Nayara S. Raulino Silva, César F. Santos, Luana K. S. Gonçalves, Francinaldo S. Braga, Jonathan R. Almeida, Clarissa S. Lima, Davi S. B. Brasil, Carlos H. T. P. Silva, Lorane I. S. Hage-Melim, Cleydson Breno R. Santos
Aims: To study the Structure-Activity Relationship (SAR) and pharmacokinetic and toxicological properties (ADME/Tox) of the major compounds of sesquiterpenes class oil-resin extracted from the copaiba, using quantum chemistry methods B3LYP/6-31G*, employing the resulting information as a guide to obtain more stable compounds, less reactive and toxic with better absorption, distribution, metabolism and excretion. Place and Duration of Study: Laboratory of Modeling and Computational Chemistry (LMCC) at Federal University of Amapá (UNIFAP), Macapá, Brazil, between March 2014 and February 2015. Methodology: Major compounds were selected from the literature, totaling 12 compounds, and modeled with the GaussView 5.0 program. The optimization was performed using the DFT method and B3LYP/6-31G* base set implemented in the Gaussian 03 program. Maps of molecular electrostatic potential (MEP's) were generated from the atomic charges, and the construction of the MEP's and frontier orbital’s (HOMO and LUMO) were visualized with the aid of Molekel program. Pharmacophore pattern was determined from the online server PharmaGist, and the ADME/Tox properties of the compounds studied were calculated using the online server PreADMET and the results were compared with those of DEREK software. Results: MEP's in the compounds studied have shown no uniformity in their region of electrostatic potential. HOMO is localized to at the double bonds (C=C), and LUMO orbitals were on the carbon atoms of the double bonds. Pharmacophore pattern evidenced 11 regions hydrophobic. Pharmacokinetic property of human intestinal absorption (HIA) was 100% for all compounds. Cell permeability PCaCO2 was classified as medium, and the values ranged from 56.3475 nm/sec (compound 2) to 23.405 nm/sec (compound 10). Cell permeability PMDCK was classified as high, because presented higher values than 25 nm/sec, ranging from 218.885 nm/sec (compound 2) to 40.0711 nm/sec (compounds 7 and 11). The compounds showed strong plasma protein binding with values ranging from 90.849656% (compound 2) to 100% for the other compounds. Penetration of the blood brain barrier was classified as active (CBrain/CBlood>1), and the values ranged from 3.75249 (compound 2) to 15.0642 (compound 10). Therefore, these compounds studied evidenced toxic effects on the CNS. In toxicity tests, the compounds 1-2, 4-6 and 8-10 show mutagenic predictions, and only the compounds 3, 7, 11 and 12 presented non-mutagenic predictions. Carcinogenicity was significant in mouse. However, the predictions in rats the compounds 1-4 and 6-12 presented positive predictions (non-carcinogenic), and only the compound 5 showed a negative prediction (evidence of carcinogenicity), when analyzed in DEREK software the compounds showed no toxiphoric alerts generated by epoxides groups. Conclusion: The B3LYP/6-31G* method was adequate to optimize the major compounds of copaiba oil-resin. Compounds studied are viable for administration in different pathways, and may have their improved pharmacokinetic properties according to the formulation to enhance the efficacy and safety.
Aims: Antivenom has been used successfully for more than a century as the only effective treatment for scorpion stings. Orthochirus iranus scorpion venom has high toxicity and preparation of antivenom is necessary for the treatment of its toxic effects. In this study, we prepared Orthochirus iranus scorpion venom-loaded nanoparticles as a vehicle to deliver of antigen for the purpose of use for antivenom preparation. Study Design: Advanced nanotechnology based antigen delivery system study. Place and Duration of Study: Department of Human Vaccines and Sera, Razi Institute, Karaj, Iran, between May 2011 and August 2014. Methodology: Nanoparticles were prepared by an ionic gelation method. Factors affecting the loading capacity, efficiency, morphology, surface properties, zeta potential, particle size, particle size distribution, and structure of nanoparticles and venom were investigated and optimized. Results: In optimal conditions, particle size, zeta potential, and particle size distribution of venom-loaded nanoparticles were 83 nm, 36.7 mV, and 0.256, respectively. The nanoparticles showed a smooth surface and spherical shape. The optimal initial concentration of venom was 500 µg/ml with a loading capacity of 80.48% and efficiency of 98.99%. FTIR spectra of nanoparticles and venom-loaded nanoparticles indicated chemical and physical bonds between chitosan, TPP and venom, and evidence of entrapment of venom in the nanoparticle matrix. Conclusion: We concluded that Orthochirus iranus scorpion venom-loaded chitosan nanoparticles could be used for antigen delivery.
Aim: Diabetes is the most common and one of the leading causes of mortality among non communicable diseases. Pilogitazone is the potent PPARr agonist used for the treatment of diabetes. The drug is associated with a substantial weight gain. The aim of this present study is to try to reduce the drug associated weight gain by co-administration with Piperine. Methods: Alloxan induced diabetic model was taken as experimental method. After induction of diabetes (except in Group I), animals were classified into five groups, Group I and II were not given with any treatment and they served as normal control and diabetic control groups respectively. Group III, IV and V were given with Pioglitazone (2 mg/Kg PO), Piperine (2 mg/Kg PO) and co-administration of both at 2 mg/Kg PO respectively for 4 weeks. After completion of 4 weeks, the blood samples of the animals were estimated for the glucose levels to analyze the diabetic action and the lipid profile along with observation of body weight, food intake and water intake to analyze weight gain. Results: There was a good control over the blood sugar levels in all the treated groups (≈ 120 mg/dL) except in diabetic control group (330.0±9.661 mg/dL). Along with a control over diabetes, Piperine and Pioglitazone treated animals resulted in reduced lipid profiles and not much increase in weight gain (1.243±0.137%) when compared to monotherapy of Pioglitazone (8.818±0.846%). Conclusion: Co administration of Piperine in diabetic treatment with Pioglitazone may be a beneficial attempt to reduce weight gain.
