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International Journal of Biomedical and Pharmaceutical Sciences

Volume 1 Number 2 2007


Issue infomation


Keyvan Dastmalchi, H.J. Damien Dorman, Heikki Vuorela, Raimo Hiltunen (Finland) Plants as Potential Sources for Drug Development against Alzheimerfs Disease (pp 83-104)

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Invited Review: Alzheimerfs disease (AD) is a progressive, neurodegenerative disorder that primarily affects the elderly population and is considered to be responsible for ca. 60% of all dementia in people aged 65 or older. Due to its debilitating nature, an enormous social and economic burden is placed on society. The significance of AD is further compounded as the number of identified cases is estimated to double or triple by 2050. Currently there is no cure for the disorder and much of the treatments available have been able to only delay the progression of the disease or provide symptomatic relief for a short period of time. Therefore there is a need for a different approach to the treatment of these diseases. Plants have been used since antiquity in the treatment of various diseases including cognitive disorders, such as AD. Therefore ethnopharmacological screening of plants may provide useful leads in the discovery of new drugs for AD therapy. This article reviews screening of the plants, belonging to 21 families, used in traditional systems of medicine (e.g. Chinese, Indian and European) for treatment of cognitive dysfunction. Electronic data bases were used for searching information related to the studies done on the plants in the last 20 years. Phytochemical substances such as alkaloids, biphenolic lignans, curcuminoids, caffeic acid derivatives, diterpenes, triterpenoid saponins, triterpene lactones, stilbenes and withanolides with pharmacological activities relevant to AD treatment are discussed in this review. Compounds of potential interest for further drug developmental studies have been highlighted.

Shanmugam Kirubakaran, Annette Maczurek, Simon Young, Gerald Münch (Australia) -Lipoic Acid in the Treatment of Diabetic Polyneuropathy and Alzheimerfs Disease (pp 105-111)


Invited Review: -lipoic acid (LA) is a naturally occurring cofactor for mitochondrial enzymes, including pyruvate dehydrogenase (PDH) and -ketoglutarate dehydrogenase (KGDH). LA acts as a powerful micronutrient with diverse pharmacological properties. LA improves glucose uptake and insulin sensitivity, and thus decreases blood glucose levels and increases mitochondrial energy levels. LA chelates redox-active transition metals, thus inhibiting the formation of hydroxyl radicals from hydrogen peroxide and also scavenges reactive oxygen species, thereby increasing the levels of reduced glutathione. Via the same mechanisms, down-regulation of redox-sensitive inflammatory processes is achieved. Furthermore, LA can scavenge lipid peroxidation products such as hydroxynonenal and acrolein. LA is currently studied for the treatment of some neurodegenerative diseases with diverse pathophysiology, including diabetic polyneuropathy and Alzheimerfs disease. For diabetic polyneuropathy, LA has been used for decades in Germany with a number of clinical trials showing benefits in insulin-stimulated glucose uptake and attenuating symptoms of neuropathy. In Alzheimerfs disease, an open-label trial in patients with mild and moderate Alzheimerfs disease is currently conducted at a at the memory clinic of the Henriettenstiftung hospital in Hannover, Germany. Interim analysis of the data after 4 years show that the progression rate of the patient treated with 600 mg LA daily is significantly slower than to the non-treated control group - particularly in early stages of dementia - and other control groups in published studies.

Nathalie Wauthoz (Belgium), Aliou Balde, Elhadj Saïdou Balde (Guinea), Marc Van Damme, Pierre Duez (Belgium) Ethnopharmacology of Mangifera indica L. Bark and Pharmacological Studies of its Main C-Glucosylxanthone, Mangiferin (pp 112-119)


Invited Review: This review details the vernacular names, origin, distribution, taxonomy and variety of Mangifera indica L. (Anacardiaceae), a medicinal plant traditionally used in tropical regions. Mangiferin, a major C-glucosylxanthone from M. indica stem bark, leaves, heartwood, roots and fruits occurs widely among different angiosperm families and ferns. The reported pharmacological activities of mangiferin include antioxidant, radioprotective, antitumor, immunomodulatory, anti-allergic, anti-inflammatory, antidiabetic, lipolytic, antibone resorption, monoamine oxidase inhibiting, antiviral, antifungal antibacterial and antiparasitic properties, which may support the numerous traditional uses of the plant.

