Volume 2 Number 1 2008

CONTENTS AND ABSTRACTS

Rosario Nicoletti, Maria Letizia Ciavatta, Elisabetta Buommino, Maria Antonietta Tufano (Italy) Antitumor Extrolites Produced by Penicillium Species (pp 1-23)

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Invited Review: Biodiversity is increasingly exploited worldwide for the finding of new pharmaceuticals. In relation to a competitive aptitude developed in many and diverse environments, microorganisms are able to produce secondary metabolites with cytotoxic and antiproliferative properties that are valuable in the perspective of antitumor drug discovery. Particularly, fungal species in the genus Penicillium represent a prolific source of biologically active extrolites that in some cases have already disclosed possible relevance for an application in cancer chemotherapy. Antiproliferative, pro-apoptotic, anti-angiogenic, anti-metastatic, DNA synthesis and cell cycle inhibitory properties of these compounds are reviewed in the present paper.

Jerry N. Abenga, Samson M. Samdi, Safiya A. Sanda (Nigeria) Sleeping Sickness: Cause and Control (pp 24-27)

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Invited Mini-Review: Sleeping sickness (Human African Trypanosomosis) is a complex and debilitating disease afflicting the marginalized communities in Sub-Saharan Africa. The disease is one of the most neglected diseases in terms of knowledge of the disease, drug development and control resulting to its persistence despite decades of attempt at vector and chemotherapeutic control. Sleeping sickness is caused by parasitic Protozoa of the genus Trypanosoma and is transmitted by bites of infected tsetse fly. The human infective species include Trypanosoma brucei gambiense and T. brucei rhodesinse which do not differ morphologically from T. brucei which cause similar disease described as “Nagana” in animals. Two forms of the disease are recognized. The chronic form described as Gambian trypanosomosis caused by T. brucei gambiense is endemic in West and Central Africa and poses difficulty in diagnosis due to typically low parasitaemia. The acute form, Rhodesian trypanosomosis caused by T. brucei rhodesiense is endemic in East Africa and parts of Central Africa. Both forms of disease are zoonotic in natural and occur in two clinical stages. The early or haematolyphatic stage is characterized by symptoms that are observed before central nervous system involvement Control of sleeping sickness is dependent on accurate diagnosis, vector control, and effective chemotherapeutic management of patients. So a treatment for early stage involves the use of pentamidine and suramin. However, in the late stage, the use of melarsoprol and Eflornithine as a treatment pair proves most effective. Presenting obstacles to effective control of sleeping sickness include insufficient surveillance, encephalopathy of arsenic compounds and implicating roles of animal reservoir hosts. Prospects for future control is therefore dependent on development of new drugs, workable national control programs, improved diagnostic tools and adopting integrated control approach which incorporates trypanosomosis control in animals.

Chua Kek Heng, Lau Tze Pheng, Foo Chui Ting, Tan Si Yen, Lian Lay Hoong (Malaysia) Genetic Polymorphisms of the TNF-α and TNF-β Genes in Malaysian SLE Patients (pp 28-33)

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Original Research Paper: A total of 100 SLE patients and 100 normal healthy controls were included in this study. Blood samples were collected and genomic DNA was extracted by using the conventional phenol-chloroform method. The DNA samples were then used to examine the association between the genetic polymorphisms of TNFs and SLE in the Malaysian population. In this study, the distribution pattern of the TNF-α -308 and TNF-β +252 genetic polymorphisms were demonstrated, in addition to their association with susceptibility to SLE. With regards to the TNF-α gene polymorphisms, the frequency of the TNF1/1 homozygote was significantly higher (χ² = 9.1912, p < 0.05) in healthy controls, while the frequency of TNF1/2 heterozygote was significantly higher (χ² = 9.1912, p < 0.05) in SLE patients. Interestingly, the TNF2/2 homozygote was not present in either SLE patients or in the healthy control group. In terms of the TNF-β gene polymorphisms, there was no significant association between the different alleles or genotypes and SLE susceptibility.

