Showing papers in "African Journal of Pharmacy and Pharmacology in 2016"

A review of twenty ethnobotanicals used in the management of breast cancer in Abeokuta, Ogun State, Nigeria

Abstract: Ethnobotanical investigation revealed the use of Alafia barteri Oliv., Allium ascalonicum L., Alstonia congensis Engl., Anthocleista djalonensis A. Chev., Calliandra portoricensis (Jacq.) Benth., Capsicum frutescens L., Clausena anisata (Willd.) Hook f. ex Benth., Erythophleum suaveolens (Guill. & Perr.) Brenan, Grewia flavescens Juss., Khaya ivorensis A. Chev., Kigelia africana (Lam.) Benth., Lophira alata Banks ex C.F. Gaertn., Macaranga barteri Mull. Arg., Olax subscorpoioidea Oliv., Plumbago zeylanica L., Tephrosia vogelli L., Tetracera alnifolia Willd., Tetrapleura tetraptera (Schum. & Thonn.) Taub., Triclisia subcordata Oliv., and Xylopia aethiopica (Dunal.) A. Rich. in the management of breast cancer in Ogun State, Nigeria. The prevalence of breast cancer in Nigeria was 15.3 per 100,000 in 1976 and 33.6 per 100,000 in 1992. Breast cancer is the leading malignancy in the South Western Nigeria; it is second to cancer of the cervix in the north-west. In north-central, 22.41% of new cancer was registered for breast cancer in five years and accounted for 35.41% of all cancers in women. The limitations of orthodox drugs such as cost, accessibility, effectiveness, and side effects necessitate the search for cheap, safe and effective phytomedicine in cancer management. Thus, this paper reviewed twenty plants used traditionally for the management of breast cancer; this was with a view to presenting them for future research activities and scientific validation of their potency in cancer regimen. Key words: Ethnobotanicals, breast cancer, traditional recipes, Ogun State, Nigeria.

Antioxidant properties of antiepileptic drugs levetiracetam and clonazepam in mice brain after in vitro-induced oxidative stress

Abstract: This study aimed to investigate the in vitro antioxidant activity of the novel anticonvulsant levetiracetam and benzodiazepine clonazepam. To do this, the mice brain homogenates were incubated with levetiracetam (50, 100 or 200 i­g/ml) or clonazepam (50, 100 or 200 i­g/ml), and then, submitted to heating at 37°C for 1 h. Ascorbic acid (vitamin C, 200 i­g/ml) was used as reference antioxidant drug. The markers of oxidative stress, such as lipid peroxidation, nitrite-nitrate content, catalase activity, and reduced glutathione (GSH) levels, were measured in brain homogenates. The group submitted to the heating-induced oxidative stress showed an increase in lipid peroxidation, nitrite-nitrate content, and catalase activity. Previous incubation with levetiracetam and clonazepam, mainly at lower doses (50 and 100 i­g/ml), and similarly to vitamin C, prevented these pro-oxidative changes, reducing the lipid peroxidation, nitrite-nitrate contents and catalase activity, and increasing GSH levels. These findings demonstrate antioxidant properties of levetiracetam and clonazepam, and help to elucidate the role of protection against oxidative stress in the neuroprotective mechanism of antiepileptic drugs. Key words: Levetiracetam, clonazepam, oxidative stress, vitamin C, antiepileptic drugs.

Acute toxicity and hypoglycaemic activity of the leaf extracts of Persea americana Mill. (Lauraceae) in Wistar rats

Abstract: Persea americana Mill. or avocado plant tree is well-known to people from the sub-Saharan part of Africa. Studies carried out earlier reported on the use of leaf extracts of the named plant to cure diabetes and other diseases in the south of Cote d’Ivoire. This study aimed to assess both acute toxicity and hypoglyceamic activity together with performing a comparative study. The acute toxicity was determined using the OECD 423 protocol, followed by the analysis of biochemical indicators, body weight variation and vital organs damage of healthy Wistar rats. The aqueous, ethanol and methanol extracts’ hypoglycaemic properties were investigated through the hypoglycaemic activity and oral glucose tolerance test. Thereafter, the phytochemical identification of the molecular compounds’ was carried out as well as polyphenols and total flavonoids quantification using Folin-ciacalteu and Neu reagent. The data analysis showed that P. americana leaf extracts’ are well tolerated in general at a unique dose of 2000 mg/kg. Nevertheless, a slight hepatitis occurrence was observed. Additionally, all extracts exhibited significant anti-hyperglyceamic activity 2 h after glucose administration. Ethanol extract (100 mg/kg) showed a strong activity by depleting the glyceamia rate by 59.6% during 5 h after glucose uptake as compared to glibenclamide at 61.6% followed by methanol extract at 49.2%. The ethanol extract also appeared to be the most provided with phenols and total flavonoids exhibiting respective amounts of 2952.7 ± 166 μg gallic acid equivalent/g and 0.582 ± 0.012%, respectively. The current study showed that both ethanol and methanol extracts displayed a good tolerance and significant anti-hyperglyceamic activity probably due to the presence of polyphenol in the extracts. Key words: Persea americana Mill., avocado, toxicity, glyceamia, diabetes, rat.

