PHARMACEUTICAL SCIENCES
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- ItemEFFECT OF CO-ADMINISTRATION OF METFORMIN AND CEFIXIME ON SOME BIOMARKERS IN DIABETIC RATS(2011-05)The incidence of infections in Type 2 Diabetes Mellitus (T2DM) continues to be on the increase, necessitating the combined use of antibiotics and hypoglycaemic agents. Metformin, a biguanide is the first drug of choice in the management of T2DM and is most frequently employed with antibiotics when infections exist as co morbid state. This study investigated the effect of Metformin (200 mg/kg) and Cefixime (400 mg/kg) in alloxan (140 mg/kg) induced diabetic rats. Metformin was administered orally for 28 days alone and 14 days co-administration with Cefixime and the effect on some metabolic biomarkers were recorded. The effect of combination of Metformin 4μg/ml, 2μg/ml and 1μg/ml on in vitro antimicrobial activities of Cefixime 5μg/ml against K. species, P. mirabilis, H. influenza and E.coli was also investigated. There was a statistically significant reduction (p<0.05) in Fasting Blood Glucose (FBG) on Day 28 and Random Blood Glucose (RBG) (p<0.01) on day 21 of diabetic rats in Metformin/Cefixime group compared to Metformin alone group. There were no statistically significant changes in the haematological (WBC, RBC and PCV) and biochemical (urea, creatinine and electrolytes) parameters studied. There was no significant difference in body weight and relative weights of selected organs in the drug treated groups and the control. Histopathological findings revealed various degrees of pathological changes in the liver and kidney of the diabetic rats in Metformin and Metformin/ Cefixime group. The pancreas showed areas of pancreatic acini with less cellular endocrine portion in Metformin alone group. Metformin did not significantly alter the in vitro antimicrobial activities of Cefixime against the selected Microrganism used in this study. The study showed that Cefixime may slightly increase the hypoglycaemic activity of Metformin when co-administered. This effect may not appear to be of much clinical significance when both drugs are administered at therapeutic doses, but will call for caution when used for a longer period or in other situations predisposing patients to possible accumulation of Metformin.
- ItemPHYTOCHEMICAL, ANALGESIC AND ANTI-INFLAMMATORY STUDIES ON THE METHANOL ROOT EXTRACT OF COMBRETUM HYPOPILINUM (DIELS) OKAFOR (COMBRETACEAE).(2022)Combretum hypopilinum (Diels) Okafor belongs to the family Combretaceae, and composed of 20 genera with about 500 species. It is a small to medium sized, deciduous shrub or tree growing from 4 - 18 metres in height, with a rounded or flat heavy crown. The plant is used in ethnomedicine for the treatment of pain, snake bites, jaundice, gonorrhoea, gastrointestinal disorder, infertility, tuberculosis and as blood tonic. The aim of the study is to isolate and characterize some of the phytochemical constituent present in the methanol root extract of combretum hypopilinum and to screen the extract for analgesic ant ant-inflammatory activity in mice and rats. The methanol root extract of the plant was subjected to phytochemical screening as well as analgesic and anti-inflammatory studies. The preliminary phytochemical screening of the methanol root extract of Combretum hypopilinum revealed the presence of steroids/triterpenes, flavonoids, tannins, cardiac glycosides, alkaloids, carbohydrates and saponins. The methanol root extract was partitioned successively with chloroform, ethyl acetate and acetone in order of increasing polarity to yield different fractions. Column chromatography separation of ethyl acetate fraction led to the isolation of stigmasterol and Lupeol which are white powdered and white crystalline material with melting points range of 169-1710C and 212-2140C respectively. The structures of these isolated compounds were elucidated using physical test, chemical test, IR and NMR analysis. The intraperitoneal LD50 of the extract was found to be greater than 5000 mg/kg body weight which implies that the extract is relatively safe. The analgesic activity was determined using acetic acid induced writhing, hot plate tests in mice while the anti-inflammatory activity was investigated using carrageenan- induced paw edema test in rats. The extract significantly and dose dependently inhibited the acetic acid-induced writhing in mice. However, the highest protection against writhing was produced by the MRE at a dose of 1000 mg/kg (66.58 %) when compared to the standard drug 69.57 %. The extracts at dose of 500 mg/kg at 90 min showed a significant (P<0.05) increase in the mean reaction time using hot plate method. The carrageenan induced paw oedema was employed in investigating the anti-inflammatory activity in rats. The extract showed significant decreases in paw edema at 4 -5 h of carrageenan injection at all doses tested when compared to the control group at (P<0.05). These results thus, justify the use of the plant in ethnomedicine for the treatment of pain and inflammation. The biological activity might be as a result of the presence of bioactive phytoconstituents present in the methanol root extract
