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Journal of Pharmaceutical Negative Results
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How to select appropriate statistical test?
October-December 2010, 1(2):61-63
  52,142 5,047 3
Rimonabant: Boom to ban
Suyog S Jain, Vitthal B Karande, Karuna B Ramteke, Girish T Raparti
July-December 2011, 2(2):45-50
Rapidly rising prevalence of obesity and health care cost of its complications necessities need for highly efficacious and safe antiobesity drugs. As most old antiobesity drugs had moderate efficacy, severe toxicity and some of them very costly. Rimonabant, CB1 receptor antagonist was introduced with high expectations. Rimonabant has multiple beneficial effects, apart from significant weight loss it increases HDL and reduces triglycerides, Hb A 1C level, prevalence of metabolic syndrome. This wide spectrum of effects helps in comprehensive management of obesity and associated complications. Cost of rimonabant (generic Rs.5-8 per tablet) is also much lesser than the only other commonly used antiobesity drug orlistat around Rs. 40 per tablet. During trials rimonabant apart from nausea had neuropsychiatric side effects. EMEA approved rimonabant in June 2006 with concern over its psychiatric side effects. In 2007 EMEA contraindicated rimonabant in patients of depression or taking antidepressants. Further analysis in 2008 concluded that the incidence of psychiatric side effects was higher in clinical practice compared to controlled trials also few cases of suicide became a major safety concern, finally leading to suspension of its sale by EMEA in Oct 2008. USFDA never approved rimonabant over safety concerns, while India banned it shortly thereafter as precautionary measure. Present paper deals with the various events during the rapid rise and fall of rimonabant which was widely considered as blockbuster diet pill but was suspended over serious neuropsychiatric side effects.
  6,292 9,202 -
Absence of anthelmintic activity of hydroalcoholic leaf extracts of Artabotrys hexapetalus (Linn.f)
M Vasundhara, YP Karthik, KR Anjali, C Chithra, Priyanka Gupta, C Roopa
January-December 2014, 5(1):1-3
Objective: To study the anthelmintic activity of Artabotrys hexapetalus (Linn.f) leaves. Materials and Methods: The extraction was made using the hydroalcohol with soxhlet extraction system. The hydroalcoholic extract of varying concentration was used for conducting anthelmintic activity (12.5, 25, 50 and 100 mg/ml). Eudrilus eugeniae (African adult earthworm) was used as the test organism. Result: The time of paralysis and death of the earthworms, the positive control (albendazole) was more effective and no effect was shown by the hydroalcoholic extract of varying concentrations. Conclusion: Hydroalcoholic extract of Artabotrys hexapetalus, didn't show any anthelmintic activity at the concentration of 12.5, 25, 50 and 100 mg/ml.
  4,295 8,939 -
Lack of brine shrimp lethality and hemagglutination activity in Grewia asiatica Linn
Abidah Parveen, Mohammad Irfan, Muhammad Saleem Jilani, Kashif Wasim, Mehwish Kiran, Fida Muhammad
January-December 2013, 4(1):1-4
Objective: To investigate the brine shrimp lethality and hemagglutination activity of the fruit, stem bark and leaves of Grewia asiatica L. (Family: Tiliaceae). Materials and Methods: The crude ethanolic extracts and fractions of the fruit, stem bark, and leaves were subjected to cytotoxic assay using brine shrimps and were also investigated for hemagglutination activity. Results: Brine shrimps survived easily and hemagglutination activity was not observed. Conclusions: The fruits, leaves and stem bark of G. asiatica have insignificant brine shrimp lethality and hemagglutination activity was found to be absent.