Aim: The objective of this study was to determine the preventive role of Tanopati against doxorubicin induced myocardial toxicity in rats. Study Design: Randomized experimental controlled study. Place and Duration of Study: This study was carried out in Laboratory of Biochemical Pharmacodynamy, Félix Houphouët-Boigny University of Abidjan, Côte d’Ivoire between July 2014 and January 2015. Methodology: Twenty five albino Wistar rats, divided into five groups with five rats each, were used in this study. Cardiotoxicity was induced by doxorubicin(dox) (15 mg/kg for 2 weeks). Tanopati (10 mg/kg orally) or vitamin E (100 mg/kg orally) was administered as pretreatment for two weeks, and followed by dox for another two weeks. Biomarkers like lactate dehydrogenase (LDH), creatine phosphokinase (CK), iso enzyme CKMB, lipid peroxidation activity, antioxidants such as glutathione (GSH), and antioxidants enzymes such as glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) levels were monitored 36 hours after administration of the final dose. Histopathological examination was performed. Results: The repeated administration of dox (2.5 mg/kg of body weight) caused cardiomyopathy associated with an antioxidant deficit. Pretreatment with Tanopati decreased LDH (417.6±1.17 to 324.6±1.7 UI/L), CK (328.2±0.8 to 230.5±1.09 UI/L) and CKMB (234.9±1.03 to 172.2±2.06 UI/L) levels compared to the values in the control group. Tanopati significantly protected the myocardium from the toxic effect of dox, by increasing the levels of antioxidants such as GSH (1.56±0.03 to 1.76±0.02 nmol /g of heart tissue), SOD (21.66±0.34 to 29.93±0.13 U/g of protein), and CAT (40.13±0.65 to 46.57±0.55 µmol H2O2/min/mg of protein) and decreasing the level of malondialdehyde (MDA) (48.09±1.0.83 to 25.46±0.7 nmol/g). Tanopati also reduced the severity of cellular damage of the myocardium as observed microscopically. Conclusion: The results obtained suggest that cardioprotective effect of Tanopati might be attributed to its antioxidant activity.
Introduction:Azadirachta indica and Maclura tinctoria are two plants that have been reported with some ability to inhibit the growth of different types of bacteria so the aim of this project was to evaluate the in vitro antibacterial activity of the extract of Maclura tinctoria and Azadirachta indica on Streptococcus mutans and Porphyromonas gingivalis. Methods: Ethanol extracts were obtained from Azadirachta indica and Maclura tinctoria. Antibacterial activity was evaluated on S. mutans (ATCC25175) and P. gingivalis (ATCC33277) determining the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) using broth dilution tests. An analysis of variance (ANOVA) was performed followed by Dunnett's post-test for multiple comparisons, considering the value P < 0.05. Results:Azadirachta indica showed a MIC of 500 Ppm (µg/mL) for both bacteria, showing bacteriostatic activity. M. tinctoria at a concentration of 125 Ppm (µg/mL had a bacteriostatic activity and bactericidal at higher concentrations of 250 Ppm (µg/mL and 500 Ppm (µg/mL for S. mutans. Against P. gingivalis the extract presented a MIC and a MCB of 500 Ppm µg/mL).
Discussion:Azadirahcta’s indica and Maclura’s tinctoria ethanol extracts showed inhibitory activity against S. mutans (ATCC25175) and P. gingivalis (ATCC33277) of considerable value. Therefore it is recommended to continue with further studies.
A simple RP-HPLC method with more accuracy and precission was developed for determination of Rifampicin and Isoniazid simultaneously. A mobile phase consisted of methanol, acetonitrile and water in the ratio 60:20:20(v/v) was used, at a flow rate of 1 mL/min. The wavelength of detection was 254 nm and the column used was Kromasil C18, (250 x 4.6 nm, 5 µm). The retention time for rifampicin and isoniazid are 3.42 and 7.43 min respectively. A concentration range of 40-100 µg/mL was studied to test the linearity of the developed method. The correlation coefficient (r2) of regression was found to be 0.998 which is almost equal to 1. The LOQ was 1.75 µg/mL for both rifampicin and isoniazid and the LOD was 0.5 µg/mL for both rifampicin and isoniazid. The mean percentage recovery of rifampicin was 99.56% and 99.83% for isoniazid respectively.
Antibiotics are one of the most important weapons in fighting bacterial infections and have greatly benefited the health-related quality of human life since their introduction. Infectious diseases caused by microorganism are still a major threat to health, despite the tremendous progress in human medicine. Dramatic increase in microbial resistance to antimicrobial agents is well known. Such situation leads the necessity for development of new anti-microbial agents in order to treat the infectious disease in an effective manner. The Medicinal plants are considerably useful and are rich in a wide variety of secondary metabolites such as tannins, alkaloids and flavonoids, which have been found in vitro to have antimicrobial properties. Several attempts are continued to identify the potential antimicrobial agent from the natural resources.
Considering the enormous potentiality of plants as sources for antimicrobial drugs with reference to antibacterial agents, a systematic review was undertaken in the present article for antimicrobial potential of Cassia genus.