Anti-fluoroquinolone resistance activity of E558: A natural product

Fluoroquinolone resistance (FQR) has paralleled the abuse of this class of antibiotics in Nigeria ever since the patent rights expired in 2003. However, nature has a potent way of uncoupling unfavourable synergies targeted against the serenity of the biosphere. In this preliminary study, we examined the antibacterial activity of E558, a medicinal plant product against multidrugresistant gram-negative isolates from immunocompromised patients with acute respiratory infections. The agar-well diffusion method was employed to screen for antibacterial activity against strains of Klebsiella pneuminiae, Escherichia coli and Pseudomonas aeruginosa. The organisms were initially subcultured on McConkey agar followed by streaking standard innoculum of the bacterial strains on Mueller-Hinton agar plates. A known concentration of crude extract was loaded into the well bored on the plates and then incubated at 37 °C for 24 hours. Antibiotic susceptibility testing (AST) was carried out to monitor resistance of isolates. Protein profiling with sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) as well as restriction endonuclease mapping with agarose gel electrophoresis was employed to study alterations in the genomic DNA of selected organisms. A reverse mutation was observed in the morphology of organisms exposed to E558 compared to the organism without exposure. AST result further revealed that strains in the reverted zone, which were originally resistant to fluoroquinolones and other antibiotics had become susceptible with very wide zone of inhibition (≥ 40 mm; CLSI-sensitive). Restriction mapping and SDS-PAGE respectively revealed there are major differences in the genomic composition and protein profile of the reverted strains when compared to the original organisms. It can therefore be deduced that E558 possibly contains bioactive compound(s) with potent antitumour and anti-fluoroquinolone resistance activity

Phytochemical and antimycobacterial analysis of aqueous and ethanolic extracts of Annona muricata Linn (Soursop)

Against the backdrop evidenced in the threat Tuberculosis poses to developing economies, especially its prevalence among people in their productive (15-45) years; this preliminary study examined the phytochemical constituents and antimycobacterial effect of four (4) aqueous and ethanolic extracts from the fruit skin (epicarp) and leaf of Annona muricata Linn

Effects of Quercetin on L-Arginine-Induced Acute Pancreatitis in Rats

This study evaluated the effect of quercetin on oxidative stress in a rat model of L-arginine-induced acute pancreatitis. Thirty male rats were randomly divided into five experimental groups thus: control, L-arginine group (2g/Kg body weight, i.p), and other groups were treated with 12.5mg/Kg body weight, 25mg/Kg body weight and 50mg/Kg body weight an hour after L-argnine administration. Twenty four hours thereafter, the rats were sacrificed and blood collected by cardiac puncture and organs were excised for the assay of plasma lipase and α-amylase activities as well as the activities of some antioxidant enzymes and levels of reduced glutathione, lipid peroxidation and chloramine. Acute pancreatitis was assessed by a significantly (p<0.05) increase in the activities of plasma lipase and α-amylase 24hours after L-arginine administration. All the quercetin dosages significantly (p<0.05) reversed the activities of these enzymes. L-arginine administration resulted in significant (p<0.05) reduction in the activity of glutathione-s-transferase in the lungs, pancreas and spleen as well as in the level of erythrocyte reduced glutathione. Only rats treated with 50mg/kg quercetin had a significant (p<0.05) reversal. However, all the quercetin treated groups had significant (p<0.05) increase in the level of erythrocyte reduced glutathione. Superoxide dismutase and peroxidase activities significantly (p<0.05) reduced while myeloperoxidase activity significantly (p<0.05) increased in the organs of rats as a result of L-arginine administration. These alterations were prevented by quercetin. These results show that quercetin protects the rat tissues from oxidative damage in L-arginine-induced pancreatitis.

