Mir Muhammad Nasir Uddin

Effects of Antipsychotics on the Inflammatory Response System of Patients with Schizophrenia in Peripheral Blood Mononuclear Cell Cultures

Objective We investigated the effects of antipsychotics on immune-challenged peripheral blood mononuclear cell (PBMC) cultures. Methods Blood samples were collected from twelve patients with first-episode schizophrenia. The PBMCs were separated and cultures were prepared and stimulated with lipopolysaccharide (LPS) or polyinosinic:polycytidylic acid (poly[I:C]), and then separately treated with a typical antipsychotic (haloperidol) or atypical antipsychotic (clozapine, quetiapine, or risperidone). Pro-inflammatory (interferon gamma [IFN-γ]) and anti-inflammatory (interleukin [IL]-4 and IL-10) cytokine levels were measured in the LPS- or poly(I:C)-stimulated PBMC cultures treated with antipsychotics. Results Haloperidol and quetiapine significantly increased the IL-4 levels (p<0.05) in LPS-stimulated PBMC cultures, while clozapine and quetiapine significantly enhanced the IL-4 levels (p<0.05) in poly(I:C)-stimulated PBMC cultures. Only treatment with haloperidol resulted in a significant increase in IL-10 production (p<0.05) in LPS-stimulated PBMC cultures, whereas clozapine, quetiapine, and risperidone treatment significantly increased IL-10 production (p<0.05) in poly(I:C)-stimulated PBMC cultures. All of the antipsychotics reduced the IFN-γ level significantly (p<0.05) in LPS- and poly(I:C)-stimulated PBMC cultures. Conclusion Antipsychotic treatment altered immune function by raising the levels of anti-inflammatory cytokines (IL-4 and IL-10) and suppressing the levels of pro-inflammatory cytokines (IFN-γ).

Molecular docking of fisetin with AD associated AChE, ABAD and BACE1 proteins.

Alzheimer׳s disease (AD) is one of the most common dementias showing slow progressive cognitive decline. Progression of intracerebral accumulation of beta amyloid (Aβ) peptides by the action of amyloid binding alcohol dehydrogenase (ABAD), a mitochondrial enzyme and β-site amyloid precursor protein cleaving enzyme 1 (BACE1) and the degradation of Acetylcholinesterase (AChE) the main pathological characteristics of AD. Therefore, it is of interest to evaluate the importance of fisetin (a flavonol that belongs to the flavonoid group of polyphenols) binding with AChE, ABAD and BACE1 proteins. Docking experiment of fisetin with these proteins using two different tools namely iGEMDOCK and FlexX show significant binding with acceptable binding values. Thus, the potential inhibitory role of fisetin with AD associated proteins is documented.

Effect of GSTP1 and ABCC4 gene polymorphisms on response and toxicity of cyclophosphamide-epirubicin-5-fluorouracil-based chemotherapy in Bangladeshi breast cancer patients.

The most important cytotoxic drug namely, cyclophosphamide used in breast cancer along with epirubicin and 5-fluorouracil, is transported by ABCC transporters and detoxified by glutathione S-transferases (GSTs). The activities of these enzymes and transporters may vary in different population due to the presence of genetic polymorphisms. This study was aimed to evaluate the effects of GSTP1rs1695 and ABCC4rs9561778 polymorphisms on the response and toxicities produced by chemotherapy used in the treatment of Bangladeshi breast cancer patients. A total of 200 and 56 patients with invasive breast cancers were recruited from different public and private hospitals of Bangladesh of which 117 patients received neoadjuvant chemotherapy to examine the response as well as the toxicity, and another 139 patients received adjuvant chemotherapy to evaluate only the toxicity. Genetic polymorphisms of the mentioned genes were detected by using Polymerase Chain Reaction Restriction Fragment Length Polymorphism (PCR RFLP). Patients carrying AG and AG plus GG genotype of GSTP1rs1695 were more likely to have a good response, whereas no association of ABCC4rs9561778 was found with the chemotherapy response. Patients carrying GT and GT plus TT genotypes of ABCC4rs9561778 were found to be associated with anemia, neutropenia, leukopenia, and gastrointestinal toxicities when compared with GG genotype whereas no association was found with thrombocytopenia. GSTP1rs1695 was not associated with any type of toxicities investigated. Our result indicates that GSTP1rs1695 polymorphism was strongly associated with the response of chemotherapy, whereas ABCC4rs9561778 polymorphism was significantly related with chemotherapy-induced toxicities.