Sanjai Saxena, Devendra Kumar (India) Interaction between Human Pathogenic Bacteria and Plants: Possibilities of New Antimicrobial Drugs (pp 120-123)


Invited Research Note: Diverse metabolites are elaborated by plant roots which are being used as pharmacophores or drugs in treating cardiovascular diseases, as general tonics, anti-hypertensive, psychotropic agents, etc. These belong to different chemical classes from simple sugars to complex-like sesquiterpenes and alkaloids. The nature of exudates elaborated by the root or metabolites accumulated entirely depends upon the biotic and abiotic stresses faced during acquisition of nutrients and flourishing within the soil. With increasing incidence of human pathogens in the soil and in particular in the rhizosphere it becomes imperative to establish an interaction between the two under in vitro conditions for exploring the chemical diversity produced by roots as a defense method. These molecules could serve as novel antimicrobial agents to combat human pathogens or serve as templates for designing superior antimicrobial agents to overcome the problem of antimicrobial drug resistance in human pathogenic bacteria.

Qin Huang, Zi-Qiang Tian, Wei-Fen Li (China) Progress in the Development of Lactococcus lactis as a Mucosal Vaccine Delivery Vehicle (pp 124-134)


Invited Review: Lactococcus lactis, a food-grade, non-pathogenic, non-invasive, non-colonizing and ggenerally regarded as safeh lactic acid bacteria, is widely used in food, medicine, and husbandry industry, and it is a potential and promising candidate as a mucosal vaccine delivery vehicle (MVDV). This review describes the latest research progress of L. lactis as an MVDV and its potential improvements. Firstly, the review introduces the advantages of using L. lactis as an MVDV, emphasizing the efficient controlled protein expression and protein-targeting systems developed for production of a desired antigen. Secondly, an extensive overview is given of the progress made in improving production yield and stability of the heterologous proteins expressed in L. lactis. Thirdly, an overview is provided of the efficiency of L. lactis as MVDV for mucosal immunization. Finally, the problems limiting the use of L. lactis as MVDV are introduced and probable methods to solve them are brought forward.

Arezki Tagounits, Dominique Briane, Belén Hernández, Yves-Marie Coïc, Mahmoud Ghomi, An Cao (France) An Insight into the Use of Cationic Peptides for Plasmid DNA Delivery in Cells (pp 135-139)


Original Research Paper: In this work, we contribute an insight into the ability of cationic peptides for the delivery of plasmid DNA in cells. Although most peptides used for cellular transfection are cationic, not all of them possess this potential. Using plasmid DNA bearing reporter genes and cells of the breast cancer MDA-MB 435 line, we show at first that only peptides in an -helical structure can give high levels whereas peptides with a -strand structure cannot. Amphipathic peptides rich in lysine, namely L10K5 or L13K6, adopting both an -helical structure are able to be used for this task. Subsequently, we show that protamine, equally rich in basic arginine, but not having an -helical structure, cannot alone efficiently deliver DNA. However, it improved the transfection level by cationic liposomes, undoubtedly by a condensing effect. This enhancement in transfection by protamine was not observed using the peptide L13K6 and this peptide did not behave as protamine to enhance the transfection level of cationic liposomes.

Massimo Conese, Miriam Margherita Cortese, Sante Di Gioia, Elena Copreni (Italy) Role of Neutrophils in Internalisation and Early Clearance of Pseudomonas aeruginosa in the Mouse Lung (pp 140-143)


Original Research Paper: This study aimed to evaluate the role of neutrophils (polymorphonuclear leukocytes [PMN]) in internalisation and early clearance of Pseudomonas aeruginosa in the lung. Mice were rendered leukopenic by intraperitoneal injection of cyclophosphamide (CP) and challenged with P. aeruginosa at day four of treatment. At 24 h post-infection with a sublethal dose (1 X 104 colony forming units [cfu]), CP-treated mice showed a bacterial burden almost four orders of magnitude higher than that of control mice (P<0.05). Evaluation of the spleens showed higher numbers of bacteria in CP-treated mice than in the control mice (P=0.0004). At 4 h post-infection with a high-dose of Pseudomonas (1 X 107 cfu), although the total bacterial number was not different between the two groups, leukopenic mice showed significantly less internalised bacteria than control mice (P<0.05). Our study shows that P. aeruginosa internalisation and early clearance are greatly impaired in leukopenic mice, indicating an important role for PMN in the early defense of the lung against P. aeruginosa.