Lau Tze Pheng, Lian Lay Hoong, Tan Si Yen, Chua Kek Heng (Malaysia) VNTR Polymorphisms of the IL-1RN Gene: IL-1RN*1 Allele and the Susceptibility of SLE in the Malaysian Population (pp 34-37)

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Original Research Paper: Systemic lupus erythematosus (SLE) is a systemic autoimmune disease resulting from a defect in immunoregulation. The occurrence of this disease is mainly due to genetic, environmental and endocrine factors. Due to the role of IL-1ra in the regulation of T-cell activation, we hypothesized that its encoding gene may be associated with the susceptibility to SLE in the Malaysian population. The polymorphisms for the IL-1RN gene were analyzed in 100 SLE patients and 100 matched normal healthy controls. In this study, it was noted that the IL-1RN*1 allele was significantly associated to the susceptibility of SLE (OR = 2.667, p = 0.019). The IL-1RN*2 allele in turn, showed an inverse association (OR = 0.313, p = 0.012). Furthermore, our preliminary study also revealed the distribution pattern of genetic polymorphisms for IL-1RN gene in the Malaysian population.

Gabriel Ng, Dicky Fung, Francis Kwok, Mason Leung (China) Percutaneous Application of Panax notoginseng Extract Improves the Strength of a Healing Ligament (pp 38-40)

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Original Research Paper: This study compared the effects of Panax notoginseng (PN) extract with a composite herbal application on the healing of medial collateral ligaments (MCL) in rats. Twenty-nine rats receiving surgical tensile rupture to their right MCLs were tested. Ten rats were treated with an alcohol pad application (Group 1), 9 were treated with a composite herbal application (Group 2) and 10 were treated with an alcohol extract of PN to their right knees (Group 3). The treatments were applied percutaneously over the medial side of their right knee with adhesive plaster stabilization. The plaster and medication in all groups was changed every other day throughout the study to maintain moisture of the medication. The MCLs were harvested and tested for the biomechanical properties at 2 weeks after injury. Results revealed that the normalized ultimate tensile strength and structural stiffness of Group 3 were higher than those of Groups 1 and 2 (p=0.029 and 0.062 respectively), whereas Groups 1 and 2 were not different from one another. We conclude that PN extract application improves the mechanical strength of repairing MCLs at 2 weeks after injury.

Ganiyu Oboh (Nigeria) Polyphenol Extracts from Hyptis suaveolens Leaves Inhibit Fe²⁺-induced Lipid Peroxidation in Brain (pp 41-46)

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Original Research Paper: The present study seeks to compare the protective properties of free and bound polyphenols from Hyptis suaveolens leaves (a commonly used spice) on Fe²⁺-induced lipid peroxidation in rat’s brain in vitro. The free soluble polyphenols were extracted with 80% acetone, while the bound polyphenols were extracted with ethyl acetate from alkaline and acid hydrolyzed residue from free soluble extract. The inhibitory effect of the polyphenol extracts on Fe²⁺ (25µM)-induced lipid peroxidation in rat’s brain was determined. The total phenol content and antioxidant properties (1,1-diphenyl -2-picrylhydrazyl (DPPH) free radical scavenging ability, reducing power and Fe (II) chelating ability) of the extracts were determined. The results of the study revealed that the leaf contains 3.88 mg/g total phenol [2.94 (free), 0.94 (bound)]. Incubation of the brain in the presence of Fe (II) caused a significant increase (P<0.05) in the malondialdehyde (MDA) content of the brain (256%). However, the polyphenol extracts (0.4–1.6 µg/ml) caused a dose-dependent significant decrease (P<0.05) in the MDA contents in the brain. The free soluble polyphenol extracts had a significantly higher (P<0.05) inhibitory effect on the Fe (II)-induced lipid peroxidation in brain and higher antioxidant properties. Therefore, the higher antioxidant properties of free soluble polyphenols (which are more) from H. suaveolens leaves could have been responsible for its high protection against Fe (II)-induced lipid in brain – in vitro.

Kartick Chandra Pramanik, Sanchita Ghosh, Dilip Kumar Midya, Tapan Kumar Chatterjee (India) Antitumor Activity and Antioxidant Role of Tissue Cultured Pluchea indica Root against Ehrlich Ascites Carcinoma in Swiss Albino Mice (pp 47-50)