  3,390 9,581 1
Prospective on publishing negative results
Subramani Parasuraman
January-December 2015, 6(1):1-1
  3,499 8,338 -
No evidence of antiseptic properties and low toxicity of selected Aloe species
L Mpala, G Chikowe, IE Cock
July-September 2010, 1(1):10-16
Background and Aim: Closely related plant species often share similar secondary metabolites and bioactivities and are therefore good targets for bioactivity testing when one or more species within a genus are known to possess therapeutic properties. The genus Aloe has a long history of medicinal usage in many areas of the world. Many species are known to have therapeutic properties, several species of which have well-established antibacterial bioactivities. The current studies examine the toxicity of several Aloe species and their ability to inhibit bacterial growth and compare them to the most extensively studied species, Aloe barbadensis, which has well-established antibacterial bioactivities. Results: A. barbadensis methanolic extract displayed broad spectrum antibacterial activity, inhibiting the growth of 8 of the 14 bacteria tested (57%). It was effective against both Gram-positive and Gram-negative bacteria, inhibiting the growth of 4 of 4 Gram-positive bacteria (100%) and 4 of 10 Gram-negative (40%) bacteria tested, respectively. In contrast, Aloe elgonica, Aloe pruinosa, Aloe chabaudii, Aloe daiyana, Aloe marlothi and Aloe vryheidensis all showed no antibacterial activity toward any of the bacteria tested. All of the Aloe species displayed low toxicity similar to that of the A. barbadensis control. A. daiyana was the most toxic of the Aloe species tested with 24, 48 and 72 hours LC50 values of 1018.2, 517.0 and 405.7 ΅g/ml, respectively. Conclusions: Despite their close taxonomic relationship, A. elgonica, A. pruinosa, A. chabaudii, A. daiyana, A. marlothi and A. vryheidensis do not have the same antibacterial medicinal potential as A. barbadensis, but may still have other similar toxicity-related bioactivities. Testing against protozoa, fungi, virus and tumor cells is required to determine if this is the case.
  10,505 672 4
Negative regulation of glucose uptake by Costus pictus in L6 myotube cell line
Anil Pareek, Manish Suthar, Ashok Godavarthi, Manoj Goyal, Vijay Bansal
July-September 2010, 1(1):24-26
The leaf of Costus pictus D. Don is considered as an antidiabetic in folklore medicine and is known to reduce the blood sugar, similar to insulin. The aim of this study is to investigate the effect of ethanolic extract of C. pictus leaf on glucose uptake by L6 myotube cell line (skeletal muscle cells) involved in glucose utilization. Ethanolic extract of C. pictus leaf was analyzed to study GLUT4 translocation and glucose uptake activity, but it has no direct peripheral action at 300 μg/ml dose comparable with insulin and metformin. The glucose uptake was not enhanced by the extract of C. pictus leaf.
  10,156 947 4
Lack of antiglycation activity of fresh juice of whole plant of Enicostema axillare (Lam.) Raynal
WD Ratnasooriya, K.I.W.K Somarathna, G.A.S Premakumara, E.R.H.S.S Ediriweera
July-December 2011, 2(2):55-57
Objective: To investigate the antiglycation potential of fresh juice of whole plant of Enicostema axillare (Lam.) Raynal. in vitro. Materials and Methods: Antiglycation activity of fresh juice of whole plant was determined in vitro using five concentrations (25, 50, 100, 200, and 400 μg/ml) by determining their ability to inhibit the formation of advanced glycation endproducts in a bovine serum albumin / glucose system using fluorescence spectroscopy. Results: There is no antiglycation activity in vitro of fresh juice of E. axillare plant. Conclusion: It is unlikely that impairment of diabetic complications by E. axillare whole plant juice as claimed by ayurvedic and traditional physicians is mediated via antiglycation activity.
  9,071 1,776 1
Insignificant anti-acne activity of Azadirachta indica leaves and bark
Pratibha Nand, Sushma Drabu, Rajinder K Gupta
January-December 2012, 3(1):29-33
Background and Aim: Azadirachta indica has a long history of medicinal usage in skin ailments due to its antibacterial and anti-inflammatory properties. The present study was undertaken to explore the potential of the leaves and bark of Azadirachta indica in the treatment of acne. Materials and Methods: Monographic analysis of the plant was carried out, followed by the phytochemical screening of the sequential extracts of leaves and bark of Azadirachta indica. The results indicated presence of alkaloids, flavonoids, saponins, terpenes, and tannins. Gas chromatography-mass spectrometry (GC/MS) analysis of the test extracts indicated the presence of many phytoconstituents in dichloromethane and methanolic extracts namely stigmasterol, nimbiol, sugiol, 4-cymene, α-terpinene terpinen-4-ol, and vitamin E. The test extracts were evaluated against acne causing bacteria, namely Staphylococcus aureus (MTCC 96), Staphylococcus epidermidis (MTCC 2639), and Propionibacterium acnes (MTCC *1951), for their in vitro antimicrobial activity, using agar disc diffusion method. Results: Dichloromethane and methanolic extracts of Azadirachta indica showed very little activity against S. aureus and S. epidermidis, but did not show any antimicrobial activity against P. acnes. Conclusion: Despite possessing antibacterial properties, Azadirachta indica showed insignificant effect against acne causing bacteria.
