Journal of Pharmacology and Toxicology

No Issue Number

• Anti-arthritic Effects of an Ethanolic Extract of <I>Capparis erythrocarpos</I> Isert Roots in Freund’s Adjuvant-induced Arthritis in Rats
  Capparis erythrocarpos (Capparaceae) is a medicinal plant used traditionally in Ghana and other parts of Africa for the management of various inflammatory and pain conditions without any scientific validation. The aim of this study, therefore was to provide scientific evidence for the use of this plant as an anti-arthritic agent using the Freund’s Adjuvant-induced arthritis in rats, a chronic inflammatory model which mimics rheumatoid arthritis in humans. Arthritis was induced by injection of Complete Freund’s Adjuvant into the right paw of Sprague-Dawley rats and paw volume was measured by water displacement plethysmography. Dexamethasone and methotrexate were used as reference drugs. The results obtained show that treatment with the extract (30 mg kg ^-1 ; p.o.) significantly suppressed adjuvant-induced arthritis with maximal inhibitions of 34.19±15.73% and also significantly prevented the spread of arthritis from the ipsilateral to the contralateral paw. Higher doses of the extract (100 and 300 mg kg ^-1 ; p.o.) did not show significant inhibition of arthritis. Methotrexate (0.1-1.0 mg kg ^-1 ) and dexamethasone (0.3-3 mg kg ^-1 ) significantly and dose-dependently inhibited polyarthritis and completely prevented the spread of arthritis to the contralateral paws. Adjuvant-induced arthritis was ameliorated by the combined effect of C. erythrocarpos (100 mg kg ^-1 ; p.o.) and dexamethasone (1 mg kg ^-1 ; i.p.) as well as C. erythrocarpos (100 mg kg ^-1 ; p.o.) and methotrexate (0.3 mg kg ^-1 ; i.p.). From the results, C. erythrocarpos had anti-arthritic effect and the effect shown is comparable to that of methotrexate. This provides a validation for the traditional use of the plant in managing rheumatoid arthritis.
  
• Hepatoprotective Influence of Vitamin C on Thioacetamide-induced Liver Cirrhosis in Wistar Male Rats
  Liver cirrhosis is a worldwide health problem and one of the most prevalent chronic diseases. Cirrhosis is scarring of the liver that involves the formation of fibrous (scar) tissue associated with the destruction of the normal architecture of the organ. Hence, the investigation for an efficient hepatoprotective drug is an urgent need. In the present study an attempt was made to investigate whether vitamin C could prevent liver cirrhosis induced by thioacetamide (TAA) in Wistar male rats. The chronic administration of TAA for a period of 10 weeks increased the levels of serum total bilirubin, triglycerides, cholesterol, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), creatine kinase (CK) and lactate dehydrogenase (LDH), while the levels of glucose, total protein, albumin and the values of red blood corpuscles (RBC) count, hemoglobin (Hb) concentration, hematocrit (Hct) and white blood corpuscles (WBC) count were statistically decreased. Moreover, the administration of TAA induced hepatic nodular transformations and the parenchyma nodules surrounded by fibrous septae. TAA administration induced centrilobular necrosis, hepatic cells surrounding central vein showed various degenerative changes like cloudy swelling, hydropic degeneration and necrosis with loss of nucleus. The administration of vitamin C after TAA intoxication led to decrease the severe biochemical, hematological and histopathological changes. But more overt protections were observed in rats supplemented with vitamin C before TAA exposure. The present findings suggest that pretreatment with vitamin C could be more useful for the prevention of hepatic cirrhosis induced by TAA in rats.
  
• Pancreatic Gene Expression Altered Following Dietary Exposure to 2-Aminoanthracene: Links to Diabetogenic Activity
  The mutagen 2-aminoanthracene (2-AA) is an aromatic amine or arylamine, which belongs to a class of polycyclic aromatic hydrocarbons. 2-AA is used in the manufacturing of a wide variety of chemicals, drugs, dyes and polymers. Non-occupational sources include tobacco smoking and cooked foods. The goal of this study is to evaluate pancreatic gene expression patterns in Fischer-344 (F-344) male rats exposed to 2-AA. As a first step the effects of 2-aminoanthracene exposure on the pancreas with particular interest in genes that relate to insulin and insulin metabolism. To achieve this goal, twenty-four post-weaning, 3-4 week old F-344 male rats were exposed to 0 mg kg ^-1 -diet (control), 50 mg kg ^-1 -diet (low dose), 75 mg kg ^-1 -diet (medium dose) and 100 mg kg ^-1 -diet (high dose) 2-AA for 14 and 28 days followed by analysis of the pancreas for broad gene expression changes. Results obtained from our study suggest most of the mRNA transcripts that were differentially expressed are involved in energy metabolism in the pancreas, protein digestion and some that play an active role in pancreatitis and pancreatic cancer. Some of these genes include: insulin, colipase pancreatic, carboxypeptidase, chymotrypsinogen B1 and chymotrypsin C (caldecrin). These findings seem to point to the role of 2-AA in the dysregulation of several pancreatic genes that regulate lipid and protein metabolism in a way that involves a feedback mechanism which may ultimately lead to insulin resistance and tissue autolysis. Quantitative PCR determination of fold changes in selected genes show similar trends to global expression determined via microarray analyses.
  
• Preventive Effect of <I>Bridelia ferruginea</I> Against High-fructose Diet Induced Glucose Intolerance, Oxidative Stress and Hyperlipidemia in Male Wistar Rats
  The root of B. ferruginea is traditionnally used as a treatment for type 2 diabetes. The present study was investigated to evaluate the preventive effect of B. ferruginea on some markers of metabolic syndrome in type 2 diabetes (hyperlipidemia, glucose intolerance, obesity and oxidative stress) induced by high fructose and fat diet in male Wistar rat. The rats received fructose diet (10 mL kg ^-1 per day) during 42 days; at the 15th day to the 42nd day 15 min before, they received distilled water for high fructose diet group, metformine 100 mg kg ^-1 per day or extract 125 and 250 mg kg ^-1 per day for treatment group. The control group received only distilled water during the experiment. After 6 weeks of experiment, fasting blood glucose, liver MDA level, body weight gain, intra abdominal grease, serum triglyceride (TG) and total cholesterol levels in treated groups were significant lower than that of high- fructose diet group. However, rats in treated group were not found to have a significant change of blood HDL Cholesterol level. In the oral glucose tolerance test, rats in treated group had a significantly reduced blood glucose concentration during 180 min after glucose load, indicating that B. ferruginea root improved glucose tolerance. In conclusion, our plant can prevent metabolic syndrome induced by high fructose diet.
  
• Hypoglycemic Effect, Biochemical and Histological Changes of <I>Spondias mombin</I> Linn. and <I>Parinari polyandra</I> Benth. Seeds Ethanolic Extracts in Alloxan-induced Diabetic Rats
  The aim of this study was to evaluate the individual and synergistic hypoglycaemic and biochemical effects of the ethanolic extracts of seeds of Parinari polyandra and Spondias mombin in alloxan-induced diabetic rats. The ethanolic extracts of the seeds of Parinari polyandra and Spondias mombin were obtained by soxhlet extraction and administered to non-diabetic and alloxan-induced diabetic albino rats. Parameters including blood glucose, alanine aminotransferase (ALT), aspartate transaminase (AST), lipid peroxidation, triglycerides, cholesterol, glutathione and total protein were checked using standard test kits and methods after administration of the extracts. Histological changes in the liver of the animal were also examined. The results obtained revealed that alanine aminotransferase (ALT), aspartate transaminase (AST), lipid peroxidation, triglycerides, cholesterol and glutathione did not change significantly (p≤0.05) in the animals treated with the plant extracts. Glucose and total protein levels were significantly reduced (p≤0.05) in the animals treated with the plant extracts. The histological changes showed the presence of fatty cells in the liver of alloxan-induced diabetic control and non diabetic rats administered both Parinari polyandra and Spondias mombin extracts. The implications of the results obtained especially reduction of glucose by Parinari polyandra and Spondias mombin is their potential use in management of diabetes and apparent effects on the liver when administered together.
  
• Acute Oral Toxicity Study of <I>Pluchea arguta </I>Boiss Extract in Mice
  Acute oral toxicity of methanol extract of Pluchea arguta Boiss was evaluated in Swiss albino mice of both sexes. In this study mice were administered orally with dosages of 1000, 3000 and 6000 mg kg ^-1 b.wt. of methanol extract of P. arguta extract. Mortality, signs of toxicity, body weight, food and water consumption, haematological and gross behaviour was observed for 7 days post treatment of P. arguta extract. No mortality, signs of toxicity and abnormalities in gross behaviour were observed. In addition, no significant differences were noticed in the body and organ weights between the control and treated groups of both sexes. The methanol extract of P. arguta is nontoxic and safe by oral intake.
  