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Original Research Paper: One of the major achievements of medical science has been the control and management of infectious diseases. The present study was designed to evaluate the antitumor effect and antioxidant role of methanolic root extract of tissue cultured Pluchea indica. Antitumor activity and antioxidant status of this extract (100 and 300 mg/kg) were evaluated against Ehrlich Ascites Carcinoma (EAC) cells in mice. After 24 h of tumor inoculation, the root extract was administered orally daily for 14 days. After administered of the last dose followed by 18 h fasting, mice were then sacrificed for observation of anti-tumor activity. The effect of methanolic extract of P. indica (MEPI) on the growth of transplantable murine tumor and life span of EAC bearing hosts were estimated. Simultaneously the hematological values and liver biochemical parameters (lipid peroxidation, antioxidant enzymes) were estimated in treated animals. MEPI decreased mice weight, tumor volume, viable cell count and amounted to 19.25 g, 1.87 ml, and 24.00 × 10⁶ cells/ml, respectively when compared to EAC control. MEPI also showed an increase in the non-viable cell count (55.25 × 10⁶ cells/ml) and mean survival time of 26.50 days thereby increasing the life span by 62.27% more than EAC tumor-bearing mice. The hematological profile reverted to more or less normal levels in extract-treated mice. Treatment with MEPI decreases the levels of lipid peroxidation and increases the levels of glutathione, super oxide dismutase and catalase. It was revealed from the study that the tissue cultured P. indica root extract possesses potent antitumor and antioxidant activities.

Sabuj Sahoo, Prasana Kumar Panda, Satyaranjan Mishra, Anindita Nayak, Sashi Kanta Dash, Poluri Ellaiah (India) Bioparametric Investigation for the Production of Hyaluronidase by Streptococcus mitis MTCC *2695 (pp 51-54)

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Original Research Paper: The effect of some physical and nutritional parameters were studied for the optimum production of extracellular enzyme hyaluronidase employing Streptococcus mitis MTCC *2695 by submerged fermentation. The effects of initial pH, incubation temperature, time, inoculum concentration and age of inoculum were studied. Maximum enzymatic activity was observed at initial medium pH 5.8, at 37°C, within 48 h and with 6% inoculum. The effect of different carbon and nitrogen sources and antibiotics were studied. Sucrose and ammonium chloride showed the highest enzymatic activity among different carbon and nitrogen sources studied. The antibiotic clarithromycin showed strong inhibitory effect on hyaluronidase production.

Wei-lin Li, Ju-lan Wu, Bing-ru Ren, Jian Chen, Han-qing Zhang (China) Pharmacological Action of Some Chemical Constituents from Ilex cornuta Lindl. ex Paxt. for Cardiac Diseases (pp 55-58)

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Original Research Paper: Fourteen compounds were isolated from the dried leaves of Ilex cornuta Lindl. ex Paxt. and were identified based on chemical and spectral evidence, and for which pharmacological tests of compounds 3,4-dihydroxyl cinnamic acid, daucostorol and gouguside 4 [3-β-O-(β-D-glucopyranosyl-α-L-arabinopyranosyl)-pomolic acid (28→1)-β-D-glucopyranosyl ester] were carried out to evaluate the effect for cardiac diseases. The results showed that 3,4-dihydroxyl cinnamic acid and daucostorol did not give protection to mice against hypoxia, ventricular fibrillation caused by chloroform and myocardial ischemia induced by pituitrin, Gouguside 4 performed similarly as the former two compounds but protected rats against pituitrin-induced myocardial ischemia. 3,4-dihydroxyl cinnamic acid and daucostorol had no influence on the cardiac rate of apo-cardiac muscle, crown sphygmo-flow and contractility of cardiac muscle of guinea pigs either. Gouguside 4 did not influence the cardiac rate of apo-cardiac muscle, crown sphygmo-flow, but decreased contractility of cardiac muscle of guinea pigs.

Nathalia D. Prihoda, Olga V. Arjanova, Lyudmila V. Yurchenko, Nina I. Sokolenko, Lyudmila A. Vihrova, Volodymyr S. Pylypchuk, Galyna A. Kutsyna (Ukraine) Adjunct Immunotherapy of Tuberculosis in Drug-Resistant TB and TB/HIV Co-Infected Patients (pp 59-64)