  8,737 1,033 1
Negative effect of Alocasia macrorrhizos on the lipid profile in hyperlipidemic rats
Ramya , SD Ullal, R Maskeri, MS Pradeepti, Habeeba Umma, S Rajeshwari
January-December 2012, 3(1):9-12
Introduction: Currently, there is considerable interest in the development of lipid-lowering agents from natural products. The purpose of this study was to evaluate the hypolipidemic activity of hydroalcoholic extract of leaves of Alocasia macrorrhizos (AM), which is known to have anti-oxidant activity. Materials and Methods: Cholesterol-rich high-fat-diet was used to induce hyperlipidemia. Rats were randomly assigned to five groups of six rats each. Groups 1 and 2 served as normal and high-fat-diet-fed control, respectively. Group 3 received the standard drug, atorvastatin, while groups 4 and 5 received AM 250 and 500 mg/kg, respectively. High-fat-diet was fed for 45 days and treatment/vehicle was administered during the latter 30 days, following which blood samples of anaesthetized rats obtained by cardiac puncture were sent for lipid profile. Results: High-fat-diet significantly increased (P < 0.05) all the parameters of lipid profile compared to group 1. Atorvastatin treatment significantly reduced total cholesterol (TC), LDL-C, VLDL-C (P < 0.001), and triglyceride (P < 0.05), however, there was no significant change in HDL-C compared to group 2. AM at both the doses significantly reduced triglyceride and VLDL-C levels compared not only to group 2, but also to group 3 (P < 0.05). There was no change in TC and HDL-C levels, however, there was a significant dose related rise in the LDL-C level in the AM-treated groups compared to group 2 (P < 0.05 at 250 mg/kg, P < 0.001 at 500 mg/kg). Conclusion: The hydroalcoholic extract of leaves of Alocasia macrorrhizos at the dose of 250 and 500 mg/kg in rats significantly reduced triglyceride and VLDL-C levels; however, it increased LDL-C. Hence, it may not be suitable as a lipid-lowering agent.
  3,942 5,175 -
Anticonvulsant activity of Passiflora incarnata: No role of chrysin
Bhupinder Singh, Awanish Mishra, Rajesh Kumar Goel
July-December 2011, 2(2):51-54
The earlier studies on Passiflora incarnata have pointed out the possible role of chrysin for its anticonvulsant activity. But role of chrysin in anticonvulsant property of P. incarnate seems to be controversial due to its poor bioavailability reported by different studies. Therefore, this study was designed to investigate the role of chrysin in anticonvulsant property of different extracts of P. incarnata used for medicinal purpose, viz. aqueous (PIAE), hydroethanolic (PIHE), and methanolic extracts (PIME). These extracts were prepared from dried leaves of P. incarnata using water, methanol, and 50% ethanol to obtain PIAE, PIME, and PIHE, respectively. The extracts were standardized with reference to chrysin by HPLC-UV method. Different doses (150, 300 and 600 mg/kg; i.p.) of PIAE, PIME, PIHE, and chrysin (1 mg/kg) were administered 30 min before the PTZ injection (75 mg/kg) to evaluate anticonvulsant effect. HPLC estimation has shown the higher amount of chrysin present in PIME followed by PIAE and PIHE. Significant dose-dependent delay in onset of convulsions was observed in PIHE and PIAE treated mice when compared with PTZ convulsive mice, while PIME treatment has not shown delay in onset of convulsions. Chrysin (1 mg/kg, i.p.), as well, did not produce significant increment in onset of convulsions. These results revealed that PIME containing significant amount of chrysin lacks anticonvulsant effect, while PIAE and PIHE, with insignificant chrysin content, have shown significant anticonvulsant effect. Thus, this study suggests that chrysin is not responsible for anticonvulsant effect of P. incarnata.