• Pharmacological and Toxicological Properties of Leaf Extracts of <I>Kingelia africana</I> (Bignoniaceae)
  Leaf extracts of Kingelia africana were evaluated for wound healing, antibacterial, toxicological and chemical properties. Antibacterial activity was done using hole-in-plate bioassay, wound healing by circular incision, toxicological and chemical properties were evaluated using standard methods. The results show a more rapid wound healing at all the hydromethanolic concentrations employed than 90 mg mL ^-1 of procaine penicillin on the 4, 7, 10, 13, 16 and 19th day. Exudation was more prominent in control and antibiotic treated groups compared to other groups on day 2 of wounding. Clinical features revealed redness, exudation, scab formation and other changes. The aqueous and organic solvent leaf extracts exhibited significant (p<0.05) antibacterial activity against Pseudomonas aeruginosa, Staphylococcus aureus and Escherichia coli at concentrations ranging from 30 to 120 mg mL ^-1 . Most of the hepatorenal indices were significantly (p<0.05) increased at doses of 2000 to 4000 mg kg ^-1 indicating compromised functions of these organs. The lethal dose (LD ₅₀ ) of the leaf extract was greater than 3000 mg kg ^-1 . Alkaloids (9.80±0.20), tannins (22.80±0.05), saponins (8.85±0.50), flavonoids (7.80±1.00% w/v), glycosides, saponin glycosides, steroids and anthraquinones were detected. Low values of sodium (6.5±0.01) potassium (3.1±0.01), magnesium (0.126±0.03), phosphorus (2.04±0.04) and calcium (0.108±0.01 mg%) were observed. The results show that leaves extracts of K. africana could be cautiously used and also provide support for the traditional use of the plant in treating bacterial diseases and wound healing due to its chemical constituents.
  
• Ameliorating Effect of Vitamin E on Testicular Toxicity Induced by Endosulphan in <I>Capra hircus in vitro</I>
  During the present investigation ameliorating effect of vitamin E on endosulphan induced testicular toxicity has been analyzed in Capra hircus in vitro . Vitamin E exhibited the protective role against the damage induced by endosulphan in the testicular tissue. Small pieces (approximately 1 mm ³ ) of testicular tissue were divided into three groups (One control and two experimental groups). One experimental group was treated with 100 nmol mL ^-1 endosulphan concentration and another experimental group was treated with 100 nmol mL ^-1 endosulphan and supplemented with 100 μmol L ^-1 concentration of vitamin E (α-Tocopherol). Harvesting of the testicular tissue was carried out after 1, 4 and 8 h of exposure durations in vitro . Hyalinization and fragmentation was observed in the endosulphan treated group. Chromolysis was observed in spermatogonia, Sertoli cells and spermatids. As the exposure duration enhanced from 4 to 8 h there was elevation in number of pycnotic nuclei, fragmented nuclei, chromolysis of germ cells and somatic cells present in the testis. Endosulphan exposure induced the number of atretic spermatogonia from 24% in control group to 68% after 1 h, from 30 to 76% after 4 h and from 36 to 84% after 8 h of exposure duration. In the experimental group treated with endosulphan and supplemented with vitamin E there was decline in number of pycnotic nuclei, fragmented nuclei and chromolysis as compared with the endosulphan exposed group. There was decline in atretic spermatogonia from 68 to 36% at 1 h, from 76 to 44% after 4 h and from 84 to 58% after 8 h of supplementation duration.
  
• <I>In vivo</I> Study on Lead, Cadmium and Zinc Supplementations on Spermatogenesis in Albino Rats
  This study was designed to elucidate the mechanisms accounting for disruption of the normal spermatogenesis in the testis, exposed to various levels of cadmium (Cd), lead (Pb) and zinc (Zn). Forty two mature male Albino rats, were divided into six groups; group 1 treated with 100 mg Cd kg ^-1 diet, group 2 treated with 5 mg Pb kg ^-1 diet, group 3 with 50 mg Zn kg ^-1 diet, group 4 treated with mixture of 5 mg Pb +50 mg Cd kg ^-1 diet, group 5 treated with 50 mg Cd + 25 mg Zn kg ^-1 diet and group 6 treated with 5 mg Pb +25 mg Zn kg ^-1 diet for three month. Group 7 was kept as control. Significant increased (p<0.05), of both blood Cd and Pb with loss of both weight and hair associated with testicular enlargement in rats dosed with Cd and/or Pb in the diet. As a consequence these groups showed blockage of spermatogenesis at seminiferous tubules level, maturation arrest and proliferation of the sertoli cells. Where as the group treated with Zn, showed increased weight and increased number of germs cells and developing spermatide in the testicular level. The combined diet of Cd with Pb in one dose exacerbated the toxic action of these elements. While mixing of Zn with Cd and Pb reduced the toxicity of these elements and their effects on development of the germ cell and the proliferation of the sertoli cells.
  

  No Issue Number

• Impact of Curacron Toxicity on Lactate Dehydrogenase in the Serum of the Fish <I>Cyprinus carpio</I>
  The experiment was conducted on fish, Cyprinus carpio to study the effect of curacron on serum biomarker (LDH). Curacron is a organophosphate pesticide and is used by the farmers to protect their crops. This pesticide reaches to the aquatic ecosystem by many ways and affects the aquatic fauna. LC ₅₀ of Curacron for Cyprinus carpio has been calculated by the log-dose/probit regression line method and recorded as 0.38 ppm at 96 h. Three sub-lethal concentrations (0.1, 0.01 mL and 0.001 ml L ^-1 ) were selected to expose the fish for 1, 7, 14 and 21 days. Changes in enzyme activity were observed with all concentrations and exposure period. Lactate concentrations were significantly lower in the experimental group, compared with the control group. The above results of blood plasma profile indicate a marked cytotoxic and hepatotoxic effect of curacron in fishes.
  
• Establishing the Principle of Herbal Therapy for Antiurolithiatic Activity: A Review
  A wide range of plants and plant-derived products are used in folk medicine for the treatment of urolithiasis as a prophylactic agent or as curative agent. Most of them found to be effective, but still the complete mechanism of action of these herbal drugs remains to be unclear. In present review we are discussing the various mechanism of action through which phytotheraeupatic agents exert their antiurolithiatic effect. Unlike allopathic medicines which targets only one aspect of urolithiatic pathophysiology, most of plant based therapy have been shown to be effective at different stages of stone pathophysiology. Currently known herbal drugs exert their antilithogenic properties by altering the ionic composition of urine viz.; decreasing the calcium and oxalate ion concentration or increasing magnesium and citrate excretion. Most of these remedies also express diuretic activity or lithotriptic activity. Some of the herbal drugs reported to disaggregate of mucoproteins, which are actually binds the crystal to the renal cells. Some medicinal plants contain chemical compounds like Glycosaminoglycans (GAGs) which themselves possess an inhibitory effect in the crystallization of calcium oxalate. Antioxidant constituents of the plants also help in ameliorating the crystal/oxalate induced renal cell injury. Thus, antiurolithiatic activity of plants or herbal formulation may be due to synergism of their diuretic activity, crystallization inhibition along with antioxidant activity.
  
• Antimicrobial Activity of Essential Oil and Extracts of <I>Gongronema latifolium</I> Decne on Bacterial Isolates from Blood Stream of HIV Infected Patients
  The essential oil as well as aqueous and ethanolic extracts of Gongronema latifolium leaves was evaluated for antimicrobial activity against bacteria isolated from blood streams of HIV patients in Lagos. Using agar diffusion method, the essential oil and the extracts showed moderate inhibitory activity against all the Stphylococcus sp., Escherichia coli , Shigella sp., Salmonella sp., Klebsiella pneumonia , Pseudomonas aeruginosa , Onchrobactrum anthropi and Candida albicans . The zones of inhibition values recorded were comparable to control antibiotic ampicillin but less than that of Ciprofloxacin and Chloramphenicol. The MIC for essential oil ranged between 5-40 μg mL ^-1 , while MBC also ranged between 5-40 μg mL ^-1 , the MIC and MBC for ethanol extract ranged between 3.125-12.5 mg mL ^-1 and 3.125-25.0 mg mL ^-1 , while aqueous extract MIC range between 6.25-25.0 mg mL ^-1 and MBC also ranged between 6.25-25.0 mg mL ^-1 , respectively. Extracts of Gongronema latifolium may be useful in ethnomedicine and in the treatment of blood stream infections in HIV patients. Essential oil from Gongronema latifolium leaves (Endl.) Decne was obtained by hydrodistillation and analyzed using Gas Chromatography/Mass Spectrophotometry (GC-MS). The oil was dominated by linear aliphatic compounds (27.06%),unsaturated fatty acids which was characterized by high percentage of Phthalic acid (18.61%), oleic acids (5.2%), arachidic acid (2.34%) and fumaric acid (2.22%). Monoterpenes including camphor, β-Cymene and phytol.
  