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Original Research Paper: Open-label, salvage anti-tuberculosis therapy (ATT) combined with DZHERELO (IMMUNOXEL), SVITANOK, and LIZORM – over-the-counter immunomodulators from medicinal plants – was conducted in 20 Ukrainian patients, comprising seven who had HIV co-infection. Except five patients with HIV, all other individuals had multidrug-resistant TB (MDR-TB) including 7 (35%) patients with XDR-TB. Patients hospitalized in our TB dispensary were treated under directly observed therapy (DOT) until repeated negative culture conversion and recuperation from radiological and clinical symptoms. The average duration of therapy was 16.2 ± 5.2 weeks (range 10.6-30.3; median 16). The mean time to bacterial clearance was 4.4 ± 1.8 weeks (range 1.3-8.9, median 4.3). All patients (95%), except one, gained weight, ranging between 3-17 kg with average 8.7 kg (P=0.000009). The liver function tests revealed that the level of total bilirubin had decreased from 15.5 to 11.6 μmol/L (P=0.009). Alanine transaminase (ALT) declined from elevated 53.1 IU/L to normal 30.4 IU/L level (P=0.001). Hemoglobin levels increased from 103.2 to 117.3 g/L (P=0.00005). Inflammation-associated, elevated leukocyte counts returned back to normal from 8.9 to 6.9 × 10⁹ cells/L (P=0.003). Patients improved clinically and radiologically and were hence discharged from the hospital. These findings support prior trials indicating clinical benefit of adding immunomodulators to TB treatment regimens. The combination of ATT with botanical preparations enhances the clinical efficacy of DOT and is safe and beneficial even to patients with poor prognosis due to drug resistance and/or co-infection with HIV.

Balaraman Ganesan, Rangasamy Anandan, Rangasamy Rajesh (India) Protective Effect of Betaine on Changes in Lipid Profile, Lipoproteins and Fatty Acid Composition in Experimentally Induced Myocardial Infarction in Wistar Rats (pp 65-69)

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Original Research Paper: Myocardial infarction (MI) is one of the most common manifestations of cardiovascular disease. In recent years, accumulating evidence has indicated that the incidence and progression of cardiovascular disease may, to some extent, be modified by dietary means. In the present study, we investigated the protective effect of betaine, a potent lipotropic molecule, on changes in lipid profile and fatty acid composition in isoprenaline-induced myocardial infarction in rats, an animal model of myocardial infarction in man. Oral administration of betaine (250 mg/kg body weight/day for a period of 30 days) significantly reduced the isoprenaline-induced hyperlipidemic abnormalities noted in the levels of lipoprotein, cholesterol, triglycerides and free fatty acids in plasma and heart tissue. Pretreatment with betaine significantly attenuated isoprenaline-induced phospholipid depletion in the heart tissue and preserved the myocardial fatty acid composition at levels comparable to that of control rats. It also significantly counteracted the isoprenaline-mediated lipid peroxidation and maintained the level of non-enzymatic antioxidant, reduced glutathione (GSH) at near normal. The results of the present study indicated that the overall cardioprotective effect of betaine is probably related to an inhibition of lipid accumulation by its hypolipidemic properties or to a counteraction of free radicals by its antioxidant nature.

Muthuswamy Umamaheswari, Tapan Kumar Chatterjee (India) Effect of the Fractions of Coccinia grandis on Naphthalene-induced Cataractogenesis in Rats (pp 70-74)

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Original Research Paper: Cataract, an opacity of the lens, is one of the major causes of blindness worldwide. The leaves of Coccinia grandis L. Voigt belonging to the family Cucurbitaceae are used in Indian traditional medicine for the treatment of gout, rheumatism, jaundice, eye infections, bronchitis, fever, skin eruptions, wounds, etc. The petroleum ether, chloroform, ethyl acetate, and residual fractions of the hydromethanolic extract of the leaves of C. grandis at a dose of 200 mg/kg b.w. were given orally to Wistar albino rats simultaneously with naphthalene (1 g/kg) for 28 days. Vitamin E (50 mg/kg) was used as the standard. Cataract progression due to naphthalene feeding was monitored using an ophthalmoscope and classified into 5 stages. At the end of the experiment, levels of malondialdehyde, lipid hydroperoxides, carbonyl and sulfhydryl content, enzymatic and non-enzymatic antioxidants in lens homogenate were measured. Administration of naphthalene produced a mature cataract and an increase in the opacity index. In addition, there was a significant increase in lipid peroxidation and protein carbonyl content and a decrease in protein sulfhydryl content and antioxidant enzymes when compared to healthy controls. Ophthalmoscopic observations indicated that simultaneous administration of the fractions delayed the onset and maturation of cataract. All the fractions (except the residual fraction) prevented the peroxidative damage caused by naphthalene, which is evidenced from the improved antioxidant potential. The effect produced by the chloroform fraction was almost comparable with the vitamin E-treated group. The leaves of C. grandis protected the lens against naphthalene damage which may be due to its antioxidant activity.