Induction of rat hepatic mitochondrial membrane permeability transition pore opening by leaf extract of Olax subscorpioidea

has been implicated in the cascade of events involved in apoptosis (programmed cell death). Olax subscorpioidea is traditionally used for the treatment of several diseases and infection. However, its role on MMPT is not yet established. This study was aimed at evaluating the effects of varying concentrations of the methanol leaf extract of O. subscorpioidea (MEOS) on MMPT pore opening, mitochondrial adenosine triphosphatase (ATPase), and mitochondrial lipid peroxidation. Materials and Methods: Opening of the pore was spectrophotometrically assayed under succinate‑energized conditions. Results: In the absence of triggering agent (calcium), MEOS induced MMPT pore opening by 350, 612, 827, 845% at 36, 60, 86 and 112 µg/ml, respectively. MEOS further induced MMPT pore opening in the presence of a triggering agent by 866, 905, 831, 840, 949% at 12, 36, 60, 86 and 112 µg/ml, respectively. The extract significantly induced mitochondrial membrane lipid peroxidation in all the concentration used. MEOS also significantly increased mitochondrial ATP hydrolysis by mitochondrial ATPase in all concentration of the extract used. Conclusion: It may be deduced from this results, that MEOS contains certain bioactive components that may find use in pathological conditions that require an enhanced rate of apoptosi

Effects of Ginger Juice Aflatoxin-Induced Oxidative Stress in Rats

This study was carried out to investigate the antioxidant properties of the fresh juice of ginger against aflatoxin-exposure in rats. The preventive potential and antioxidant capacity of the juice was evaluated by assaying the activities of antioxidant enzymes and lipid peroxidation content in some organs and erythrocytes of rats. Twenty rats were randomly divided into four experimental groups thus: group 1 served as control, group 2 received ginger juice (2mL/Kg of 10% juice)alone, group 3 received aflatoxins (3.65mg/kg body weight) alone while group 4 was pre-treated with ginger juice for 7days prior to aflatoxin administration. In the erythrocytes, aflatoxin treatment resulted in significant (p<0.05) increase in erythrocyte osmotic fragility and lipid peroxidation with a concomitant significant (p<0.05) decrease in the level of reduced glutathione. Pre-treatment of rats with ginger juice significantly (p<0.05) prevent these changes by maintaining the activity of superoxide dismutase and preventing the increase in lipid peroxidation in the organs. Ginger juice pre-treatment also significantly (p<0.05) increased the activities of hepatic glutathione-S-transferase, peroxidase and superoxide dismutase. It is concluded that ginger juice has preventive effect in rats with aflatoxicosis by promoting the antioxidant defense systems

In silico Assessment of Antihypertensive Potential of Sweet Proteins (LB542)

The consumption of low-calorie artificial sweeteners by patients affected by diseases linked to sugar consumption may be associated with diverse side effects. Hence, sweet proteins derived majorly from under-utilized plants have been proposed as good replacements. The ability of sweet proteins to release Angiostensin-Converting Enzyme (ACE)-inhibitory peptides was investigated. ACE mediates arterial vasoconstriction and elevation of its activity is an important pathogenic mechanism of hypertension. The protein sequences of six sweet proteins, Thaumatin from Thaumatococcus danielli (NCBI accession number, gi|209473), Brazzein from Pentadiplandra brazzeana (NCBI accession number, gi|218218145), Monellin from Dioscoreophyllum cumminsii (NCBI accession number, gi|381144434), Madinlin from Capparis masaikai (NCBI accession number, gi|1817546), Curculin from Curculigo latifolia (NCBI accession number, gi|11225520) and Miraculin from Richadella dulcifica (NCBI accession number, gi|253735645) were selected for sequence alignment using Basic Local Alignment Search Tool (BLAST) analysis and biological activity search using BIOPEP. Although BLAST analysis gave no homologous similarity among the proteins, BIOPEP analysis showed that they demonstrated either di- or tri-peptide with a total of 51, 14, 40, 28, 30 and 59 potential ACE inhibitory peptides from Thaumatin, Brazzein, Monellin, Madinlin, Curculin and Miraculin respectively. The combined digestion with pepsin, trypsin and chymotrypsin A, a simulation of human gastrointestinal digestion released 8, 2, 9, 2, 5 and 11 ACE inhibitory peptides from Thaumatin, Brazzein, Monellin, Madinlin, Curculin and Miraculin respectively. These results add value to these proteins by demonstrating their innate nutraceutical potential in their ability to reduce hypertension. Table of Content

Gas Chromatography Mass Spectrometry Identification of Antiangiogenic Phytochemicals in Aframomum danielli K. Schum: An In silico Study