- ItemPHYTOCHEMICAL AND ANTI SNAKE VENOM STUDIES ON THE METHANOL AERIAL PART EXTRACT OF TACAZZEA APICULATA OLIV (PERIPLOCACEAE)(2022)Tacazzea apiculata (Olive) is a woody climber indigenous to Tropical Africa often used in traditional medicine for the treatment of pain, inflammation, skin infections, diabetes, epilepsy and snakebite. This study aimed to isolate and characterize some of the phytochemical constituent(s) present in aerial part extract of T. apiculata and to scientifically validate the ethno medicinal claim of the use of the plant in the management of snakebite envenomation. The powdered aerial part of T. apiculata was extracted with methanol using maceration method which afforded methanol aerial part extract (MAE). Portion of this was treated with n-hexane, chloroform and ethyl acetate to obtain n-hexane (HEF), chloroform (CHF) and ethyl acetate fractions (EAF). Preliminary phytochemical screening of the methanol extract revealed the presence of secondary metabolites including alkaloids, flavonoids, saponins, tannins, and steroids/triterpenes. Silica gel chromatographic separation of chloroform fraction (CHF) afforded total of eleven major fractions C1 – C11, fractions C2 and C5 were subjected to further silica gel chromatographic separation which resulted to C2A and C5C sub fractions respectively. Repeated purification of C2A using silica gel packed column (micro pipette) eluted with n-hexane 100 % isocratic led to the isolation of a brown oily compound Tam 4. Similarly, repeated purification of C5C using silica gel packed column (micro pipette) eluted with n-hexane: ethyl acetate (8:2) isocratic resulted in the isolation of a white powdered compound Tam 2. The structures of the compounds were elucidated using physico-chemical tests and spectroscopic techniques (IR, 1D and 2D NMR) and by comparison with reference spectral data. The oral and intraperitoneal route LD50 of the methanol aerial part extract (MAE) in mice were estimated to be 5000 and 894 mg/kg, respectively. The LD99 of the Naja nigricollis venom was estimated to be 4.6 mg/kg. Antivenin studies suggest that methanol extract possess significant antivenin activity against Naja nigricollis venom both ex-vivo and in-vivo with maximum protections level of 100 % survival at 80 mg/kg dose and 16.67 % survival at 2000 mg/kg dose respectively. Spectral analysis of both Tam 4 and Tam 2 by way of NMR showed Tam 4 to be Squalene and Tam 2 β-sitosterol. The structures were confirmed with the literature data and methanol extract demonstrated significant antivenin activity and lends credence to traditional use of the plant in the management of snakebite.
- ItemEFFECT OF LAURIC ACID ON ERECTILE AND TESTICULAR DYSFUNCTION IN DIABETIC MALE WISTAR RATS(2022)Diabetes mellitus is a risk factor for reproductive and sexual dysfunction. Standard medications are not completely satisfactory, hence the consideration of natural products as an alternative therapy. Lauric acid is the most abundant constituent of coconut oil, which is renowned for its therapeutic properties. This study sought to investigate the influence of lauric acid on testicular and erectile function in diabetic male Wistar rats. Seventy male rats (150-200 g) were divided into seven groups of ten each. Group 1 (NC): Normal control. Group 2 (DM-UT): Diabetic untreated. Group 3 (DM + LA 90): Diabetic treated with Lauric acid (90 mg/Kg). Group 4 (DM + LA 180): Diabetic treated with lauric acid (180 mg/Kg). Group 5 (DM + LA 360): Diabetic treated with lauric acid (360 mg/Kg). Group 6 (DM + CO): Diabetic treated with coconut oil (1.42ml/kg). Group 7 (DM + Sild): Diabetic treated with sildenafil (20 mg/Kg). Diabetes was induced by an intraperitoneal injection of streptozotocin (65 mg/Kg). Treatments were administered orally for four weeks after which the animals were euthanized. Gonadosomatic index, semen analysis, testicular histology and serum testosterone assay were then carried out. The corpus cavernosum was also extracted and contractile responses to phenylephrine and KCl; relaxant responses to acetylcholine and sodium nitroprusside (SNP); relaxation response to lauric acid in the presence of L-NAME; and contraction response to Ca2+ in the presence of lauric acid were evaluated. The gonadosomatic index in NC and DM + CO rats was significantly higher (p ˂ 0.05) compared to the other groups. Serum testosterone in all groups were respectively lower (p ˂ 0.05) compared to NC. Sperm count in NC and DM + CO rats respectively were significantly higher (p ˂ 0.05) compared to the other groups. The percentage of motile sperm cells in NC and DM + CO groups were significantly higher (p ˂ 