In vitro anthelmintic activity of Allium sativum, Allium cepa and Jatropha curcas against Toxocara canis and Ancylostoma caninum

Abstract: Prevalence of animal diseases is one of the major livestock production constraints in Kenya with high impacts on livelihoods due to related economic losses affecting food security in the country. The use of synthetic drugs for disease management has challenges. This makes the use of medicinal plants for treatment a rational alternative. Ascarids, Toxocara canis and Ancylostoma caninum are among the most frequently observed helminth parasites in dogs in Kenya. The two parasites are also known to cause helminthiasis in human beings. This study was designed to evaluate the in vitro efficacy of ethanol and aqueous extracts from bulbs of A. sativum and A. cepa and from leaves of J. curcas against T. canis and A. caninum parasites. Six (6) extracts from three (3) plants: A. cepa, A. sativum and J. curcas were selected for in vitro anthelmintic screening by measuring ability to inhibit hatching and development of eggs and survival of larvae in vitro. The ethanol extracts of A. cepa inhibited hatching of 100% of eggs of A. caninum between 10,000 and 2,500 ug/ml and 100% of eggs of T. canis between 10,000 and 1,250 ug/ml while that of A. sativum inhibited hatching of 100% of A. caninum eggs between 10,000 and 5,000 ug/ml. However the ethanol extract of A. sativum did not have the same effect on the development of T. canis eggs at these concentrations. The ethanol extracts of both A. cepa and A. sativum affected the survival of 100% of A. caninum larvae at a concentration of 156 ug/ml and above. The water extracts of the three plants had moderate effects on the eggs and the larvae of both parasites. The results indicate that the ethanol extracts of A. cepa and A. sativum have anthelmintic properties which should be investigated further to support the ethnoveterinary use of the plants as anthelmintics for control and treatment of worm infestation in dogs. Key words: Allium cepa, Allium sativum, Anthelmintic activity, Ancylostoma caninum, Jatropha curcas Toxocara canis.

Experimental evaluation of wound healing activity of Croton macrostachyus in rat

Abstract: Croton macrostachyus leaves are used for treatment of wounds by traditional healers in Ethiopia. Despite the use of this plant in the treatment of wound, there is limited data to support its medicinal use. The present study provides scientific evaluation for the wound healing potential of methanolic extract of C. macrostachyus leaves in rats. The leaves of Croton macrostachyus were studied for the presence of some secondary metabolites and wound healing activity. Ointments were made by incorporating the methanolic extract in simple ointment base B.P. in the concentration of 5 and 10% (w/w). Standard Nitrofurazone was used for comparison. Wound healing activity was studied, using excision and incision wound models. In excision wound model, percentage wound contraction, period of epithelization and morphological changes on the healed wounds were studied while incision wound model was used to determine breaking strength. The results were expressed as mean ± standard error of mean (SEM) and comparisons among treatment groups were made using one-way analysis of variance. Phytochemical screening of the methanolic extracts of leaves of C. macrostachyus showed the presence of different metabolites such as flavonoids and saponins which are reported to have significant wound healing activity. The results of epithelization period, percentage of wound contraction and morphological evaluation of groups of animals in the test groups showed significant (p < 0.05) wound healing activity compared to those treated with simple ointment. Similarly, the difference in breaking strength was significant (p < 0.05) for both 5 and 10% (w/w) methanol extract of C. macrostachyus ointment treated groups. Morphological evaluation showed a relatively better healing and growth of hair around the wound area in the 10% methanol extract of C. macrostachyus ointment treated group. Methanolic extract of C. macrostachyus enhanced wound healing significantly, corroborating the folk medicinal use of this plant. Key words: Croton macrostachyus, excision, incision, in vivo, wound healing.

DPPH radical scavenging and lipoxygenase inhibitory effects in extracts from Erythrina senegalensis (Fabaceae) DC

Abstract: Erythrina senegalensis DC (Fabaceae) is a plant used in traditional medicine in Burkina Faso (West Africa) to cure several diseases such as malaria, rheumatism, abdominal pain, fibroma and infections which are always accompanied by oxidative stress. This study aimed to highlight the antioxidant activities in dichloromethane (DCM) and ethyl acetate (EtOAc) extracts of E. senegalensis stem bark and roots. We used the 1, 1 diphenyl-2-picryl hydrazyl (DPPH) radical scavenging test and the 12-lipoxygenase I-B inhibitory method. We previously characterized the phytochemical groups by thin layer chromatography and colored reactions in tubes. The extracts in DCM (IC50-root: 5.18 ± 0.06 and IC50-bark: 5.76 ± 0.68) showed strong scavenging activity. However, as a 12-lipoxygenase inhibition, the DCM extracts were almost inactive. The EtOAc extracts from root (IC50-LOX: 7.21 ± 2.31; IC50-DPPH: 7.27 ± 0.13) and from stem bark (IC50-LOX : 4.95 ± 1.12; IC50-DPPH : 11.4 ± 1.3) presented both the radical scavenging and the 12-lipoxygenase inhibitory effects. Polyphenols (flavonoids, tannins), steroids and terpenoids characterized in all extracts may be involved in the observed 12-lipoxygenase inhibition and radical scavenging. Key words: E. senegalensis, antioxidant, 12-lipoxygenase I-B inhibitory.

Anticonvulsant and anxiolytic activity of the leaf aqueous and ethanolic extracts of Melanthera scandens in a rat model.