• Diversity of Bacteria and Fungi in the Gut and Cast of the Tropical Earthworm <I>Glyphodrillus tuberosus</I> Isolated from Conventional and Organic Rice Fields
  A comparative study of the bacterial and fungal diversity in the gut and cast of Glyphodrillus tuberosus , isolated from organic and conventional rice fields in Orissa state, India was done in different seasons for a period of two years from 2007 to 2009. Isolation of the strains was done by serial dilution method on incubation of the inoculated plates at 28°C for 72 h for fungi and at 37°C for 24 h for bacteria. Isolated strains were identified as Bacillus sp., Pseudomonas sp. , Staphylococcus sp ., Bacillus subtilis, Bacillus lentus, Azotobacter sp ., Micrococcus sp ., Flavobacterium sp ., Acinetobacter sp ., Brevibacterium sp. and Thiobacillus sp., while the molds identified were Aspergillus niger, Aspergillus flavus , Fusarium sp ., Penicillium sp. and Rhizopus sp. Microbial load was observed significantly higher (p<0.01) in gut sections and cast of the worm than in un-ingested soils. The earthworm was found to constitute a microhabitat enriched in microbes capable of growth and activity. Numbers of bacteria and fungi were observed significantly higher (p<0.01) in the gut section, worm cast and undigested soil of organic rice field in comparison to conventional one. Soil pH and percent moisture did not show significant differences between the two management systems. Season wise comparison showed that irrespective of farming systems bacterial and fungal load were maximum in rainy season than in the other and was attributed to high soil moisture content, which is an important limiting factor in tropical soil.
  
• Hematologic and Hepatic Enzyme Alterations Associated with Acute Administration of Antiretroviral Drugs
  The aim of this study was to assess the effects of short-term administration of some antiretroviral drugs on hematological and hepatic parameters in albino rats. The rats were treated with 0.43, 0.43, 0.27 and 0.21 mg kg ^-1 of Efavirenz, Abacavir, SNP 40 and Lamivudine respectively, for seven days. The control group received normal saline. On the eighth day, the rats were sacrificed; blood and liver were collected for White Blood Cell Count (WBC), Packed Cell Volume (PCV), Aspartate aminotransferase (AST), Alanine aminotransferase (ALT) and Alkaline phosphatase (ALP) analysis. All the drugs showed significant increase (p<0.05) in %WBC (43.0, 42.6, 52.3 and 37.4%) for Efavirenz, Abacavir, SNP 40 and Lamivudine respectively. Abacavir, SNP 40 and Lamivudine significantly decreased (p<0.05) ALP by 66.67, 84.75 and 56.24%, respectively while Efavirenz and Abacavir caused significant increase and decrease (p<0.05) in AST by 9.09 and 16.36% respectively. Efavirenz, Abacavir and Lamivudine caused significant increase (p<0.05) in ALT by 321.6, 497.6 and 177%, respectively. The drugs significantly increased the immunity of the animals and Efavirenz, Lamivudine and Abacavir caused hepatic damage. The clinical implication of our findings is that hepatoprotective agents should be included in the treatment regimen when administering antiretroviral drugs such as Efavirenz, Lamivudine and Abacavir.
  
• Carbon Tetrachloride-induced Hepatotoxicity and Nephrotoxicity in Rats: Protective Role of Vitamin C
  Glutathione plays an important role in the detoxification of most toxic agents. This study was planned to investigate the protective effect of vitamin C on chronic and acute models of carbon tetrachloride (CCl ₄ )-induced oxidative stress and changes of the glutathione concentration (GSH) in the liver and kidney of Wistar rats. The administration of vitamin C (Vit. C) to the rats (100 mg/1 kg) with intraperitoneal injection of CCl ₄ at dose level of 0.2 mL kg ^-1 (twice a week for 3 months) or 1 mL kg ^-1 (single dose) significantly reduced the elevated plasma levels of aminotransferases, alkaline phosphatase, blood hydroperoxide, malondialdehyde in liver and kidney and blood creatinine. Vit. C antagonized the decrease of GSH level caused by CCl ₄ . In CCl ₄ (chronic dose) + Vit. C group, plasma cholesterol and triglycerides levels were significantly decreased, while high density lipoprotein and protein concentrations were significantly increased, when compared to CCl ₄ group. The treatment of rats with CCl ₄ as a single dose (1 mL kg ^-1 ) has no significant influence on lipids. Plasma urea and uric acid levels of CCl ₄ +Vit. C group were significantly increased as compared to CCl ₄ group. These results showed that vitamin C had a protective effect on hepatotoxicity and renal toxicity caused by CCl ₄ induced oxidative stress via its antioxidative property, reducing the lipid peroxidation and normalizing the glutathione level with improved the alterations in the biochemical markers. Moreover, Vit. C showed hypolipidemic effect in CCl ₄ -treated rats.
  
• Effects of Selected <I>Boesenbergia </I>Species on the Proliferation of Several Cancer Cell Lines
  The aim of this research was to determine the potential of Boesenbergia species collected from Sabah rainforest as anticancer remedy . This research was done to Boesenbergia rotunda, B. pulchella, B. pulchella var attenuata and B. armeniaca crude extracts on the in vitro proliferation of hormone-dependent breast cancer (MCF-7), non-hormone dependent breast cancer (MDA-MB-231), ovarian cancer (CaOV ₃ ), colon cancer (HT-29) and cervix cancer (Hela) cell lines. The effects of the four Boesenbergia species (methanol extracts of leaves, stem and rhizome part) on the proliferation of MCF-7, MDA-MB-231, CaOV ₃ , HT-29 and Hela cell lines were measured using (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) MTT assay. The crude extracts with IC ₅₀ value less than 100 μg mL ^-1 were subjected to cell cycle analysis by using flow cytometry for DNA content determination. B. rotunda as positive control showed significant inhibitions towards all the cancer cell lines tested with IC ₅₀ ranging from 51.0±0.01 to 71.0±1.41 μg mL ^-1 . The remaining Boesenbergia species only showed positive cytotoxicity activities against MCF-7 cell lines especially B. pulchella var attenuata with IC ₅₀ value 93.0±2.83 μg mL ^-1 and B. armeniaca with 94.5±0.71 μg mL ^-1 . In cell cycle analysis, B. rotunda crude extract arrested cell at sub-G1 phase while B. pulchella var attenuata arrested cell at G ₂ /M phase. From this study, it can be concluded that only B. pulchella var attenuata and B. armeniaca were effective against cellular proliferations of MCF-7. However, both species were not as effective as B. rotunda .
  
• Coenzyme Q10 Ameliorates Statin-related Myotoxicity: A Biochemical and Histological Study
  Statins are the mainstay in the pharmacological management of dyslipidemia. They may also have anti-inflammatory, anti-proliferative and anti-oxidative effects. Since they are widely prescribed, their safety remains an issue of concern. The major untoward effect of statins is myotoxicity, which ranges from mild to severe. In addition to inhibiting endogenous cholesterol synthesis, however, statins decrease coenzyme Q10 (CoQ10) synthesis, the decrease of which may be implicated in statin myotoxicity. Hence, the present study evaluated the effect of CoQ10 supplementation against simvastatin and atorvastatin induced myotoxicity, measuring creatinine phosphokinase (CPK), lactate dehydrogenase (LDH), myoglobin as well as K, creatinine and CoQ10 level along with histopathological determinants. Sprague-dawley adult male albino rats were orally administered simvastatin or atorvastatin (20, 80 mg day ^-1 ) for 3 months with concurrent oral CoQ10 (100 mg day ^-1 ) administration. Simvastatin or atorvastatin in the higher dose used caused significant elevation of CPK, LDH, K and myoglobin, depletion of CoQ10 level along with histological muscle damage. This was more evident with atorvastatin with respect to simvastatin. Concurrent administration of CoQ10 showed significant modulation of CPK, LDH, K and myoglobin concomitant to restoration of depleted CoQ10 level and improvement in histopathological muscle findings. Present findings demonstrate the protective effect of CoQ10 against myotoxicity of simvastatins and atorvastatin suggesting its use to avoid poor adherence to statin treatment and increase clinical benefit.
  
• Evaluation of the Toxicity of Manihot esculenta on Wistar Rats after Traditional Sudanese Processing
  In Sudan and other countries, Manihot esculenta roots (cassava) consumed mainly as flour after a traditional processing which we are suggesting that it's not enough to eliminate all cyanogenic glycoside (toxic compound). This study was carried out to evaluate the aqueous and methanolic extracts toxicity of Manihot esculenta (cassava) tubercular roots on Wistar rats after traditional processing in two weeks consumption. The plant was peeled and dried after that it was extracted using methanol and water. Wistar rats were allotted at random to five groups, each of 6 rats; four groups were given their designated dose of the extracts of both aqueous and methanol in two different dose orally which was 75 and 300 mg kg ^-1 , the fifth group was control. The mortality and weight gain, serobiochemical and hematological parameters were recorded in addition to pathological changes. Demonstration of M. esculenta extracts orally result in alteration in (aspartate transaminase (AST), alanine transaminase (ALT) and alkaline phosphatase (ALP) activities, changes in the concentration of urea, cholesterol and other serobichemical parameters, pathological changes in fatal organs, including Necrosis and shrinkage of the glomeruli and aggregates of lymphocytes in the renal cortex was observed, this changes were accompanied with cytoplasmic fatty vacuolation of entrilobula hepatocytes and cerebral neurons. We conclude that Manihot esculenta is toxic causing alteration on various serobiochemical and hematological parameters, this toxicity was correlated to dysfunction of vital organs and we retained all consequence of toxicity to the presence of cyanoginc glycoside; linamarin and lotaustralin.
  