Ibrahim Hassan Garba (Nigeria), Donatien Gatsing (Cameroon), Oluwole Isaac Charles Fawole (Nigeria) Changes in Serum Manganese Concentration in Adult Patients with Acute, Uncomplicated Falciparum Malaria Infection: Potential Implications for Mitochondrial Manganese Superoxide Dismutase (MnSOD) Activity and Mitochondrial Function (pp 144-146)


Original Research Paper: Serum manganese concentration was measured in 100 adults (age range, 18-40 years) comprising of 40 males and females each presenting with acute, uncomplicated falciparum malaria infection and a control group of 20 age-matched, healthy individuals. Patient selection and pre-qualification was done by simple random sampling of individuals presenting at the Bauchi State Specialist Hospital Outpatient Department with a history of fever and malaise, and who were confirmed to be infected with the Plasmodium falciparum malaria parasite by microscopic examination of Giemsa-stained thin blood slides (parasite density in the range of 1,000-10,000 asexual forms/ml of blood). Mean serum manganese concentration in both patients and healthy individuals were compared using one way Analysis of Variance (ANOVA). The method of Least Significance Difference (LSD) was used to assess the source of difference where the ANOVA returned a P value of < 0.05. A significant decrease was found in the mean serum concentration of manganese in both the infected males and females. Mean serum manganese concentration was 198.0 } 16.45 µg/dl and 134.0 } 16.30 µg/dl in the infected males and females, respectively. These values represent a significant decrease in serum manganese (Mn) relative to their concentration in their healthy counterparts of 404.0 } 50.33 µg/dl, where P < 0.01. Mitochondria are the major intracellular sites of reactive oxygen species (ROS) production due to the activity of the mitochondrial electron transport chain. Normal mitochondrial ROS homeostasis is predominantly maintained by a Mn-dependent mitochondrial superoxide dismutase (SOD). Decreased serum Mn can lead to a compromised ROS scavenging activity by the mitochondrial SOD. In consequence, this can lead to defective mitochondrial function via ROS-induced peroxidation of mitochondrial membrane lipids and an accompanying drop in patient energy status. This usually translates symptomatically into a state of lethargy, general body weakness and malaise at great economic cost to falciparum malaria patients and malaria endemic countries.

Ibrahim Hassan Garba (Nigeria), Donatien Gatsing (Cameroon), Aliyu Rosaline, Oluwole Isaac Charles Fawole (Nigeria) Correlates between Changes in Serum Nickel Concentration, Pathogenesis and Symptomatology of Acute Falciparum Malaria Infection in Adults (pp 147-149)


Original Research Paper: Serum nickel concentration was measured in 80 adult patients (40 males and females each; age range, 18-40 years) presenting with acute, uncomplicated falciparum malaria infection and a control group of 20 age-matched, healthy individuals. Patient selection and pre-qualification was done by simple random sampling of individuals presenting at the Bauchi State Specialist Hospital Outpatient Department with a history of fever and malaise, and who were confirmed to be infected with the Plasmodium falciparum malaria parasite by microscopic examination of Giemsa-stained thin blood slides. Changes in mean serum nickel concentrations were assessed using One-Way Analysis of Variance (ANOVA). The method of Least Significant Difference (LSD) was used to further assess the source of the difference in concentrations where the p value for ANOVA was <0.05. The mean serum nickel concentration was 2.00 } 0.05 µg/dl in healthy individuals. The serum nickel concentrations were found to decrease by 50.0% in both the male and female patients, with each of them having a mean serum nickel concentration of 1.00 } 0.01 µg/dl respectively, P < 0.05. The decreased serum nickel concentration can account for some of the symptoms associated with the acute onset of human falciparum malaria infection, particularly the following: muscular discomfort, headache, limb pain, weakness, malaise and decreased serum iron since studies on nickel deprivation in animals have shown similar results. Specifically, changes in mitochondrial function because of decreased serum nickel may be associated with the observed malaise in acute falciparum malaria infection. In addition, since studies on animals have shown a perturbation in vitamin B-12 balance due to low serum nickel, the observed decrease in serum nickel during acute falciparum malaria infection can also have a profoundly negative effect on the ability of the human hematopoietic system to synthesize more red blood cells in order to counterbalance the loss due to merozoite-induced haemolysis. This is because of the immense significance of this vitamin in haemotopoiesis. Therefore, this finding suggests a potentially important role for nickel in the pathogenesis of this endemic tropical disease.