Abstract: Modern drug therapy of epilepsy is complicated by the inability of drugs to control seizures in some patients and side effects that range in severity from minimal impairment of the central nervous system to death from aplastic anemia or hepatic failure. Medicinal plants used in traditional medicine for the treatment of epilepsy have been scientifically shown to possess promising anticonvulsant activities in animal models for screening for anticonvulsant activity and can be a source of newer anticonvulsants. The aim of this study was to investigate the preliminary phytochemical properties, anticonvulsant and anxiolytic activities of Melanthera scandens aqueous and ethanolic extracts. Phytochemicals from the aqueous and ethanolic extracts were screened by standard methods. Anticonvulsant activity was evaluated against pentylenetetrazol (PTZ)-induced seizure model in rats. The effect of the extract at oral dose levels of 250, 500 and 1000 mg/kg was evaluated in an experimental rat model, using diazepam (5 mg/kg) as positive control. Anxiolytic activity was performed using elevated plus maze method. Phytochemical screening revealed that M. scandens extracts contain carbohydrates, flavonoids, saponins, glycosides, tannins, terpenoids, phenols and phytosterols. The aqueous extract at a dose of 500 mg/kg significantly increased seizure latency (P=0.0023), while the ethanolic extract did not have a significant effect on seizure latency. Both extracts significantly reduced the seizure severity (P= 0.0155), and provided up to 100% protection against PTZ induced death at 1000 mg/kg. Both extracts had no significant effect on the duration of PTZ induced seizures. Both extracts were found to increase the number of entries and the time spent in the open arms of the maze at a dose of 250 mg/kg, indicating anxiolytic activity, which was not seen at higher doses (500 and 1000 mg/kg). The total numbers of entries into the closed arm were significantly reduced at 500 and 1000 mg/kg oral doses of both extracts, indicating a reduction in locomotor activity of the rats. The results obtained in this study suggest that both the aqueous and ethanolic extracts of M. scandens possess anticonvulsant and anxiolytic activities in a rat model.

The effect of surfactant above and below the critical micelle concentration (CMC) and the mathematical models used to determine the kinetics of drug release from the matrix system

Abstract: The liberation of propranolol HCl from a controlled release matrix, containing the hydrophilic polymer, sodium carboxymethylcellulose (NaCMC) and the hydrophobic polymer, Eudragit RL 100 (RL 100) as excipients, was studied. The influences of surface active agents on the dissolution rate of the drug were examined. Tablets were made by direct compression methods. The dissolution tests were performed by using the basket method. The incorporation of the cationic surfactants within the matrices increased the drug release until the critical micelle concentration (CMC). While, after the CMC, the increase in drug release was to a lesser extent. The incorporation of the anionic surfactants reduced the release rate of the drug from the matrices. At the CMC, the percent of drug release from the matrices were approximately the same with the matrices without the surfactants. While an increase in drug release was observed above the CMC of the anionic surfactants. The data obtained from in vitro drug release studies were plotted according to three kinetic models to study the release kinetic. These were zero order release, the first order release and the Higuchi equation. Zero order release of the drug was observed in all the formulations. The release mechanism was influenced considerably by the ratio of the excipients. Key words: Propranolol HCl, controlled release, critical micelle concentration (CMC), dissolution, dissolution rate kinetics, surfactant.

Development of Pharmacy Education in Kenya Universities to date

Abstract: The purpose of this paper was to examine the development of pharmacy education in Kenya since independence. Websites of the Pharmacy and Poison Board of Kenya and the Commission for University Education as well as those of the universities offering pharmacy education were used to obtain information such as the framework for establishment of programmes in higher institutions, curriculum, regulation of pharmacy practice among others. From a single institution in the 1970s, six universities that are evenly divided between government and private ownerships now offer Bachelor of Pharmacy programs in Kenya. Irrespective of the ownership the requirement for the establishment of programs in Kenya universities is centrally formulated and established. Pharmacy education is regulated by both the Commission for University Education and Pharmacy and Poisons Board. Adequate and well trained, motivated and productive workforce is required for effective teaching and learning and thus the key elements for local and international competence of the graduates. The proliferation of pharmacy education institutions requires a greater and continuous collaboration amongst the regulators and the stakeholders to ensure that pharmacy graduates from these newly established schools are adequately trained and equipped to meet the ever changing healthcare needs of the populace. Key words: University, pharmacy education, healthcare, competence, human resource, Kenya.

Cytotoxicity, antifungal and antioxidant activities of the essential oil from Eupatorium ballotifolium Kunth (Asteraceae)

Abstract: This study aimed to characterize chemically and evaluate the cytotoxicity and antioxidant, antifungal and modulatory activities of the essential oil of Eupatorium ballotifolium, collected in the mountainous region of Meruoca in the state of Ceara. The antioxidant activity was investigated by the free radical 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging assay and β-carotene/linoleic-acid oxidation model system. The lethality bioassay was performed using Artemia salina (brine shrimp). The evaluation of the antifungal activity in vitro was performed by broth microdilution using strains of dermatophyte fungi and yeasts. The modulatory activity assays were performed by the checkerboard technique using ketoconazole as standard. Chromatographic analysis associated with mass spectrometry showed the main constituents of E. ballotifolium essential oil were β-caryophyllene (23.59%), thymol methyl ether (12.28%), germacrene D (6.56%) and bicyclogermacrene (6.47%). The brine shrimp lethality assay demonstrated potential biological activity. The essential oil showed better antioxidant action by the β-carotene/linoleic acid assay, with IC50 value of 19.47 µg/mL for essential oil, 11.32 µg/mL for thymol and 22.83 µg/mL for carvacrol, used as test standards. The broth microdilution test demonstrated that the essential oil inhibited fungal growth of all Trichophyton rubrum strains. In the modulation activity assay against strains of Trichophyton rubrum, there was synergism of essential oil on the strains of dermatophyte fungi when combined with ketoconazole. Key words: Compositae, Lourteigia ballotaefolia, Trichophyton rubrum, antioxidant activity, antimicrobial activity.