0.05) compared to the other groups: The percentage of progressively motile sperm groups were significantly lower (p ˂ 0.05) compared to NC. The percentage of progressive motile sperm cells in DM + LA 90 and DM + CO were significantly higher (p ˂ 0.05) compared to DM-UT. The percentage of normal sperm cells in NC rats was significantly higher (p ˂ 0.05) compared to all the other treatment groups. The percentage of normal sperm cells in DM + LA 90, DM + LA 360, DM + CO, and DM + Sild were significantly higher (p ˂ 0.05) compared to DM-UT. The percentage of viable sperm cells in NC and DM + CO rats respectively were significantly higher (p ˂ 0.05) compared to other groups. Testicular histology showed degradation in DM-UT group and was considerably improved only in DM + LA 360 and DM + CO. Percentage contraction to KCl was significantly higher (p ˂ 0.05) in DM-UT and DM + CO rats respectively compared to the NC rats. The percentage relaxation of phenylephrine pre-contracted tissues to acetylcholine was significantly higher (p ˂ 0.05) in NC and DM + Sild rats compared to the other groups. The percentage relaxation of KCl pre-contracted tissues to acetylcholine was significantly higher (p ˂ 0.05) in NC and DM + LA 90 rats compared to the other groups. The percentage relaxation of phenylephrine pre-contracted tissues to sodium nitroprusside (SNP) was significantly lower (p ˂ 0.05) in DM-UT, DM + LA 360 and DM + CO rats compared to the NC rats. The percentage relaxation of KCl pre-contracted tissues to SNP was significantly lower (p ˂ 0.05) only in DM-UT rats compared to the NC rats. The percentage relaxation of phenylephrine pre-contracted corpus cavernosal tissues to lauric acid was significantly higher (p ˂ 0.05) in the presence of L-NAME compared to the control. The percentage relaxation of KCl pre-contracted cavernosal tissues to cumulative concentrations of lauric acid was significantly lower (p ˂ 0.05) in the presence of L-NAME compared to the control. It was therefore concluded that lauric acid rescued some but not all testicular dysfunctions in diabetic male rats. Lauric acid
- ItemDESIGN, SYNTHESIS, ANTIMALARIAL EVALUATION AND COMPUTATIONAL STUDIES OF SOME CHALCONE DERIVATIVES(2018-06)Inspired by the previous findings on the structural requirements needed for good antimalarial activity by chalcones against Plasmodium proteases, seventeen chalcone derivatives were designed and synthesized using Claisen-Schmidt condensation of appropriate aldehydes and methyl ketones. The structures of these compounds were established using various spectroscopic techniques. Based on SciFinder search the compounds; P1, P2, P3, and P8 are new compounds not listed on any chemical data base. The synthesized chalcones were screened in mice against established P. berghii infection. Eleven compounds were active and P2 the most active compound exhibited significant percentage inhibition of 90.32% (p˂0.05) at a dose of 100 mg/kg. An interesting observation was the demonstration of good antimalarial activity with the 3-quinolinyl A ring derivatives- P3, P4 and P8. The potential of the synthesized compounds to inhibit the synthesis of β-hematin was also evaluated but, only compounds P12 and P17 showed modest inhibition of β-hematin synthesis with percent inhibition of 59.28% and 49.04% respectively at a dose of 50 μg/kg. The prospects of dual inhibition of Plasmodium falciparum vital proteases; aspartic proteases (plasmepsin II and IV) and cysteine proteases (falcipain-2 and 3) of the seventeen chalcone derivatives was also investigated using in silico studies. Structure-based virtual screening using validated molecular docking revealed two potential hits (P3 and P4) with the best binding affinity and broad inhibition across all the proteases used. The crucial driving forces for receptor interaction and key interacting residues of the enzymes by the potential hits were established using molecular dynamics and binding free energy calculations. Simulation experiments revealed the stability of the docked ligands within all the enzymes. The ligands were found to interact with the residues at the active site and other sub-site regulating specificity for the falcipains system. With the plasmepsin systems, the ligands interact with the flap, covering the active site. From the different energetic contributions of the individual residues, it is evident that the binding process was principally favored by van der Waals and little affected by electrostatic energies while the polar solvation energy impaired it. With regard to the binding interactions, it appeared that the most contributing features of the ligands for receptor interactions are the quinoline ring, carbonyl group and 2- methoxy group. Therefore, the result from this work have identified quinolinyl chalcones with 2- methoxy substitution on ring B as potential candidates for further optimization as antimalarial against Plasmodium proteases.