Aframomum danielli is one of the African spices used in folklore medicine for the management of several diseases. This study identified the phytochemical components present in the n-hexane seed extract of the A. danielli by gas chromatography-mass spectrometry (GC-MS) analysis and also evaluated the antiangiogenic potential of the identified phytochemicals by performing molecular docking against human Vascular Endothelial Growth Factor (VEGF) and matrix metalloproteinases (MMP) using Molegro Virtual Docker. The GC-MS analysis identified the presence of phytochemical components β-Caryophyllene (RT: 18.479), α-Caryophyllene (RT: 19.189), (4-Hydroxy-3-methoxyphenyl)ethyl methyl ketone (RT: 22.976), N-Acetyl-m-aminobenzoic acid (RT: 31.651) and 3-Pyridineacetic acid (RT: 32.446). (4-Hydroxy- 3-methoxyphenyl)ethyl methyl ketone were the strongest binding ligand (-65.744 kcal/mol for VEGF) and (- 99.7836kcal/mol for MMP) while β-Caryophyllene was the weakest binding ligand. These compounds showed relative strong docking to VEGF with docking energies comparable to an anticancer drug, bevacizumab (-77.883kcal/mol for VEGF) and (-109.021kcal/mol for MMP). This in silico molecular docking study has shown that these phytochemical components could be responsible for antiangiogenic properties of A. danielli

Acetaminophen Induces Mitochondrial Permeability Transition in Rats Without Causing Necrotic Liver Damage

Mitochondrial Permeability Transition (MPT) is reported as the mechanism of acetaminophen induced hepatic damage, however, rat models are resistant to acetaminophen induced toxicity. The occurrence and degree of mitochondrial permeability transition after treatment with 400 mg kgG1 of acetaminophen in albino Wistar rats were assessed. Animals were randomly distributed into seven groups; control, 12, 24, 36, 48, 60 and 72 h based on varying time (in hour) post acetaminophen prior to sacrifice after treatment. Mitochondrial Membrane Permeability Transition (MMPT) pore opening and mitochondrial cytochrome c release were estimated. Opening of MMPT pore and cytochrome c release were observed in 12, 24, 36 and 72 h, when compared with the control group. Liver function and histological results indicated no liver damage. It is concluded that toxic dose of acetaminophen induced mitochondrial permeability transition in rat hepatic tissues without leading to necrotic damage suggesting that rat hepatic tissues evade damage by mechanisms downstream of MPT

Investigation of Angiostensin-converting enzyme inhibitory potential and allergenicity of Sesamum indicum Linn seed proteins by an in silico approach (LB541)

The nutraceutical role of dietary proteins and peptides is gaining considerable interest in the management of cardiovascular disease like hypertension. In order to investigate the contribution of Sesamum indicum seed proteins to its antihypertensive properties was investigated, there seed protein sequences: 7S globulin (NCBI accession number, giǀ13183177), 2S albumin (NCBI accession number, giǀ13183174) and 11S globulin (NCBI accession number, giǀ13183172) were selected for BLAST, BIOPEP and allergenicity analysis. BLAST gave the following similarities: 7S globulin vs rice glutelin precursor (35%), 7S globulin vs oat 12S seed storage globulin 1 (29%), 11S globulin vs rice glutelin precursor (41%), 11S globulin vs oat 12S seed storage globulin 1 (39%) and 2S albumin vs oat 12S seed storage globulin 1 (60%). BIOPEP analysis showed that the sesame proteins demonstrated either di- or tri-peptide with a total of 92, 91 and 34 potential ACE inhibitory peptides from 7S globulin, 2S albumin and 11S globulin, respectively. Papain hydrolysis theoretically released the highest numbers of predicted ACE inhibitory peptides (23, 14 and 5) from 7S globulin, 2S albumin and 11S globulin, respectively. The 8-mer and 80-mer allergenicity analysis of these proteins showed significant matches with allergenic proteins from Lens culinaris, Anacardium occidentale, Carya illinoinensis. Although, the ccombined digestion with pepsin, trypsin and chymotrypsin A, a simulation of human gastrointestinal digestion, gave a sum of 32 predicted ACE inhibitory peptides from these proteins, their allergenic property may be a limitation