Use of zebrafish (Danio rerio) in experimental models for biological assay with natural products

Abstract: Research on natural products is facing significant difficulty. The analysis "high-throughput screening" has limited effectiveness in their evaluation. This report on in vitro screening of pharmacological activity of the drugs candidate molecule by evaluating a single target. The presence of many substances in a natural extract makes this process unprecise. The zebrafish (Danio rerio, ZF) is well suited to high-throughput applications owing to its high fecundity, rapid extrauterine development and transparency during organogenesis. This fact promotes increase in the relevance of their use in biological assays, which is hard to be matched in vitro. Tests based on ZF can aid in the isolation of bioactive molecules from plant extracts, which was identified in a large-scale screening. This increases the biological relevance of such findings. Another decisive factor for the use of ZF as an experimental model, for widespread testing, is the few extracts or the isolated compounds required for tests. Therefore, the growing number of publications and innovative models created for the research shows a lot of diseases with this species, revealing the importance of ZF as an experimental model for the screening of natural products. Key words: Danio rerio, experimental models, natural products.

Evaluation of antidiabetic effect and hematotological profile of methanol extract of Ceiba pentandra G (Malvaceae) stem bark on alloxan-induced diabetic rats

Abstract: The anti-diabetic effect of methanol extract of stem bark of Ceiba pentandra and its beneficial/ toxicological effect on hematological parameters in normal and alloxan-induced-diabetic rats were studied. The acute toxicity (LD50­) test and phytochemical analysis were also carried studied. The diabetic rats were divided into five groups of 5 animals each given oral administration of the extract daily for 14 days. The antidiabetic study was carried out using 200, 400, and 800 mg/kg body weight of C. pentandra extract. The methanol extract of C. pentandra significantly (p < 0.05) reduced the blood glucose level in diabetic and norm glycemic rats in comparison with glibenclamide (standard drug). The effect of C. pentandra at 800 mg/kg (33.6%) was more effective compared to glibenclamide (23.0%) in lowering blood glucose with the added benefit of restoring reduced hematological parameters in diabetic rats to near normal level in norm glycemic rats. The acute toxicity (LD50­) test of the methanol extract was found to be greater than 5000 mg/kg. This showed the extract is relatively safe. The plant is also rich in flavonoids, saponins, resins, terpenoids, glycosides, and tannins. The result of this study shows that C. pentandra does possess anti-diabetic activity, beneficial effect and hence can ameliorate hyperglycemia and anemia in alloxan-induced diabetic rats establishing its potential as a source for isolation of new oral antihyperglycaemic agents. Key words: Ceiba pentandra, hyperglycemia, hematology, diabetes.

In vitro antioxidant activity and phenolic contents of different fractions of ethanolic extract from Khaya senegalensis A. Juss. (Meliaceae) stem barks

Abstract: Khaya senegalensis A. Juss (Meliaceae) is a medicinal plant used in folk medicine of Burkina Faso. Its stem barks are used to treat several diseases such as inflammation, arthritis, infections, ulcer, malaria, fever and dermatosis. The antioxidant activity of aqueous ethanol extract and fractions of Khaya senegalensis stem bark was evaluated using 2,2-diphenyl-1-picrylhydrazyl (DPPH•), 2,2'-azino-bis (ABTS•+), ferric reducing antioxidant power (FRAP) and lipidic peroxidation methods. Total phenolic, tannins, flavonoids and flavonol contents of extract and fractions were determined. Butanol fraction had the highest value with IC50 =1.76 ± 0.19 µg ml-1 (ARP = 0.56) with DPPH• assay, however n-hexan fraction showed the highest capacity to scavenge ABTS•+; FRAP values varied from 13.04 ± 0.25 to 13.60 ± 0.09 mmol Trolox Equivalent per gram (mmol TE g-1) of extract or fraction. Ethyl acetate fraction presented the best activity (70.30 ± 0.40%, 100 µg ml-1) using lipid peroxidation inhibition method. Aqueous fraction contained the highest of total phenolics and tannins contents with, respectively 3.68 ± 0.11 and 2.65 ± 0.18 g TAE/100 g of dry weight (dw) of plant material. Aqueous fraction also showed the highest of total flavonoids (0.04 ± 0.01 g QE/100 g dw) and flavonol (0.10 ± 0.01 g QE/100 g dw) contents. K. senegalensis possesses a potential antioxidant effect and contains phenolic compounds. These results provide scientific evidence that validates the use of K. senegalensis in traditional medicine. Key words: Khaya senegalensis, antioxidant, phenolic, flavonoids, tannins

Cytotoxic effect of Plectranthus neochilus extracts in head and neck carcinoma cell lines