Ibrahim Hassan Garba (Nigeria), Donatien Gatsing (Cameroon), Ajibola Hauwa Salihu, Awwal Hussain Nuhu (Nigeria) Serum Copper/Zinc Concentration and Copper:Zinc Ratio in Some Selected Surgical Diseases (pp 150-152)


Original Research Paper: The trace elements copper and zinc are crucial in the process of inflammation, tissue repair and wound healing. In this study, serum Cu and Zn concentrations were measured using Flame Atomic Absorption Spectroscopy in 25 adult patients with the following surgical conditions: Benign Prostate Hyperplasia (BPH) (8), Acute Appendicitis (AAP) (5), Hernia (4), Hydrocele (4), and Typhoid Perforation (TP) (4); and a control group of 10 age-matched, healthy individuals. Mean serum Cu and Zn concentrations were 109.0 } 40.0 µg/dl and 100.0 } 20 µg/dl, respectively, and the Cu/Zn ratio was >1 in the control group. All the surgical conditions were found to have a significantly lower serum Cu and Zn concentrations at P < 0.01. Using the non-parametric method of Friedmanfs One-Way Analysis of Variance (ANOVA), the highest decrease in serum Cu concentration (89.90%) was found in patients with hydrocele. Patients with typhoid perforation had the highest decrease in serum Zn concentration (82.0%). The Cu/Zn ratio was <1 in all the surgical conditions, with the exception of typhoid perforation. The Cu/Zn ratio of <1 found in the surgical diseases reported in this study can be used as a diagnostic aid in differentiating them from malignant/lymphoproliferative diseases where the Cu/Zn ratio is >2. Furthermore, these findings are suggestive of the need for the inclusion of Cu and Zn supplementation during the post-surgical management of benign prostate hyperplasia, acute appendicitis, hernia, hydrocele and typhoid perforation.

H. Raja Naika, V. Krishna, B.G. Harish, B.M. Khadeer Ahamed, K.M. Mahadevan (India) Antimicrobial Activity of Bioactive Constituents Isolated from the Leaves of Naravelia zeylanica (L.) DC. (pp 153-159)


Original Research Paper: Two sterols compounds were isolated from the petroleum ether extract of Naravelia zeylanica leaves. The antimicrobial activity of this extract and the isolated constituents taraxerol and -sitosterol, were screened against twenty-seven clinical isolates from different infectious sources belonging to Gram-negative Pseudomonas aeruginosa and Klebsiella pneumoniae, and Gram-positive Staphylococcus aureus and five dermatitis fungi, Trichophyton rubrum, Microsporum gypseum, Tricophyton tonsurans, Microsporum audouini, and Candida albicans. The minimum inhibitory concentration of the isolated constituents was evaluated against the American Type Cell Culture (ATCC) and Microbial Type Culture Collection (MTCC) strains of the corresponding pathogenic microorganisms. The antimicrobial activity of the crude petroleum ether extract, and their isolated constituents taraxerol and -sitosterol were 150 µg/µl, 100 µg/µl and 80 µg/µl respectively. The agar wells loaded with taraxerol, -sitosterol and the petroleum ether extract exhibited a significant zone of inhibition against the clinical strains of S. aureus (23.63 } 0.09 mm). A moderate zone of inhibition was observed on the clinical strains of K. pneumoniae (21.30 } 0.15 mm) and P. aeruginosa (21.50 } 0.29 mm). The results indicated that taraxerol exhibited significant antimicrobial activity against the clinical strains of pathogenic bacteria and fungi. Taraxerol can be used as a broad-spectrum antimicrobial agent against human pathogenic bacteria and fungi. The present work was accordingly performed to characterize more potent antimicrobial metabolites from an endemic medicinal climber N. zeylanica.

