 0.02 and 0.1 mg/ml were recorded for Vitamin E; AF leaves and AF fruits respectively. Total phenolic; total flavonoid and proanthocyanidin contents were 65; 0.07 and 2.38 mg/g of powdered plant material for AF fruits; and 12; 51.35; 19.5 mg/g of powdered plant material for AF leaves as gallic acid; rutin and catechin equivalents respectively. Conclusion: AF leaves are five times more potent as a free radical scavenger compared to the fruits though the fruit was found to contain a higher phenolic content

Phytochemical Screening and Antioxidant Activities of some Selected Medicinal Plants Used for Malaria Therapy in Southwestern Nigeria

Purpose: Oxidative stress has been shown to play an important role in the development of anaemia in malaria. Indeed; increase in total antioxidant status has been shown to be important in recovery from malaria. The antioxidant activities of four medicinal plants traditionally used in the treatment of malaria in southwestern Nigeria were determi- ned. Methods: The ethanolic extracts of the leaves of Carica papaya Linn. [Caricaceae] ; stem bark of Magnifera indica Linn. [Anacardiaceae]; leaves of Psidium guajava Linn. [Myrtaceae] and the leaves of Vernonia amygdalina Del. [Compositae]; were used in the present study. The plant parts commonly used in the locality in malaria therapy were employed in this study. The plants were screened for the presence of phytochemicals and; their effect on 2;2-Diphenyl-1-picryl-hydrazyl radical (DPPH) was used to determine their free radical scavenging activity. Results: Phytochemical screening of the plants showed the presence of flavonoids; terpenoids; saponins; tannins and reducing sugars. M. indica did not contain cardiac glycosides and alkaloids while; P. guajava also showed the absence of alkaloids and anthraquinones. Anthraquinones was similarly absent from V. amygdalina. Concentrations of the plant extracts required for 50inhibition of DPPH radical scavenging effect (IC50) were recorded as 0.04 mg/ml; 0.313 mg/ml; 0.58 mg/ml; 2.30 mg/ml and 0.054 mg/ml for P. guajava; M. Indica; C. papaya; V. amygdalina and Vitamin C; respectively. Conclusion : All the plants showed potent inhibition of DPPH radical scavenging activity; P. guajava being the most potent. The free radical scavenging (antioxidant) activities of these plants probably contribute to the effectiveness of the above plants in malaria therapy

Effect of Five Alive fruit juice on the dissolution and absorption profiles of ciprofloxacin.

OBJECTIVE: To determine the effect of interaction of five Alive fruit juice on the dissolution and absorption profiles of ciprofloxacin tablets using urinary excretion. METHODS: In-vitro dissolution of ciprofloxacin 500 mg tablets was studied using US Pharmacopoeia dissolution apparatus II. This was conducted using 0.1N HCl and equal volumes of the fruit juice and 0.1N HCL. Samples were collected at predetermined time intervals for two hours. For the in-vivo study, eleven (5 males and 6 females) healthy volunteers participated in an open, single dose, cross-over randomized trial. After an overnight fasting, each volunteer either ingested a 500 mg ciprofloxacin tablet with 250 ml table water or with the fruit juice. Total urine voided was collected for 72 hrs after each dose of ciprofloxacin. Dissolution and urine samples were assayed using a controlled and validated UV spectrophotometric analysis. RESULTS: A lag time of 5 minutes was observed in dissolution profile of ciprofloxacin in the juice. The percent dissolved of ciprofloxacin in 0.1NHCl and fruit juice were found to be dissimilar (f2 =18.2) using similarity factor. There was statistical difference between the K(el) (elimination constant), K(e) (excretion rate) and X(u) (cumulative amount excreted unchanged) of subjects on water (0.1759 +/- 0.0144; 12.81 +/- 1.36; 375.5 +/- 41.2) and that of fruit juice (0.1250 +/- 0.0161; 7.6 +/- 1.07; 241.6 +/- 34.0). However, there was no difference between the t(1/2) of the subjects (4.2 +/- 0.3; 5.5 +/- 0.8). There was a decrease in relative availability of the drug by 35.75%. CONCLUSION: We conclude that the absorption of ciprofloxacin can be reduced by concomitant ingestion of the juice containing calcium carbonate and grape. Therefore to avoid drug therapeutic failures and subsequent bacterial resistance as a result of subtherapeutic level of the drug in the systemic circulation, ingestion of the juice with ciprofloxacin should be discouraged.

Bioavailability of ciprofloxacin and fleroxacin: results of a preliminary investigation in healthy adult Nigerian male volunteers.

The absolute bioavailability (BA) of ciprofloxacin and fleroxacin were evaluated in 19 adult Nigerian male volunteers. Subjects meeting the selection criteria were randomized to receive treatment either with fleroxacin (200 mg-i.v. and 200 mg oral dose) or ciprofloxacin (200 mg-i.v. and 250 mg oral dose). The i.v./oral or oral/i.v. switch was made after a one week washout period. Blood and urine samples were collected at pre-determined time intervals over a 72 h period for analysis of drug levels. Following intravenous administration the maximum serum concentration (Cmax) was 2.7+/-1.06mg/l for ciprofioxacin and 0.99+/-0.41 mg/l for fleroxacin; the area under the blood level curve (AUC) was 8.82+/-3.19 mg x h/l with ciprofloxacin and 8.52+/-3.83 mg x h/l with fleroxacin. Following oral administration the Cmax was 1.52+/-0.94 mg/l with ciprofloxacin and 0.57+/-0.08 mg/l with fleroxacin; the AUC was 9.87+/-4.10 and 7.55+/-1.42 mg x h/l, respectively. The absolute BA following oral administration was found to be 0.79+/-0.47 for ciprofloxacin and 1.01+/-0.78 for fleroxacin. When these BA results were corrected for renal clearance [Cl(r)] and elimination half-life (t1/2) the values were reduced to 0.37+/-0.17 and 0.31+/-0.18, respectively, for ciprofloxacin and 0.53+/-0.23 and 0.99+/-0.38, respectively, for fleroxacin. Only 38% with ciprofloxacin and 59% with fieroxacin, of the administered dose, was excreted unchanged following oral administration. More work, however, needs to be done on ciprofloxacin to support and/or confirm the above findings. Fleroxacin, on the one hand, exhibited a different trend from that observed in the literature with respect to Cmax and AUC where the values observed in this study were 3--4 fold lower than expected following identical doses, whilst on the other hand the observed BA profile in this study was consistent with literature trends.