Abstract: Following a tendency of studying the potential effects of plant extracts to cancer, this study aimed to evaluate in vitro the cytotoxic activity of Plectranthus neochilus (PN) extracts and its fractions in head and neck squamous cell carcinoma (HNSCC) cell lines and assess their tumor specificity. MTT assay was conducted with two HNSCC cell lines, FaDu (hypopharynx carcinoma) and SCC-25 (tongue carcinoma), one keratinocyte (HaCat) and one fibroblast (L929) cell line. Two PN leaf crude extracts, one ethanolic (E) and one hexanic (H), and their nine fractions were tested. A dose-response curve was performed with hexane PNH fraction and a tumor specificity index (TSI) was calculated. For all cell lines studied, almost all extracts and fractions resulted in cell viability lower than 50%. Hexane and methanol PNH fractions were exceptions, causing a significantly low viability in SCC-25 (17.16 and 34.53%, respectively), but higher than 50% in FaDu, HaCat and L929. The dose-response curve with hexane PNH fraction resulted in a CC50 of 540.9 µg/mL for FaDu, 550 µg/mL for L929, 762.1 µg/mL for HaCat and 274.2 µg/mL for SCC-25. The TSI L929/FaDu was 1.01, HaCat/FaDu was 1.40, L929/SCC-25 was 2.00 and HaCat/SCC-25 was 2.77. TSIs indicate its specificity for tongue carcinoma cells, when compared to fibroblasts and keratinocytes. Key words: Head and neck, squamous cell carcinoma, extract, cytotoxicity, cell line.

Biotransformation of coumarins by Cunninghamella elegans

Abstract: Microbial biotransformation of coumarin (I) was undertaken using a battery of twenty five microorganisms. Among them, the fungus Cunninghamella elegans NRRL 1392 was the sole microbe that efficiently metabolized coumarin (I) into umbelliferone (II), 3, 4-dihydrocoumarin (V) and transcinnamic acid (VI). Umbelliferone was also biotransformed into 6, 7-dihydroxycoumarin (aesculetin, VII) and p-coumaric acid (VIII). On the other hand, warfarin (III) was biotransformed into 4`-hydroxywarfarin (IX) and also dicoumarol (IV) was transformed into 4-hydroxycoumarin (X) by the same microorganism. The structures of the metabolites were established using only one property and spectroscopic techniques including melting points, 1H NMR, 13C NMR and mass spectroscopy. The cytotoxic effect of coumarin substrates and their metabolites was also investigated. Key words: Biotransformation, coumarins, Cunninghamella elegans, cytotoxic.

In vitro acaricidal activity of crude extracts of Schinus molle (L.) leaves against field population of Bophilus decoloratus and Rhipicephalus pulchellus ticks

Abstract: Plant products are a rich source of bioactive organic chemicals and offer an advantage over synthetic pesticides as these are less toxic, less prone to development of resistance and easily biodegradable. The present study aimed at screening the acaricidal potential of crude methanolic and aqueous extracts of Schinus molle (L.) leaves on the adult Bophilus decoloratus and Rhipicephalus pulchellus cattle ticks, using in vitro immersion method. Freshly collected adult ticks were exposed to three graded concentrations of the crude extracts; 1% (1g/100ml), 2% (1g/50ml), and 4% (1g/25ml) for 24 h and mortality rates were recorded post exposure for each concentration every 3 h. Diazinon (0.2%) and distilled water were used as positive and negative controls respectively. Acaricidal activities of each concentration were measured by mean number of ticks died and antiparasitic efficacy (%) relative to the negative control. Analysis result indicated that highest (4%) and middle (2%) concentrations of both extracts caused a statistically significant (P<0.05) killing effect on R. pulchellus and B. decoloratus for most of the observation hours as compared to the extract unloaded in vitro groups. The relative antiparasitic efficacy (%) was highest for 4% concentration of both extracts (100%). The standard acaricide failed to completely eliminate the parasites after 24 h of exposure although it showed a slightly better effect against B. decoloratus (96.7%) compared to R. pulchellus (93.3%). Put together, this finding showed that the crude extracts of the plant have promising acaricidal properties and warrant further investigation. Key words: Acaricidal, crude extracts, Boophilus decoloratus, Rhipicephalus pulchellus, Schinus molle.

A review on corrective action and preventive action (CAPA)

Abstract: The primary objective behind corrective action and preventive action (CAPA) in any pharmaceutical or medical device industry is to determine the weakness, deviation or failures and to carry out its investigation with appropriate actions so that such problems are not repeated again. CAPA is also a method in which preventive measures are taken in the beginning itself so that occurrence of any incidence can be prevented. It is a part of overall Quality Management System (QMS) and also a regulatory requirement in a pharmaceutical company. Keywords: Corrective action, preventive action, corrective action and preventive action (CAPA), action plan, root cause determination.

Centratherum anthelminticum seeds reverse the carbon tetrachloride-induced hepatotoxicity in rats

Abstract: The present study is the first attempt to evaluate the hepatoprotective effect of ethanolic seeds extract (ESEt) of Centratherum anthelminticum (black cumin) in carbon tetrachloride (CCl4)-induced liver injury. The test doses (600 and 800 mg/kg) of same extract were found effective in their respective test groups by improving the body and liver weights, serum alanine and aspartate transaminases, γ-glutamyltranspeptidase, alkaline phosphatase, total proteins, albumin, total bilirubin, especially indirect bilirubin and uric acid levels as compared to CCl4-induced hepatotoxic control group. In addition, decreased percent inhibitions of antioxidant parameters including catalase, superoxide dismutase and reduced glutathione accompanied with increased percent inhibition of lipid peroxidation observed in both test groups. Histopathological studies also proved the liver regenerating property of ESEt by showing decrease in fatty deposition, necrosis and inflammation around the central vein of liver lobules. Therefore, the ESEt was found to be hepatoprotective and antioxidative in nature. Key words: Centratherum anthelminticum, Carbon tetrachloride, Liver function test and antioxidants.