• Evaluation of the Histomorphometric Evidences of Hydroxyurea-induced Testicular Cytotoxicity in Sprague-Dawley Rat
  Hydroxyurea (HDU) is approved for reducing the frequency of painful crises and the need for blood transfusions in adults with sickle cell disease who experience recurrent moderate to severe pain. Treatment with HDU is however, associated with known side effects such as cytotoxicity and myelosuppression. In the present study we evaluated the effect of a clinically relevant dose of HDU used in the treatment in sickle cell disease on the seminiferous tubules of rats. Adult male Sprague -Dawley rats were orally treated with 25 mg HDU kg ^-1 body weight/day for 28 consecutive days. Control rats received the vehicle for HDU which was normal saline 2.5 mL kg ^-1 body weight. Groups of rats were sacrificed variously on the next day, the 56th and the 112 day after the last dosing with HDU or saline. The testis were recovered, weighed and subjected to histopathology. The gross anatomical parameters assessed included the testicular weights and volumes while stereological parameters estimated includes diameter and cross-sectional area of the seminiferous tubules; number of profiles per unit area and numerical density of seminiferous tubules. The results show that treatment with HDU exhibited significant atrophic degeneration in the seminiferous tubules compared with controls. There was an initial manifestation of progressive worsening of the testicular profiles with passage of time, as the animals sacrificed on day 56 demonstrated greater toxicity than those autopsied a day after day 28. However, the animals sacrificed on day 112 showed some improvement in their testicular profiles, suggesting some degree of self-reversal or recovery of the effect. We conclude that HDU has a deleterious effect on the rat testis even at the clinically relevant dose used in management of sickle cell disease.
  
• An Evaluation of Acute and Sub Chronic Toxicological Effects of Hymenocardia acida Leaf Extract in Adult Wistar Rats
  Hymenocardia acida leaf extract is used folklorically as remedy for fever, pain and respiratory diseases. It has also been shown to possess antisickling, antioxidant, antiulcer, anti-arthritic and mutagenic properties, among others. This study was undertaken to ascertain the acute and sub chronic toxicity profile of H. acida ethanol leaf extract administered orally in rats. Acute toxicity test was carried out using modified Lorke's method. Four groups of seven rats each were used for sub chronic toxicity evaluation. The first group served as control, while groups two, three and four received 25, 50 and 100 mg kg ^-1 extract respectively for twenty-nine days. In the acute toxicity test, the extract did not cause any signs of toxicity or produce mortality in rats. Results also showed that sub chronic administration of the extract did not significantly (p>0.05) affect food consumption, body weight and haematological parameters at the doses used. Water intake was observed to increase significantly (p<0.01) in the groups administered 25 and 50 mg kg ^-1 extract during the first and fourth weeks of administration. Relative spleen weights were significantly (p<0.05) lowered in groups given 50 and 100 mg kg ^-1 extract while relative brain weight reduced significantly (p<0.05) in the group administered 100 mg kg ^-1 extract. Serum triglyceride levels were also significantly (p<0.01) elevated in 50 and 100 mg kg ^-1 extract-treated groups, without significant alterations of other biochemical parameters. Microscopically, mild cortical-tubular cellular oedema in kidneys of extract-treated groups was observed. This study shows that although H. acida leaf extract is safe acutely, its long-term use of may be associated with mild renal toxicity.
  
• Ameliorative Activity of Withania somnifera Root Extract on Paraquat-induced Oxidative Stress in Mice
  Paraquat (PQ), an oxidative stress inducing substance, is a herbicide which is very toxic to the animals and humans. A number of antioxidant treatments against PQ-induced oxidative stress have been tried but unfortunately, none of them has been proven to be enormously effective. In this context, attentions are needed to explore the antioxidants from the natural resources. Thus, the antioxidant activity of Withania somnifera (Ws) root extract on paraquat (PQ) induced oxidative stress in mice was investigated. The doses of 100, 250 and 500 mg kg ^-1 of Ws were given orally on alternate day for 30 days. PQ (3.5 mg kg ^-1 ) was injected intraperitoneally on day 15th of start of the study. On day 30th antioxidant activity of Ws was evaluated by measuring lipid peroxides (MDA) and GSH contents as well as by measuring the activities of antioxidant enzymes; superoxide dismutase (SOD) and catalase (CAT) in the blood of mice. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin, creatinine and urea levels were also estimated to investigate the protective effects of Ws on liver and kidney functions. Ws remarkably alleviated the over production of MDA and improved GSH level in PQ intoxicated mice blood dose-dependently. In addition, SOD and CAT activities were improved significantly by Ws treatment. Ws had also considerably alleviated the elevated AST and ALT activities as well as the total bilirubin, creatinine and urea levels in a dose dependent manner. Ws protected the mice against paraquat-induced oxidative stress mainly through alleviating the over production of MDA and modulating the lowered GSH level, SOD and CAT activities. Thus, Ws may constitute an alternative sole or adjunct remedy against paraquat-induced oxidative stress.
  
• Influence of Bosentan on Antidiabetic Effect of Pioglitazone and Nateglinide in Experimental Animals
  The present study was carried out to evaluate the drug-drug interaction between antidiabetic drugs and antihypertensive drug. Interaction of Pioglitazone, the known Thiazolidinedione antidiabetic drug and Nateglinide, the known Meglitinide class antidiabetic drug with Bosentan, an antihypertensive drug was evaluated in healthy and Streptozotocin (STZ) induced diabetic rats. The blood samples were collected from rats at different time interval upto 24 h and blood glucose was estimated. Bosentan (10 mg kg ^-1 , p.o.) pretreatment has not significantly altered the onset of antidiabetic effect of Pioglitazone (0.3 mg kg ^-1 , p.o.) but significantly decreased the peak antidiabetic effect in healthy and Streptozotocin induced diabetic rats (44.74±2.56% reduction before treatment to 34.59±0.25% reduction after treatment), while duration of antidiabetic effect was reduced from 16 h to less than 12 h in both groups. Similarly pretreatment with Bosentan (10 mg kg ^-1 , p.o.) has significantly no effect on the onset of antidiabetic effect of Nateglinide (50 mg kg ^-1 , p.o.) but it significantly reduced the peak antidiabetic effect in healthy and Streptozotocin induced diabetic rats (46.15±1.25% reduction before treatment to 37.57±1.61% reduction after treatment), while duration of antidiabetic effect was reduced from 12 h to less than 8 h in both groups. This study indicates that Therapeutic Drug Monitoring (TDM) has to be required to readjust the therapeutic doses of Bosentan and antidiabetic drugs like Pioglitazone and Nateglinide when they used concomitantly.
  
• Anti-spermatogenic Activity of Leptadenia hastata (Pers.) Decne Leaf Stems Aqueous Extracts in Male Wistar Rats
  Testis histology and sperm parameters were used to evaluate the antispermatogenic effect of Leptadenia hastata aqueous extract in male Wistar rats. 100, 200, 400 and 800 mg kg ^-1 of Leptadenia hastata aqueous extracts were orally administered during 60 consecutive days. L. hastata aqueous extract did not have significant (p>0.05) effect on body, testis and epididymis weights. Testes histology of rats treated with the plant extract showed the decrease of Leydig cells number and the spermatogenesis was been influenced with high doses of L. hastata aqueous extracts. Some sperm parameters as path velocity, progressive velocity, straightness, linearity and motility of spermatozoa were been significantly (p<0.05) decreased. The treated rats with the different amount of L. hastata aqueous extracts showed a significant (p<0.01) reduction in the number of sperm in the testis and the cauda epididymis. Even if its not significant, the extract showed a decrease of testes, epididymis weights and a rarity of Leydig cells. These results confirm the antiandrogenic effect of L. hastata and the claims of breeders that the consumption of the leaves of L. Hastata reduced the fertility of their animals.
  