Effects of organic extracts and their different fractions of five Bangladeshi plants on in vitro thrombolysis

BackgroundThe increasingly high incidence of ischemic stroke caused by thrombosis of the arterial vessels is one of the major factors that threaten people’s health and lives in the world. The present treatments for thrombosis are still unsatisfactory. Herbal preparations have been used since ancient times for the treatment of several diseases. The aim of this study was to investigate whether herbal preparations possess thrombolytic activity or not.MethodsAn in vitro thrombolytic model was used to check the clot lysis effect of the crude extracts and fractions of five Bangladeshi plant viz., Trema orientalis L., Bacopa monnieri L., Capsicum frutescens L., Brassica oleracea L. and Urena sinuata L. using streptokinase as a positive control and water as a negative control. Briefly, venous blood drawn from twenty healthy volunteers was allowed to form clots which were weighed and treated with the test plant materials to disrupt the clots. Weight of clot after and before treatment provided a percentage of clot lysis.ResultsUsing an in vitro thrombolytic model, different fractions of five Bangladeshi medicinal plants namely T. orientalis, B. monnieri, C. frutescens, B. oleracea and U. sinuata showed various range of clot lysis activity. Chloroform fractions of T. orientalis, B. monnieri, C. frutescens, B. oleracea and U. sinuata showed highest significant (P < 0.05 and P < 0.001) clot lysis activity viz., 46.44 ± 2.44%, 48.39 ± 10.12%, 36.87 ± 1.27%, 30.24 ± 0.95% and 47.89 ± 6.83% respectively compared with positive control standard streptokinase (80.77 ± 1.12%) and negative control sterile distilled water (5.69 ± 3.09%). Other fractions showed moderate to low clot lysis activity. Order of clot lysis activity was found to be: Streptokinase > Chloroform fractions > Methanol (crude) extract > Hydro-methanol fractions > Ethyl acetate fractions > n-hexane fractions > Water.ConclusionsOur study suggests that thrombolytic activity of T. orientalis, B. monnieri and U. sinuata could be considered as very promising and beneficial for the Bangladeshi traditional medicine. Lower effects of other extracts might suggest the lack of bio-active components and/or insufficient quantities in the extract. In vivo clot dissolving property and active component(s) of T. orientalis and B. monnieri for clot lysis could lead the plants for their therapeutic uses. However, further work will establish whether or not, chloroform soluble phytochemicals from these plants could be incorporated as a thrombolytic agent for the improvement of the patients suffering from atherothrombotic diseases.

Genetic polymorphisms of GSTM1, GSTP1 and GSTT1 genes and lung cancer susceptibility in the Bangladeshi population

ABSTRACT Objective To verify possible associations between polymorphisms of glutathione S-transferase Mu (GSTM1), glutathione S-transferase θ (GSTT1) and glutathione S-transferase Pi (GSTP1) genes and susceptibility to lung cancer. Methods A total of 106 lung cancer patients and 116 controls were enrolled in a case-control study. The GSTM1 and GSTT1 were analyzed using PCR while GSTP1 was analyzed using PCR-restriction fragment length polymorphism. Risk of lung cancer was estimated as odds ratio at 95% confidence interval using unconditional logistic regression models adjusting for age, sex, and tobacco use. Results GSTM1 null and GSTT1 null genotypes did not show a significant risk for developing lung cancer. A significantly elevated lung cancer risk was associated with GSTP1 heterozygous, mutant and combined heterozygous+mutant variants of rs1695. When classified by tobacco consumption status, no association with risk of lung cancer was found in case of tobacco smokers and nonsmokers carrying null and present genotypes of GSTM1 and GSTT1. There is a three-fold (approximately) increase in the risk of lung cancer in case of both heterozygous (AG) and heterozygous+mutant homozygous (AG+GG) genotypes whereas there is an eight-fold increase in risk of lung cancer in cases of GG with respect to AA genotype in smokers. Conclusions Carrying the GSTM1 and GSTT1 null genotype is not a risk factor for lung cancer and GSTP1Ile105Val is associated with elevated risk of lung cancer.

Phytochemical screenings, thrombolytic activity and antimicrobial properties of the bark extracts of Averrhoa bilimbi

Article history: Received on: 05/02/2013 Revised on: 21/02/2013 Accepted on: 01/03/2013 Available online: 30/03/2013 In this present study, the bark extracts of Averrhoa bilimbi were subjected to the thrombolytic activities were assessed by using human erythrocyte and the results were compared with standard streptokinase (SK). On the other hand, bark extracts of A. bilimbi revealed moderate antibacterial activity against some microorganisms used in the screening. Preliminary phytochemical investigation suggested the presence of flavonoids, saponins and alkaloids.