In- vivo and vitro bioactivities of the essential oil of Duguetia lanceolata branches

Abstract: The present study investigated the in- vivo and vitro bioactivities of the essential oil of Duguetia lanceolata branches (EODL) and caryophyllene oxide (CO). The chemical composition of EODL was analyzed by GC and GC/MS. Acetic acid-induced writhing, formalin, hot plate and tail-immersion methods were used to evaluate the antinociceptive effect in mice. Anti-inflammatory activity was tested by carrageenan-induced paw edema and pleurisy in rats, and in mouse models of acute ear inflammation induced by croton oil and arachidonic acid. 2,2-Diphenyl-1-picrylhydrazyl (DPPH), reducing power and 𝛽-carotene bleaching assays were used to determine the antioxidant bioactivity. i¢-Elemene, caryophyllene oxide and i¢-eudesmol were the major components found in EODL. When tested, EODL and CO reduced the number of writhes and both phases of the time of paw licking, while the reaction time on a hot plate and the pain latency duration by the tail-immersion assay were increased. EODL and CO were effective against the paw edema, exudate volume, leucocyte migration and ear edema. EODL and CO also showed in vitro antioxidant activity. These results suggest that caryophyllene oxide is one of the active compounds found in EODL and could partially justify the bioactivity of this oil. Key words: Duguetia lanceolata, essential oil, caryophyllene oxide, antinociceptive activity, anti-inflammatory activity, antioxidant activity.

Did drug availability in Malawian central hospitals improve after the conversion of central medical stores to a trust

Abstract: Malawian public hospitals have reportedly been experiencing a lot of shortages in medicines and medical supplies in recent years. This was at least in part, attributed to the traditional placement of the drug supply system under the Ministry of Health, and therefore a change in the organizational set-up was implemented in 2011. This study aimed at finding out if the availability of medicines in central hospitals in Malawi improved after the change of Central Medical Stores (CMS) to a Trust (CMST). A retrospective cohort study was done to quantify the availability of selected essential medicines before and after the change of CMS from stock cards. A questionnaire was filled by 23 health professionals to assess their views on whether the change of CMST resulted in improved availability of medicines. The study was done at Queen Elizabeth Central Hospital (QECH), Kamuzu Central Hospital (KCH) and Central Medical Store Trust. The targeted study period was before the change of CMS (2010/2011) and after (2013/2014) the change to CMST. The results of the study showed considerable reduction in stock-out days for both KCH and the CMST (from an average of 80 and 16 days to 42 and 9 days, respectively), with CMST results being statistically significant (p=0.023). However, in QECH, there was no improvement (from 22 to 24 days). The view of most respondents was that there was no improvement in medicine availability after the change of CMS, which represented a certain contradiction to the results of the quantitative part. This may be attributed to the fact that the questionnaire targeted only participants from QECH and KCH and left out participants from CMST. The study indicated that the radical shift in the management of CMS was followed by an improvement of drug availability in CMST itself, and in one of the two investigated hospitals. The non-improvement in drug availability in hospitals calls for further investigation in the future to understand the reasons for this. Key words: Central medical stores, Malawi, medicine availability, essential medicine, autonomous supply agency, pharmaceutical logistics, supply chain.

Studies on gastrointestinal properties of ethanolic leaf extract of Salacia lehmbachii in Wistar rats

Abstract: Salacia lehmbachii Loes, is used traditionally in Nigeria for the treatment of gastrointestinal disorders. The aim of this study was to investigate the anti-ulcer and anti-diarrhoeal activities of the ethanolic leaf extract of S. lehmbachii. The ethanolic leaf extract was evaluated for castor oil-induced diarrhoeal, intestinal transit as well as intestinal fluid accumulation in rats, while indomethacin, water immersion stress-induced and histamine were used for anti-ulcer tests. The extract at the doses used significantly (P<0.05) decreased castor oil-induced diarrhoea in rats as judged by a decrease in the number of wet faeces in the extract treated rats. Moreso, the leaf extract inhibited the propulsive movement of intestinal contents. S. lehmbachii also showed a dose-related inhibitory activity on castor oil-induced intestinal fluid accumulation in rats. The leaf extract of S. lehmbachii significantly (P<0.05) reduced the ulcer index in all assays used. The results of the current study support the folkloric usage of S. lehmbachii leaf extract in the management of gastrointestinal disorders in Nigerian herbal traditional medicine. Key words: Salacia lehmbachii, leaves, herbal medicine, antidiarrhoea, antiulcer, rats.

Supercritical fluid and pharmaceutical applications. Part I: Process classification

Abstract: The supercritical fluid technology has been target of many pharmaceuticals investigations in particles production for almost 35 years. This is due to the great advantages it offers over others technologies currently used for the same purpose. A brief history is presented, as well the classification of supercritical technology based on the role that the supercritical fluid (carbon dioxide) performs in the process. Key words: Supercritical fluid technology, supercritical carbon dioxide, pharmaceuticals.