• Reduction in Platelet Aggregation (in vitro) by Diallyl Sulphide in Female Participants with Type 2 Diabetes Mellitus
  Diallyl sulphide an active principle of garlic has been shown to have many medicinal properties. Thus present study is undertaken to see the effect of diallyl sulphide on platelet aggregation in women participants with type 2 diabetes mellitus. Women participants (18) with type 2 diabetes mellitus with >2 years duration formed the study group. The body mass index of the study group was 26±3.4 kg m ^-2 and age was 47±8.1 years. Platelet aggregation induced by adenosine diphosphate at 10 and 20 μM concentration was measured in platelet rich plasma. The effect of diallyl sulphide (2.2 μg) on platelet aggregation was seen after 1 min of incubation with platelet rich plasma. The women participants were divided into two groups (fast responders for adenosine diphosphate induced aggregation >5.0% slow responders aggregation <5.0%) based on maximal aggregation percentage. The participants had high abdominal circumference (102±9.4) and were hypertensive. Glucose (162.5±47.18) and glycosylated hemoglobin levels (11.7±2.82) suggest lack of metabolic control. The triglycerides levels (185±58.53) were also high. The platelet aggregation with adenosine diphosphate showed variation (10 μM adenosine diphosphate 2.0-81.0% and 20 μM adenosine diphosphate 9.0-93.0%) in fast responders group. The reduction in platelet aggregation with diallyl sulphide also varied with the participants. The relative reduction of adenosine diphosphate induced aggregation with aspirin ranged from 1.0-65.0%. The fibrinogen levels were in normal range. There was reduction in adenosine induced platelet aggregation by diallyl sulphide. The relative reduction in platelet aggregation by diallyl sulphide as compared to aspirin was higher in four participants in fast responder participants. The data unequivocally demonstrated the platelet aggregation inhibition properties of diallyl sulphide.
  
• Anti-inflammatory and In vitro Antioxidant Property of Trigonella foenum graecum Seeds
  Trigonella foenum graecum (Leguminosae) (Eng: fenugreek, Tamil: Vendayam) is a well known spicy agent and seeds are used traditionally for several medicinal purposes. In present study the ethanol extract of seeds from Trigonella foenum graecum (EETFG) was evaluated for its anti- inflammatory activity in acute (carrageenan, histamine and serotonin induced rat paw oedema) and chronic models (cotton pellet induced granuloma). In all models the EETFG (75 and 150 mg kg ^-1 b.wt. p.o.) exhibited significant anti-inflammatory activity (p <0.001) in a dose dependent manner when compared with saline control. Indomethacin (10 mg kg ^-1 b.wt. p.o.) was used as reference drug. The EETFG was evaluated for its antioxidant properties by 1, 1-diphenyl-2-picryl hydrazyl (DPPH) radical scavenging assay and in vitro lipid peroxidation induced by the Fe ²⁺ -ascorbate system in rat liver homogenate. In DPPH radical scavenging assay, the EETFG demonstrated marked and dose dependent free radical scavenging effect and the mean inhibitory concentration (IC ₅₀ ) of the EETFG was found to be 75.2 μg mL ^-1 while the ascorbic acid (reference) exhibited 43.7 μg mL ^-1 . The EETFG effectively inhibited the lipid peroxidation in a dose related manner showing the IC ₅₀ value of 279.1 μg mL ^-1 , whereas the quercetin (reference) showed 46.6 μg mL ^-1 . These findings revealed that the Trigonella foenum graecum seeds had remarkable acute and chronic anti-inflammatory and in vitro antioxidant actions in the tested models validating its traditional uses.
  
• Brain Protective and Erythrocytes Hemolysis Inhibition Potentials from Galls of Guiera senegalensis J.F. Gmel (Combretaceae)
  The purpose of the present study was to investigate the protective effects of the extracts against H ₂ O ₂ -induced hemolysis of erythrocytes and the neuroprotective potential from galls of Guiera senegalensis. Ethyl acetate fraction of aqueous decoction extract (EAF/ADE) significantly (p <0.05) inhibited lipid peroxidation in rat’s brain homogenate in vitro (37.79±0.93% at 1.25 mg mL ^-1 ) when compared to the gallic acid and quercetin used as positive controls and has the best anti-acetylcholinesterase activity (64.02±4.07% at 100 μg mL ^-1 ). Under the oxidative action of H ₂ O ₂ , the extracts from galls of G. senegalensis showed significant protection of the erythrocyte membrane from hemolysis. The Aqueous Decoction Extract (ADE) contains the highest amount of total tannin (25.3±1.55 mg TAE/100 mg of extract) content. The erythrocytes hemolysis inhibitory property from galls of G. senegalensis seems to be related weakly to its total tannin content (p <0.05). The present study thus suggested that the galls from G. senegalensis could be used as a new potential source of natural neuro-protective and antioxidant components.
  
• (-)Epicatechin Regulation of Hydroxysteroid Sulfotransferase STa (rSULT2A1) Expression in Female Rat Steroidogenic Tissues
  The aim of this study was to investigate (-) epicatechin regulation of rSULT2A1 expression in female rat liver, adrenal gland, ovary, and heart. Western blotting and reverse transcription-polymerase chain reaction (RT-PCR) determined protein and mRNA levels, respectively. (-) epicatechin treatment (7 days) significantly inhibited rSULT2A1 protein and mRNA expression in rat ovary and heart but significantly induced that in adrenal gland. No significant changes in rSULT2A1 expression were observed in female rat liver. These results suggest that (-) epicatechin may increase the sulfation of DHEA in the DHEA producing adrenal gland, which will increase the transport and stability of DHEA. While in the target tissues such as heart and ovary, decreased SULT2A1 expression caused by (-) epicatechin will increase the de-sulfation of DHEAS to DHEA to increase the biological activity of DHEA. This may explain the mechanisms for the beneficial effects of (-) epicatechin in heart and ovary. (-) Epicatechin does not affect the detoxification roles of SULT2A1 in liver.
  
• In vitro and in vivo Antioxidant and Toxicity Evaluation of Different Fractions of Oxalis corniculata Linn.
  In course of investigation on natural antioxidants, the present study was aimed to report the antioxidant activities, both in vitro and in vivo , of the crude methanolic extracts of the whole plant of Oxalis corniculata Linn along with its various organic fractions. The different assay methods, including total antioxidant activity, scavenging free radical, authentic peroxynitrite, nitric oxide and reducing power assessment were used to evaluate the antioxidant potential of the crude extract and its organic fractions. The ethylacetate (EtOAc) fraction, showed strong activity in all the model systems tested and in peroxynitrite model this fraction (IC ₅₀ value of 2.29±0.18 μg mL ^-1 ) exerted three-fold stronger activity than standard penicillamine (IC ₅₀ value of 6.20±0.32 μg mL ^-1 ). The reducing power of the extract was found to be concentration dependent. The administration of the extract/fractions at a dose of 250 and 500 mg kg ^-1 body weight to the male Wistar rats increased the percentage inhibition of reduced glutathione, superoxide dismutase and catalase significantly. Whereas, lipid peroxidation level in hepatotoxic rats markedly decreased at a dose of 500 mg kg ^-1 body weight after 7 days. The total phenol and flavonoid content were also measured in the crude extract along with its organic fractions. The Brine shrimp lethality bioassay was used to determine the toxicity of the extracts and Vincristin sulphate was used as positive control. The dichloromethane (CH ₂ Cl ₂ ) fraction showed highest activity (LC ₅₀ value of 29.02±1.16 μg mL ^-1 ) and other showed activity in the order of: EtOAc fraction >n-BuOH fraction> MeOH extract > aqueous fraction. Taken together, these results suggest that O. corniculata extract has strong antioxidant properties and further validate the traditional use of this plant.
  
• Cinnamon Can Replace Harmful Chemicals Used to Create Nanoparticles
  .
  
• Evidence Lacking for Widespread Use of Costly Antipsychotic Drugs, Study Suggests
  .
  
• Inverse Benefits Due to Drug Marketing Undermine Patient Safety and Public Health, Study Finds
  .
  
• Antifertility Activity of Hexane and Ethyl Acetate Extracts of Aerial Parts of Tragia involucrata. Linn
  Many people in rural Bangladesh use a traditional contraceptive pill, “Shanti Bori” to control fertility in which Tragia involucrata is one of the components. The aim of the present study was to evaluate the validity of antifertility effect of this plant. The hexane (HE) and ethyl acetate extracts (EAE) of the aerial parts of T. involucrata have been evaluated for the anti-fertility activity in proven fertile female rats at dose of 200 mg kg ^-1 body weight. Preliminary phytochemical analysis showed the presence of phytosterols, triterpenes and flavonoids in the extracts. HE and EAE showed significant anti-fertility activity. It was found that the extracts reduced the number of litters born significantly at the dose of 200 mg kg ^-1 body weight. HE and EAE exhibited 81 and 50% antiimplantation potency respectively at the tested dose. The extracts also showed the estrogenic activity and potentiated the action of the standard drug ethanyl estradiol. All these observations suggest that extracts have antiimplantation as well as the abortifacient activity and are safe at the effective antifertility doses employed in this study.
  
• 2D Qsar Study of 7-Methyljuglone Derivatives: An Approach to Design Anti Tubercular Agents
  Antitubercular activity of 7-methyljuglone derivatives series were subjected to quantitative structure activity relationship analysis with an attempt to derive and understand a correlation between the biological activity as dependent variable and various descriptors as independent variables. Several statistical regression expressions were obtained using multiple linear regression analysis. The QSAR models were generated using 19 compounds. The predictive ability of the resulting QSAR models was evaluated employing the leave one-out method of cross validation. Several statistical regression expressions were obtained using multiple linear regression analysis. The analysis of best resulted in the following 2-D model which suggests that pIC ₅₀ = [-0.025] MR+[0.278] StrE+[0.028] p+[3.04459] HOMO, n = 19, r = 0.87961, r ² = 0.81048, variance = 0.0805, SD = 0.4324, F = 85.78. The study suggested that substitution of group at R1 and R3 position on naphthoquinones ring with hydrophobic nature and low bulkiness are favorable for the antitubercular activity in the concerned microbes. The quantitative structure activity relationship study provides important structural insights in designing of potent antitubercular agents.
  