Evolution of selective COX-2 inhibitor from Alangium salvifolium: an in silico approach -

Pain and inflammation are linked with a number of pathological conditions. Several studies are in progress worldwide to find natural healing agents with better safety profile. Our current study is aimed to evaluate Alangium salvifolium (family: Alangeaceae) derived analgesic compounds for therapeutic drug discovery by computational approach. Literature based studies are used to explore the compounds of A. salvifolium. Ligands are prepared by following the appropriate procedures and finally in silico molecular docking analysis performed by GOLD 4.2. After post docking analysis salviifosides A of Alangium salvifolium is found to have interaction on COX-2 protein by obtaining highest fitness score 50.64 and molecular interaction suggests that it could be a potent anti-inflammatory compound and it may be worth for further clinical trials.

Molecular docking analysis of known flavonoids as duel COX-2 inhibitors in the context of cancer

Cyclooxygenase-2 (COX-2) catalyzed synthesis of prostaglandin E2 and it associates with tumor growth, infiltration, and metastasis in preclinical experiments. Known inhibitors against COX-2 exhibit toxicity. Therefore, it is of interest to screen natural compounds like flavanoids against COX-2. Molecular docking using 12 known flavanoids against COX-2 by FlexX and of ArgusLab were performed. All compounds showed a favourable binding energy of >-10 KJ/mol in FlexX and > -8 kcal/mol in ArgusLab. However, this data requires in vitro and in vivo verification for further consideration.

Molecular docking and analgesic studies of Erythrina variegata׳s derived phytochemicals with COX enzymes.

Secondary metabolites from plants are a good source for the NSAID drug development. We studied the analgesic activity of ethanolic extract of Erythrina variegata L. (Fabaceae) followed by molecular docking analysis. The analgesic activity of Erythrina variegata L. is evaluated by various methods viz., acetic acid-induced writhing test, hot plate and tail immersion test. Subsequently, molecular docking analysis has been performed to identify compounds having activity against COX-1 and COX-2 enzymes by using GOLD docking fitness. The result of preliminary phytochemical screening revealed that the extract contains alkaloids and flavonoids. In analgesic activity tests, the extract at the doses of 50, 100 and 200 mg/kg body weight (b.w.) produced a increase in pain threshold in a dose dependent manner. In acetic acid induced writhing test, the inhibitory effect was similar to the reference drug diclofenac sodium. The extract showed 18.89% writhing inhibitory effect at the dose 200 mg/kg b.w., whereas diclofenac sodium showed 79.42% inhibition of writhing at a dose of 10 mg/kg b.w. The results of tail immersion and hot plate test also showed potential analgesic activity of the extract which is also comparable to the standard drug morphine (5 mg/kg b.w.). Docking studies shows that phaseollin of Erythrina variegata L. has the best fitness score against the COX-1 which is 56.64 and 59.63 for COX- 2 enzyme. Phaseollin of Erythrina variegata L. detected with significant fitness score and hydrogen bonding against COX-1 and COX-2 is reported for further validation.

Antidiarrheal and antinociceptive activities of ethanol extract and its chloroform and pet ether fraction of Phrynium imbricatum (Roxb.) leaves in mice

Abstract Background: The objective of the study was to evaluate the antidiarrheal and antinociceptive activities of ethanol extract and its chloroform and pet ether fraction of Phrynium imbricatum (Roxb.) leaves in mice. Methods: In the present study, the dried leaves of P. imbricatum were subjected to extraction with ethanol, and then it was fractioned by chloroform and pet ether solvent. Antidiarrheal effects were tested by using castor oil-induced diarrhea, castor oil-induced enteropooling, and gastrointestinal transit test. Antinociceptive activity was evaluated by using the acetic acid-induced writhing test and formalin-induced paw licking test. Results: The standard drug loperamide (5 mg/kg) showed significant (p<0.001) inhibitory activity against castor oil-induced diarrhea, in which all the examined treatments decreased the frequency of defecation and were found to possess an anti-castor oil-induced enteropooling effect in mice by reducing both weight and volume of intestinal content significantly, and reducing the propulsive movement in castor oil-induced gastrointestinal transit using charcoal meal in mice. The results showed that the ethanol extract of P. imbricatum leaves has significant dose-dependent antinociceptive activity, and among its two different fractions, the pet ether fraction significantly inhibited the abdominal writhing induced by acetic acid and the licking times in formalin test at both phases. Conclusions: These findings suggest that the plant may be a potential source for the development of a new antinociceptive drug and slightly suitable for diarrhea, as it exhibited lower activity. Our observations resemble previously published data on P. imbricatum leaves.