Neuropharmacological profile of ethanolic dried seed extract of Persea americana in mice

Abstract: Persea americana Mill (Lauraceae) is a medicinal plant used traditionally in Nigeria to treat several diseases including malaria, hypertension and febrile convulsions among others. Some of these indications are related to central activity but have not been systematically evaluated. This study investigated the neuropharmacological effects and the acute toxicity profile of the ethanolic dried seed extract of P. americana in mice. Fresh dried grounded seed of P. americana was extracted with 70% ethanol. Acute toxicity (LD50) profile of the ethanolic extract of P. americana (EEPA) at 10 to 5000 mg/kg was determined orally (p.o.) and intraperitoneally (i.p.) in mice. The EEPA was further tested for behavioral, anxiolytic, hypothermic, sedative, anticonvulsant, and anti-nociceptive activities. The LD50 of EEPA was determined to be ≥5000 mg/kg, p.o., and 2250 mg/kg, i.p. The extract at 250 to 1000 mg/kg dose-dependently caused significant (p<0.01 to 0.001) reduction in rearing and locomotor activity, signifying central nervous system (CNS) depression; significantly (p<0.01) lowered normal rectal temperature showing hypothermic effect; shortened onset and increased total sleeping time of ketamine (100 mg/kg, i.p.), suggesting sedative activity; reduced mortality due to pentylenetetrazole, picrotoxin and strychnine, and blocked hind limb tonic extension on the electro-shock, conveying evidence of anticonvulsant activity; increased reaction time on the hot plate and inhibited acetic acid-induced writhings, indicating analgesic potential. This study reveals significant depressant effect of ethanolic extract of P. americana on the CNS; and manifested hypothermic, sedative, anticonvulsant and anti-nociceptive effects in mice, thus justifying its ethnomedicinal use which can also serve as a lead in drug discovery. Key words: Avocado, behavioral, hypnosis, anticonvulsant, nociception.

Antibacterial and antifungal activities of indican (indoxyl -D-glucoside)

Abstract: Indican (Indoxyl β-d-glucoside), plant pigments found in true Indigo, are present in Indigofera genus plants, fungi and human urine. This study evaluated the antibacterial and antifungal activities of this pigment using the microdilution method. Antibacterial and antifungal activities were performed against Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, Candida albicans, Candida tropicalis, Candida krusei, Trichophyton rubrum, Trichophyton mentagrophytes and Microsporum gypseun. Minimum inhibitory concentrations (MICs) were measured according to the broth microdilution protocols by the Clinical and Laboratory Standards Institute (CLSI). The Indican showed only antifungal activity. It had MIC values of 128 µg/mL for yeasts and 512 µg/mL for most of the dermatophytes. The minimum fungicidal concentration (MFC) values of the Indican ranged between 512 μg/mL: C. tropicalis (LM-6) and C. krusei (LM-6 and LM-8) and 1,024 μg/mL: C. albicans (ATCC-76645, LM-108, LM-P20). Further studies are needed to clarify the potential fungicidal activity of the Indican and the possibility for topical applications. Key words: Antibacterial activity, antifungal activity, indican.

In vivo antioxidant and lipid peroxidation effect of various extracts from aerial parts of Chomelia asiatica (Linn) in rat fed with high fat diet

Abstract: The present investigation was to examine the in vivo antioxidant activity and lipid peroxidation activities of different extracts of aerial parts of Chomelia asiatica (Linn). High fat diet rats demonstrated fundamentally decreased the levels of tissues enzymatic antioxidant and non-enzymatic antioxidant (Glutathione). The level of thiobarbuturic acid reactive substance (TBARS) is reduced in high-fat diet (HFD) rats when compared and control group. Administration of ethyl acetate extract of Chomelia asiatica in high fat diet rats were indicated altogether (p<0.001) increased the levels of antioxidant enzymes, for example, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR) and level of non enzymatic antioxidant glutathione (GSH) when contrasted and HFD rats (Group II). The ethyl acetate extract of C. asiatica in high fat diet rats were discovered lowered the concentration of TBARS when contrasted and HFD rats. In comparison of all the three extracts treated group with standard group, the ethyl acetate extract of C. asiatica showed significant (p<0.001) result than that of other groups. Taking into account the outcomes, we concluded that the ethyl acetate extract of C. asiatica is a significant source of antioxidant, which may be useful in keeping the advancement of different oxidative stresses. Key words: Chomelia asiatica, in vivo antioxidant, lipid peroxidation, rats.

Euterpe oleracea Mart. (aai): an old known plant with a new perspective

Abstract: The acai (Euterpe oleracea Mart) fruit pulp is extensively used in Brazil as food among other uses. The health benefits of acai are largely reported by the Amazon inhabitants. Nonetheless, just a few pharmacological and toxicological studies were made to probe the innocuousness and the safety of the use of this product. The aims of this work were to update knowledge about the chemical composition, pharmacological and toxicological studies of the fruits and to identify possible vacuum of knowledge in the use, evaluation, and characterization of E. oleracea Mart (Acai) as a promising Amazon superfruit. It was made a draw out internet revision, especially in databases as NCBI, SCOPUS, PUBMED, SCIELO, and ELSEVIER by using the keywords E. oleracea, acai, nutraceuticals and food supplementations. Also, it was looked for each one of the ethnobotanical uses reported for this plant species combined with the first keywords. A complete record of the chemical composition of this species was achieved. Just two studies in humans were found in the literature using the acai fruit pulp. There is no sufficient systematic evidence to assure that all of the ethnobotanical uses of this species are true. A great emptiness of scientific knowledge related to the real benefits of this plant species exist. There exist neither pharmaceutical forms nor standardized product derived from the acai fruit. Until now, the number of scientific studies that allow the validaton of the ethnopharmacological practices, the innocuousness and the safety of the use of this plant fruit is insufficient. Key words: Euterpe oleracea, acai, nutraceutical, food supplementation.