• Pattern of Food Poisoning in Egypt, a Retrospective Study
  This retrospective study was conducted at the Poisoning Control Centre, Ain Shams University, Cairo, Egypt with the aim of evaluating the pattern of food poisoning. Hence, the medical profiles of 1748 food poisoning patients, admitted during the period from January 2010 to June 2010, were carefully reviewed. The greatest proportion of food poisoning occurred between the ages of 18 and 29 years, with preponderance of male gender. Most cases of poisoning were accidental. The study revealed that the most common cause involved in acute poisoning was unspecified food poisoning, followed by food contaminated with organophosphate insecticides. Ciguatera and botulism were the third and fourth agents that induced food poisoning. Botulism and organophosphate compounds were the most serious toxicities. All patients had favorable outcome. To achieve a reduction in food poisoning, measures need to be taken across the food chain-from farms to slaughterhouses, food businesses, caterers, consumers and imported foods. Implementation of good hygiene practices and enforcement of legislation are crucial. In addition, strict rules must be followed regarding the sale of insecticides. Establishing poison information centers in different parts of the country, preparing national treatment guidelines, training healthcare providers and ensuring easy availability of the antidotes are also recommended.
  
• Ameliorative Effect of Vitamin E on Chemotherapy Induced Side Effects in Rat Liver
  The aim of the study was to evaluate the extent of change in activities of antioxidant enzymes and lipid peroxidation caused by CPT and protective efficacy of Vitamin E over detrimental effects induced by CPT in male Wistar rat. Male Wistar rats 120±20 g were categorized in four groups. Two groups of rats were administered with CPT (6 mg kg ^-1 intravenously for 4 days); one of these groups received Vitamin E (oral dose of 6 mg kg ^-1 for 30 days) prior to CPT injections. A vehicle treated control group and a Vitamin E control group were also included. CPT treated rats showed significant increase in lipid peroxidation and glycogen levels when compared to control rats. In rats treated with CPT, abnormal changes in activities of enzymic (superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase, glutathione reductase) and non-enzymic (reduced glutathione and Vitamin E) antioxidants were observed. Liver of CPT treated rats showed significant decrease in diagnostic marker enzymes such as aspartate aminotransferase and alanine aminotransferase accompanied with significant increase in alkaline phosphatase and lactate dehydrogenase levels. Pretreatment with Vitamin E reduced the oxidative stress and change in activity of antioxidant enzymes induced by CPT, thereby demonstrating the protection rendered by Vitamin E. Result of the present study suggests that Vitamin E administrated orally protected against oxidation in our experimental models and could be one approach to reducing the risk of CPT-induced side effects in clinical settings.
  
• Antioxidant, Analgesic and Anti-inflammatory Activities of the Herb Eclipta prostrata
  The present study was designed to investigate the antioxidant, analgesic and anti-inflammatory potential of the methanolic extract along with its organic soluble fractions of the herb Eclipta prostrata . In addition, total phenolic and flavonoid content and total antioxidant capacity were also determined. Antioxidant potential of the extract/fractions was evaluated by DPPH (1,1diphenyl-2-picrylhydrazyl), NO (nitric oxide) and ONOO¯ (peroxynitrite) scavenging assay method. Ethyl acetate fractions (EtOAc) showed highest scavenging activity in all the methods with IC ₅₀ value of 12.98±0.08, 45.98±0.07 and 14.45±0.18 μg mL ^-1 for DPPH, NO and ONOO ^- assay method, respectively. In reducing power assay, EtOAc fraction also showed significant (p <0.001) activity. Further, the extract/fractions were studied for their analgesic (hot plate, tail immersion and acetic acid induced writhing test) and anti-inflammatory (carrageenan induced paw edema in rats) activities at a dose level of 200 and 400 mg kg ^-1 body weight. Among all the extract/fractions, EtOAc fraction showed a dose dependent and significant (p <0.005, p <0.05) analgesic activity in all the tested method. EtOAc fractions also reduced the paw edema considerably (86.80% inhibition after 3 h, p <0.005, p <0.05) in dose dependent manner compared to carrageenan induced rat. Altogether, these results suggest that the MeOH extract and its organic soluble fractions could be used as a potential antioxidant, analgesic and anti-inflammatory agent.
  
• Hypoglycemic, Antidiabetic and Toxicological Evaluation of Momordica dioica Fruit Extracts in Alloxan Induced Diabetic Rats
  The aim of the study was to evaluate the antidiabetic effect of Momordica dioica fruit extracts in alloxan induced diabetic wistar rats. Aqueous extract of Momordica dioica (AEMD) showed maximum fall (52.8%) in 0 to 1 h Fasting Blood Glucose (FBG) in Glucose Tolerance Test (GTT) compared to hexane (39%), chloroform (37.2%) and ethanol (37.7%) extract in normal healthy rats. Since AEMD exhibited maximum hypoglycaemic activity as compared to other extracts, it was further studied for antidiabetic effect in diabetic rats. The oral Effective Dose (ED) of AMED was 200 mg kg ^-1 body weight which produced a fall of 57.5% (p<0.001) in diabetic rats. The 200 mg kg ^-1 body weight AMED once daily for 21 days reduced the elevated Blood Glucose (BG) by 64.8% (p<0.001), Post Prandial Glucose (PPG) by 76.9% (p<0.001) and glycosylated hemoglobin (HbA1c) by 37.6% (p<0.001). Urea, creatinine and urinary sugar, total protein, AST, ALT, alkaline phosphatase and bilirubin activities were also reduced after AEMD treatment in diabetic rats. Above 3 g kg ^-1 b.wt was Lethal dose of AEMD i.e., 15 times of ED indicating high margin of safety. Our study suggests possible use of aqueous extract of fruits of M. dioica for the management of diabetes mellitus.
  
• Antioxidant, Anti-inflammatory and Anti-pyretic Activities of Trichosanthes dioica Roxb. Fruits
  The present study was designed to investigate the antioxidant, anti-inflammatory and antipyretic potential of the methanolic extract along with its organic soluble fractions of the fruits of Trichosanthes dioica Roxb. Antioxidant potential of the extract/fractions was evaluated by DPPH (1,1diphenyl-2-picrylhydrazyl) and NO (nitric oxide) scavenging assay method. Ethyl acetate fractions (EtOAc) showed highest scavenging activity in all the methods with IC ₅₀ value of 12.32±0.16 and 5.38±0.07 μg mL ^-1 for DPPH and NO assay method, respectively. In reducing power assay, EtOAc fraction also showed significant (p <0.001) activity. Further, the extract/fractions were studied for their anti-inflammatory (carrageenan induced paw edema in rats) and antipyretic (Brewer’s yeast induced pyrexia) activities at a dose level of 100, 200 and 400 mg kg ^-1 body weight for MeOH extract. Methanolic extract showed a dose dependent and significant (p <0.005, p <0.05) anti-inflammatory and antipyretic effect. Dichloromethane fraction (CH ₂ Cl ₂ ) and Ethyl acetate fractions exhibited similar activity using a dose of 200 mg kg ^-1 b.wt. in these models. The pharmacological activities of the (CH ₂ Cl ₂ ) fraction were lesser than the MeOH extract and other fractions. In addition, total phenolic and flavonoid content and total antioxidant capacity were also determined. Altogether, these results suggest that the MeOH extract and its organic soluble fractions EtOAc could be used as a potential antioxidant, anti-inflammatory and antipyretic agent.
  
• Efficacy and Safety of Diclofenac Sodium and Aceclofenac in Controlling Post Extraction Dental Pain: A Randomised Open Label Comparative Study
  The aim of this study was to evaluate the efficacy and safety of newer drug Aceclofenac 100 mg BD compared to Diclofenac Sodium 50 mg three times daily tid in post extraction dental pain. A total number of 100 patients posted for third molar extraction were recruited for the study. Those who met the inclusion criteria (n = 51) were randomized into two treatment groups A and B. Group A received T. Diclofenac Sodium and Group B received T. Aceclofenac. On the day of surgery patients were given the study drugs and Visual Analog Scales (VAS) to assess the pain intensity for 5 days. Baseline pain intensity immediately after surgery and at 8 h was recorded on the day of surgery. On day 5 evaluated statistically using one way analysis of variance. The statistical analysis of pain intensity using VAS showed that 78% of patients showed severe baseline pain intensity and at the end of 8 h on the first day of surgery, Diclofenac group showed 27% reduction in pain intensity and 40% reduction in Aceclofenac group (p<0.05). On day 5 pain reduction was 95% and 100% in Diclofenac and Aceclofenac group, respectively. Global assessment and safety assessment showed better gastrointestinal profile for the Aceclofenac than Diclofenac sodium. It proves that Aceclofenac has a rapid onset and prolonged pain relief and statistically significant analgesic effect in the immediate postoperative period of 8 h in comparison to Diclofenac sodium.
  