Manjula Rai, Gunjan Biswas, Krishnendu Acharya (India) Antioxidant and Nitric Oxide Synthase Activation Properties of Polyporus grammocephalus Berk. (pp 160-163)


Original Research Paper: Cellular damage caused by reactive oxygen species has been implicated in several diseases and hence antioxidants have significant importance in human health. In vitro evaluation of antioxidant activities of Polyporus grammocephalus Berk. showed significant inhibition of lipid peroxidation, potent hydroxyl and 1,1-Diphenyl-2-Picrylhydrazyl (DPPH) radical scavenging activity when compared with a standard drug. IC50 values of crude, boiled and ethanolic extracts of P. grammocephalus represented 393.6 } 24.3, 300.4 } 25.43 and 62.25 } 9.67 g/ml in the case of hydroxyl radical scavenging activity, 125.10 } 34.61, 92.31 } 34.49 and 129.52 } 12.09 g/ml in DPPH radical scavenging activity, and 362.13 } 22.98, 179.33 } 27.44 and 137.2 } 22.13 g/ml for lipid peroxidation, respectively. Furthermore, crude, boiled and ethanolic extracts also increased nitric oxide production significantly, one of the important multifunctional molecules that mediate a number of diverse physiological functions (198.2 } 22.6, 112.6 } 6.70, 297.7 } 19.2 pmol/mg dry wt/h, respectively) over the control. Although all the three extracts showed antioxidant activity and NOS activation properties, the ethanolic extract was the most effective when compared with crude and boiled extracts. The present results revealed that P. grammocephalus has potent therapeutic use.

Y.S. Ravikumar, B.G. Harish, V. Krishna, K.M. Mahadevan (India) Antibacterial Activity of Stem Bark Constituents of Polyalthia cerasoides (Roxb.) Bedd. (pp 164-167)


Original Research Paper: Stem bark extract of Polyalthia cerasoides was screened against 24 clinical isolated strains from different infectious sources: Gram-negative Pseudomonas aeruginosa and Klebsiella pneumonia and Gram-positive Staphylococcus aureus. Significant minimum inhibitory zones were recorded with the ethyl acetate fraction (20.12 } 0.29, 20.00 } 0.11 and 18.35 } 0.20 mm diameter against K. pneumonia, P. aeruginosa and S. aureus, respectively) more than with the dichloromethane fraction (15.07 } 0.11, 13.52 } 0.22 and 14.67 } 0.25 mm diameter against K. pneumonia, P. aerugenosae and S. aureus, respectively). Both fractions showed activity against standard ATCC and MTCC strains. Ciprofloxacin was used as standard.

A. Vanitha, K.N. Chidambara Murthy, G. Sakthivelu, G.A. Ravishankar (India) Distribution of Carotenoids, Vitamin A in Vital Organs of Rats Fed with Dunaliella bardawil Whole Cells and Synthetic b-Carotene (pp 168-171)


Original Research Paper: Experimental rats of Wistar strain were fed with carotenoid-rich whole cells of Dunaliella bardawil and synthetic β-carotene for 14 days. The accumulation of β-carotene, lutein and vitamin A were determined in different vital organs. β-carotene and lutein significantly accumulated in the organs of rats fed with D. bardawil biomass. In rats fed with 2.5 and 5.0 g/kg b.w. D. bardawil biomass, maximum accumulation of β-carotene was observed in the liver (1.1 mg/g) while rats fed with synthetic β-carotene (50 mg/kg b.w) accumulated 1.85 µg/g β-carotene in the liver. In serum, 18.7 and 20.0 µg/l β-carotene was found in rats fed with 2.5 and 5.0 g/kg b.w. D. bardawil biomass, respectively. Lutein accumulation was exclusively found only in the groups treated with Dunaliella biomass. The vitamin A accumulation was maximum in the serum of rats fed with D. bardawil biomass (6.4 and 16.4 µg/dl with 2.5 and 5.0 g/kg b.w. D. bardawil treatment, respectively). In the same group liver retinol was found to be 2.9 and 3.52 µg/g respectively. The present study provides evidence for the accumulation of β-carotene, lutein and vitamin A in vital organs of rats when the diet is supplemented with carotenoid-rich D. bardawil biomass. This has an implication in the antioxidant status of the treated animals.

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