Biochemical and histological evaluation of benzo[a]pyrene induced nephrotoxicity and therapeutic potentials of Combretum zenkeri leaf extract

Abstract: This study determined the therapeutic effect of ethanol leaf extract of Combretum zenkeri on kidney function of rats exposed to benzo[a]pyrene. Male Wistar albino rats were treated with ethanol leaf extract of C. zenkeri (400 mg/kg) in the presence or absence of BaP (200 mg/kg) for four weeks. The blood obtained at the end of the treatment was processed into serum and used for biochemical analyses and kidney tissues for histology. The serum creatinine, urea, sodium ion and potassium ion concentrations of the group exposed to benzo[a]pyrene without treatment with C. zenkeri extracts were significantly higher (p<0.05) as compared to the normal control group. The kidney histology indicated severely damaged glomeruli. The groups treated with the leaf extract pre- or post- benzo[a]pyrene exposure showed significant reduction (p<0.05) in serum concentration of urea, creatinine and sodium ion, while the pre-treated group showed no significant reduction (p<0.05) in serum potassium ion concentration. The biochemical and histological studies indicated that, C. zenkeri can ameliorate benzo[a]pyrene induced oxidative kidney damage. Key words: Combretum zenkeri, benzo[a]pyrene, PAHs, oxidative damage, kidney functions.

Study of the self-association of amoxicillin, thiamine and the hetero-association with biologically active compound chlorgenic acid

Abstract: The self-association of amoxicillin (AMX) and its hetero-association with biologically active compound, chlorogenic acid (CGA) were investigated at room temperature (295°K). The dimerization constant of amoxicillin and thiamine (THIA) analyzed using the dimer model at the wavelength of 278 and 256 nm were found to be and , respectively. The hetero-association constant of amoxicillin and chlorogenic acid analyzed using Benesi-Hildebrand approach were . Thermodynamic parameters such as Gibbs free energy, enthalpy and entropy of dimerization reactions for the self-association and hetero-association of the compounds were also investigated using Vant’s Hoff equation at the temperature ranges (295 to 305°K). The change of enthalpy calculated for amoxicillin, thiamine and the complexes of amoxicillin-chlorogenic acid are 34.73±2.17, 54.1±4.585, and 6.988±0.493 at the temperature of 305°K, respectively. The values of change in enthalpy and entropy indicate that the hydrophobic interaction play the major role in the interaction between the molecules. Key words: Amoxicillin, thiamine, chlorogenic acid, UV-Vis spectroscopy, thermodynamic, self-association, hetero-association.

Ameliorative effect of grape seed extract on metabolic disorders caused by high fat diet induced obesity in rats by reversing the increase in hepatic miR-33a and miR-122

Abstract: MiR-33a and miR-122 are major regulators of lipid metabolism in the liver and their deregulation has been linked to the development of metabolic diseases such as obesity and metabolic syndrome. The aim of this study was to evaluate whether the level of miR-33a and miR-122 in rat liver correlate with obesity and potential anti-obesity effect of grape seed extract (GSE) and calorie restricted diet with special emphasis on dyslipidemia, oxidative stress and inflammation. Rats received high fat diet (HFD) for four months to induce obesity. Animals which had ≥30% increase in body weight were selected in this study. Obese rats were divided into 4 groups (n=12/each) and treated for 8 weeks with caloric restriction, GSE (30 mg/kg daily orally) alone or in combined form. Obese rats developed increased body weight and up-regulation of miR-33a and mir-122 in the liver. Also obesity provoked dyslipidemia, oxidative stress and inflammatory status. Importantly, GSE alleviated all deleterious effects of HFD especially when administered with calorie restricted diet. They counteracted the increase of these two miRNAs with improvement in dyslipidemia, oxidative and inflammatory processes. The results reported suggested that beneficial metabolic effects of GSE in combination with dietary treatment could be useful to treat obesity and metabolic disorders. Key words: Obesity, GSE, dyslipidemia, oxidative stress, hepatic miRNAs

Phytochemical and efficacy study on four herbs used in erectile dysfunction: Mondia whiteii, Cola acuminata, Urtica massaica, and Tarenna graveolens

Abstract: There is a resurgence in the use of herbal medicine in the developed countries, with even much more in low developed Countries and especially for conditions such as erectile dysfunction. Studies thus need to be conducted to scientifically validate claims on certain medicinal plants reported to be efficacious in traditional medicine. This current study was conducted to determine the phytochemical composition and efficacy of four herbs Mondia whiteii (Hook. F.) roots locally called (Mulondo), Cola acuminata (P. Beauv.) fruits locally called (Engongoli), Urtica massaica (Mildbr) leaves, locally called (Engyenyi) and Tarenna graveolens (S. Moore) roots, locally called (Munywamaizi) in Runyankole which have been reported as remedies for the management of erectile dysfunction in South-western Uganda. Phytochemical screening was conducted following methods described in Kokate, Trease and Evans. Sexual function was tested using both the contact and non-contact model. Arginine was present in all the extracts. Aqueous extract of Tarenna graveolens significantly improved testosterone levels but none of the extracts had significant effects on mounting frequency. Aqueous extract of Tarrena graveolens could be useful in management of erectile dysfunction associated with hypogonadism. Key words: Erectile dysfunction, efficacy, phytochemical, testosterone, Mondia, Cola, Urtica, Tarenna.