• Inhibitory Effect of Metabolites from Probiotics Lactobacillus acidophilus Strains on Growth of Pathogenic Bacteria
  In the present study, the effects of combined metabolites produced by lactic acid bacteria were tested on food pathogenic and contaminant microorganisms. Totally, eight strains of Lactobacillus acidophilus (FTDC 2804, FTDC 0785, FTDC 8592, FTDC 1295, FTDC 4793, FTDC 4462, FTDC 0582 and FTDC 2916) were used which cultivated in four types of agro waste substrates including pineapple waste, soy whey, cabbage and molasses. The inhibitory effects of L. acidophilus metabolites (lactic acid, hydrogen peroxide, acetaldehyde, diacetyl and bacteriocin) were determined by agar well diffusion method on two pathogenic bacteria; Staphylococcus aureus and Escherichia coli . Metabolites of different L. acidophilus strains cultured in different agro waste substrates showed diverse inhibitory effects. Among all, the highest inhibition zone was obtained with the strains cultivated in pineapple waste, such as, L. acidophilus FTDC 4462 strain (10.57±0.10 mm for S. aureus and 11.13±0.45 mm for E. coli ). It can be concluded that L. acidophilus species has the ability to grow in agro waste materials and produce beneficial metabolites with antibacterial activities.
  
• Anti-Nociceptive, Anti-Inflammatory and Anti-Oxidant Effects of the Methanol Leaf Extract of Sterculia tragacantha Lindl
  The anti-nociceptive, anti-inflammatory and anti-oxidant activities of Sterculia tragacantha were evaluated in this study. The extract was also subjected to acute toxicity and phytochemical tests. It was demonstrated that pretreatment of mice with the extract significantly inhibited acetic acid induced pain and carrageenan-induced paw edema. Daily dosing of 300 and 600 mg kg ^-1 of the extract significantly suppressed granuloma formation in mice. The extract showed significant anti-oxidant activity. Phytochemical screening showed that the extract contained alkaloids, flavonoids, tannins, glycosides and saponins. It was concluded that Sterculia tragacantha used in the present study, possesses anti- inflammatory, anti-nociceptive and anti-oxidant activities.
  
• Diuretic Activity of Leaves Extract of Hot Water Infusion of Ruta graveolens L. in Rats
  Ruta graveolens Linn (Family: Rutaceae) leaves are used in Sri Lankan traditional medicine as a diuretic but this effect is not scientifically validated. This study has evaluated the diuretic potential of R. graveolens leaves in rats using a Hot Water Infusion (HWI). Different concentrations of HWI (4.5, 6.75, 9.0 mg mL ^-1 ) or vehicle or furosemide (13 mg kg ^-1 ) were orally administrated (n = 6 per group) to hydrated rats and their urine output was monitored hourly for 6 h. Urinary pH, specific conductivity, specific gravity, Na ⁺ , K ⁺ , Cl¯ levels and creatinine clearance were determined (with the highest dose and control). Using these data standard urinary indices were calculated. Further, subchronic toxicity was examined in terms of serum Glutamic Oxaloacetic Transaminase (GOT), Glutamic Pyruvic Transaminase (GPT), urea and creatinine levels and overt signs. HWI increased the urine output markedly in a dose-dependent manner. The high dose of HWI was almost equipotent to furosemide (in terms of diuretic activity). The onset of diuresis was very rapid (within 1 h) and lasted throughout the studied period. HWI also caused significant increase in specific gravity, specific conductivity, creatinine clearance, Na ⁺ and K ⁺ levels, thiazide secretion index, urine alkaline index, diuretic action, Na ⁺ and K ⁺ saliuretic indices and significant decrease in carbonic anhydrase index. Further, no evidence of subchronic toxicity was seen. R.graveleons leaves exhibits safe and strong oral diuretic activity as claimed in Sri Lanka traditional medicine. This action is mediated via multiple mechanisms: thiazide like activity, inhibition of carbonic anhydrase activity and increase in glomerular filtration rate.
  
• Evaluation of Anti-asthmatic Activities of Ixora coccinea Linn (Rubiaceae)
  Ixora coccinea L. (Rubiaceae) possess anti-inflammatory and antitussive properties. It is traditionally used for various respiratory ailments including catarrhal bronchitis cough and asthma. In the present study we investigated anti-asthmatic properties of an hydroalcoholic leaf extract of I. coccinea in an ovalbumin (OVA)-induced asthmatic rat model. We also evaluated the anti-allergic property of the extract by Abdominal Wall (AW) method and histamine-induced cutaneous reaction. Rats were sensitized with intraperitoneal (i.p.) ovalbumin and challenged by OVA intranasally to induce chronic airway inflammation. Randomized treatment groups of sensitized rats received I. coccinea extract or distilled water. I. coccinea extract at doses of 1000 and 1500 mg kg ^-1 suppressed eosinophilia and significantly inhibited AHR in rat with OVA-induced asthma. Based on lung histopathological study using hematoxylin and eosin I. coccinea reduced inflammatory cell infiltration and repaired epithelial cells damaged. In addition the extract at the same doses significantly decreased the diameter of the blue spot (16 and 55%, respectively) compared with the controls and inhibited the skin reactions induced by histamine (23.55 and 53.36%, respectively). In conclusion our results provide evidence that I. coccinea has anti-asthmatic properties and then can support its use in folk medicine to treat asthma.
  
• Study of Urinary Biomarkers for Nephrotoxicity in Wistar Rats
  Nephrotoxicity is the second most persistent cause of drug withdrawal. In this study, we have determined the presence of nephrotoxic biomarkers in experimentally-induced site specific kidney injury. This study include measurement urinary clusterin, microalbumin, traditional serum nephrotoxic biomarkers (creatinine, urea, albumin, total protein), qualititative urine analysis and histopathological examination of kidney in rat models treated with carboplatin and ibuprofen-induced renal tubular injury. Female wistar rats were divided into four groups of six animals each were treated as follows: (1) Normal saline (0 mg kg ^-1 intraperitoneally) (2) Carboplatin (250 mg kg ^-1 , intraperitoneally) (3) 0.5% Carboxy methyl cellulose (0 mg kg ^-1 , orally) (4) Ibuprofen (800 mg kg ^-1 , orally). Blood urea levels increased significantly in response to carboplatin and ibuprofen treated rats indicating potential nephrotoxicity. In carboplatin and ibuprofen treated rats, urinary clusterin was dramatically increased indicating dysfunction of proximal tubule. Additionally carboplatin and ibuprofen treated rats showed proteinuria, microalbuminuria and hypoalbuminemia revealing dysfunction of either distal tubule or loop of henle. The data suggested potential proximal tubular damage alongwith damage to distal tubule and loop of henle in presence of carboplatin and ibuprofen. Therefore, combinatorial measurement of clusterin and microalbumin with other nephrotoxic biomarkers such as kidney injury molecule-1, Cystatin C, Beta-2 microalbumin and trefoil factor 3 might work as powerful tool for highly effective screening of nephrotoxicity.
  
• Effects of Aqueous Extract of Khaya senegalensis Stem Bark on Biochemical and Hematological Parameters in Rats
  In this study, the effects of aqueous extract of Khaya senegalensis stem bark on hematological and biochemical parameters were investigated in rats. The rats were randomly divided into four groups of 5 rats per group. Group I (control) received normal saline while Groups II, III and IV were fed 50, 100 and 200 mg kg ^-1 of Khaya senegalensis stem bark extract orally for 21 days. Repeated administration of the extract resulted in a dose-dependent increase in total protein, globulin, urea and creatinine. The extract also produced an increase in the plasma levels of some liver enzymes namely Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) and Alkaline Phosphatase (ALP). These changes were significant (p <0.05) with 100 and 200 mg kg ^-1 of the extract. At this same dose range, the extract caused a significant decrease in Red Blood Cells (RBC), Packed Cell Volume (PCV) and Hemoglobin level (Hb). In contrast, serum sodium ion (Na ⁺ ) and potassium (K ⁺ ) ion concentrations were elevated following the administration of the extract but there were no significant changes in the serum chloride (Cl¯) and bicarbonate ions (HCO ₃ ¯) concentrations. The results of this study suggest that prolonged use of aqueous extract of Khaya senegalensis stem bark extract may adversely affect vital organs in the body.
  
• Evaluation of Antinociceptive and Antidiarrhoeal Properties of Pistia stratiotes (Araceae) Leaves
  Pistia stratiotes (Araceae) is a Bangladeshi medicinal plant used traditionally to treat a various diseases. The present study was designed to investigate of antinociceptive and antidiarrhoeal activity of methanolic extract of the leaves of Pistia stratiotes . The extract produced significant writhing inhibition in acetic acid-induced writhing in mice at the oral dose of 250 and 500 mg kg ^-1 body weight (p<0.001) comparable to the standard drug diclofenac sodium at the dose of 25 mg kg ^-1 of body weight. The extract showed antidiarrhoeal activity on castor oil induced diarrhoea in mice, it increased mean latent period and decreased the frequency of defecation significantly at the oral dose of 250 and 500 mg kg ^-1 body weight (p<0.01) comparable to the standard drug Loperamide at the dose of 50 mg kg ^-1 of body weight. The obtained results provide a support for the use of this plant in traditional medicine and its further investigation.
  
• Phytopharmacological Evaluation of Ethanolic Extract of the Seeds of Abrus precatorius Linn
  Abrus precatorius Linn. is a leguminous plant of the fabaceae family whose stem, bark, leave and roots are widely used for medicinal purposes in tropical and subtropical regions of the world. The plant parts are purgative, emetic, tonic, anti-phlogistic, aphrodisiac and anti-ophthalmic agents. The purpose of the present investigation was to study antioxidant, anti-inflammatory and analgesic activity of Abrus precatorius Linn. ethanolic seed extracts by soxhlet method. The free radical scavenging activity of extract was carried out by 1,1-diphenyl-2-picrylhydrazyl method and anti-inflammatory activity by carrageenan induced rat paw edema and analgesic activity carried out by tail flick and tail immersion method. The extract showed significant activity i.e., 80.1±0.34% at 300 μg mL ^-1 . The extract was evaluated for its anti-inflammatory activity it showed significant anti-inflammatory activity i.e., 62.68% at 375 mg kg ^-1 by carrageen induced method. Further, the extract was evaluated for analgesic activity and the extract showed significant activity at 300 mg kg ^-1 after 90 min interval by tail flick and tail immersion method. As ethanolic extract of Abrus precatorius Linn. was found to have potent antioxidant, anti-inflammatory and analgesic potential. The present study concludes that seeds of Abrus precatorius Linn. can be used as good natural antioxidant to treat free radical induced disease.
  
• Hypolipidemic Properties of Rhinacanthus nasutus in Streptozotocin Induced Diabetic Rats
  Diabetes mellitus is one of the widespread and severe metabolic disorders in humans all over the globe. Various medicinal plants have effectively been used to conquer this global health problem. Rhinacanthus nasutus is widely used in Thai medicine and various parts of the world to treat different diseases i.e., cancers, skin diseases, ringworm etc. The methanolic extract of R. nasutus was administered to streptozotocin induced (50 mg kg ^-1 b.wt.) diabetic male albino wistar rats for 30 days to identify its effect on serum and hepatic cholesterol levels. Oral administration of R.nasutus (200 mg kg ^-1 b.wt.) significantly decreased the serum total cholesterol, triglycerides, LDL-cholesterol and increased the HDL-cholesterol levels. The hepatic total cholesterol, triglycerides, phospholipids were also decreased after administration of R. nasutus in diabetic rats. The results of this experimental study indicate that R. nasutus possesses hypolipidemic activity without evident toxic effects to the experimental animal.
  

  No Issue Number

• Antifungal Potency of Turtle Eggshell Extract
  Indonesia as tropical country is endemic to various infectious diseases, including that affecting the skin due to fungi infection. In nature, the eggshell, present as hard or soft shell, protects the embryo from microorganism infection. Turtle produces soft shells, which is very unique in that it does not contain albumin. In nature, the turtle eggshell has to cope with high humidity, so it is assumed that turtle soft shell has potent antifungal activity. This study investigated the potency of the eggshell extract from green sea turtle ( Chelonia mydas ) as an antifungal against Candida albicans , Trichophyton mentagrophytes , Microsporum gypseum and Aspergillus brasiliensis . Protein extraction was carried out with dialysis followed by lyophilization and sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Antifungal activity assay was conducted by Dilution Plating method with nystatin as a standard drug. The possible mechanism of antifungal activity was assessed using Scanning Electron Microscopy (SEM). Fungal growth was inhibited by 8% w/v or 8x10 ⁴ ppm extract, equivalent to 0.53 ppm nystatin against Candida albicans , 0.55 ppm against Microsporum gypseum , 0.36 ppm against Trichophyton mentagrophytes and 0.35 ppm against Aspergillus brasiliensis . The SDS-PAGE showed that the turtle eggshell extract had 6 proteins with molecular weight 20; 45, 50, 66, 80 and 116 kDa. This study showed that 8% w/v green turtle eggshell extract has inhibitory activity against Candida albicans , Trichophyton mentagrophytes , Microsporum gypseum and Aspergillus brasiliensis , as also proven by SEM results. Taken together, the present results showed that turtle eggshell extract has antifungal potency that could be developed as antifungal drug.
  
• Cell Stress, Hypoxic Response and Apoptosis in Murine Adriamycin-induced Nephropathy
  Adriamycin (ADR)-induced nephropathy in rodents is an experimental model commonly used for studies of chronic human renal diseases. The molecular associations involved in renal apoptosis linked to hypoxia and cell stress response in this model are not completely known. The aim of this study was to determine the associations among the expression patterns of the Inducible Nitric Oxide Synthase (iNOS), the heat shock protein 60 (Hsp60) and the Hypoxia Inducible Factor-1 Alpha (HIF-1α) linked to apoptosis in renal cortex in the nephrotic syndrome progression induced by ADR administration. Male BALB/c mice were treated with a single dose of ADR (11 mg kg ^-1 ; i.v.). Tubulointerstitial nephrosis was monitored by histopathological assessment and by biochemical determinations on 7, 15 and 30 days following drug exposure. These results were evaluated in conjunction with renal expression of iNOS, Hsp60 and HIF-1α. Cortical apoptosis was examined by TUNEL assay. The increment of renal apoptotic cells in tubulointerstitial areas was accompanied by the decrease in Bcl-x _L /Bax ratio and the enhancement of the active caspase-3 and Hsp60 expressions from day 7 onwards. iNOS and HIF-1α increased concomitant with the renal apoptosis and the tubule interstitial injury. Taking the previous information into account, data indicate that the over expression of renal HIF-1α, iNOS and Hsp60 are concurrent with the apoptotic events triggered by ADR. These results contribute to additional knowledge of the molecular complex events involved in the context of ADR-induced nephropathy progression.
  
• Acute and Sub Chronic Oral Toxicity Assessment of the Ethanolic Extract from the Rind of Nephelium lappaceum in Rats
  Nephelium lappaceum is a tropical fruit native to Malaysia. The rind of N. lappaceum , is having extremely high antioxidant and free radical scavenging activities. The ethanol extract from the rind of Nephelium lappaceum was evaluated for acute and sub-chronic toxicity study in Sprague Dawley rats. In the acute study, a single oral administration of N. lappaceum rind extract (50, 200, 1000 and 2000 mg kg ^-1 ) was administered to rats for 14 days. In the sub chronic toxicity study, the extract was administered to rats (500, 2000 mg kg ^-1 ) for 28 days. There was no mortality, or adverse effects observed in rats. There was no significant difference observed in relative organ weights and the biochemical analysis (serum urea, creatinine, ALP, AST and total protein). Histological observation of liver and kidney also did not reveal any significant changes. In conclusion, present study showed that the lethal dose of ethanol extract of Nephelium lappaceum rind is more than 2000 mg kg ^-1 and there is a huge margin of safety for the therapeutic use. No-observed-adverse-effect-level (NOEL) of the extract is considered to be up to 2000 mg kg ^-1 day ^-1 for 28 days in rats.
  
• Antihypertensive Potency of Wild Cosmos (Cosmos caudatus Kunth, Asteraceae) Leaf Extract
  The wild cosmos ( Cosmos caudatus Kunth, Asteraceae) is one of the vegetables mostly consumed by rural people of Central and East Java Provinces of Indonesia and those of the Malay Peninsula. Yet, it has not been widely used medicinally. The leaf has distinctive taste as well as odor and contains high level of flavonoid, especially flavonol and flavon glycosides which have potent antioxidant activity. In this study, in an attempt to explore the antihypertensive effect, wild cosmos leaf aqueous extract was tested in rats treated with adrenaline and sodium chloride. The frequency of heart rate and amplitude of stroke volume were measured using the non-invasive tail cuff method. The extract at doses of 500 and 1000 mg kg ^-1 showed similar potency to that of 9 mg kg ^-1 atenonol, in lowering both parameters, induced by adrenaline. However, after sodium chloride, the extract only suppressed the amplitude and this effect was comparable to that of 0.45 mg kg ^-1 hydrochlorothiazide and 13.5 mg kg ^-1 captopril. Besides cardiac effects, the extract also demonstrated diuretic activity which was comparable to that of 1.8 mg kg ^-1 furosemide. Taken together, results of present study suggest that wild cosmos leaf extract have antihypertensive effect which may be related, at least in part, to the decreased cardiac output and induction of diuresis. The results may further indicate that consumption of wild cosmos leaf in diet is beneficial for hypertensive patients.