  6,253 2,718 2
Treatment with N-acetylcysteine does not alter blood glucose levels and the oxidative stress status in diabetic rats
André Valle de Bairros, Miguel Roehrs, Gianine Ribeiro, Fernando de Freitas, Ana Paula Moreira, Raquel Tonello, Cinthia Mazzanti, Mirna Leal, Vera Maria Morsch
January-December 2013, 4(1):5-12
Objectives: To verify the contribution of N-acetylcysteine (NAC) as an antioxidant drug in the therapy of diabetes, helping to reduce the deleterious effects resulting from oxidative stress associated with the hyperglycemic state. Materials and Methods: The animals were divided into normal (saline, 25 mg/kg NAC, and 75 mg/kg NAC) and diabetic rats (saline, 25 mg/kg NAC, and 75 mg/kg NAC) with five rats per group, and were treated or four weeks. Diabetes induction was performed by intraperitoneal injection of alloxan after fasting for 12 hours. Subsequently, glucose solution was used to promote wear of the pancreatic beta cells. Blood parameters such as glucose, glycated hemoglobin, hepatic and renal biomarkers, and butyrylcholinesterase activity were determined by commercial kits. Catalase, glutathione peroxidase, and superoxide dismutase activities were measured using spectrophotometric techniques, while glutathione and malondialdehyde levels were determined by chromatographic techniques. Results: NAC had no significant differences on glycemic, hepatic, renal, and oxidative stress biomarkers. Superoxide dismutase activity was significantly higher ( P < 0.05) in diabetic rats treated with NAC compared to the diabetic saline group, while butyrylcholinesterase activity was significantly lower ( P < 0.05) in the same groups. There was a negative correlation between superoxide dismutase and butyrylcholinesterase activities. Conclusion: NAC supplementation did not re-establish the antioxidant system and consequently the deleterious effects of diabetes did not decrease. Diabetic groups that received NAC demonstrated that superoxide dismutase activity was indirectly linked to the levels of butyrylcholinesterase. More studies are necessary to investigate the action of NAC on superoxide dismutase and butyrylcholinesterase activities in the diabetic state.
  6,677 2,242 2
Influence of solvents on the crystal habit and properties of rofecoxib and celecoxib: No evidence of polymorphism
MK Raval, PR Sathesh Babu, J Thimmasetty, RK Parikh, NR Sheth, C.V.S. Subrahmanyam
October-December 2010, 1(2):40-50
Background: In many cases, drugs can exist in more than one crystalline form; the phenomenon is known as "polymorphism." Though the polymorphs are chemically identical, they exhibit different physicochemical properties, viz., melting point, solubility, X-ray diffraction pattern, etc., which further affect the biological properties of drugs. The purpose of this work was to study the effect of solvents on crystallization, solubility and dissolution of rofecoxib and celecoxib. Materials and Methods: The crystals were prepared by using different solvents. The melting point, solubility, dissolution, Fourier-transformed infrared (FT-IR), X-ray diffraction (XRD), differential scanning calorimetry (DSC) and scanning electron microscopy (SEM) studies were carried out to confirm the polymorphism in drugs. Result: The results indicate that the crystals obtained from different solvents exhibited different physicochemical properties. Though FT-IR and XRD gave an indication of different crystal morphs, DSC proved absence of any polymorphic behavior in the crystals of rofecoxib and celecoxib. Conclusion: Crystals having the desired physicochemical properties may be obtained by selecting solvents of specific polarities.
  7,207 885 5
Propylthiouracil in treating psoriasis, a promise that failed: A hospital-based prospective study of propylthiouracil in the treatment of psoriasis
Murugaiyan Rangaraj, Kaliaperumal Karthikeyan
January-December 2016, 7(1):1-3
Introduction: Psoriasis is a common skin disorder with no cure and definite treatment options. Propylthiouracil (PTU), an antithyroid drug, has been found to be effective in treating psoriasis in certain studies. This prompted us to conduct a study to assess the effectiveness of PTU in treating patients with psoriasis. Aims: The primary objective of our study was to assess the efficacy of PTU as a safe and effective agent in the management of psoriasis. Settings and Design: This study was a clinical prospective study conducted over a period of 3 months. Materials and Methods: Thirty one patients with psoriasis and those fulfilling the inclusion criteria were treated with PTU (100 mg thrice a day) and topical emollient, and were followed up for 12 weeks. Psoriasis Area Severity Index (PASI) at the baseline and at the end of the study were compared. Patients who attained PASI score 50 were considered to respond to the treatment. Statistical Analysis Used: Mean values of variables. Results: The mean PASI score at the beginning of the treatment with PTU was 17.6. The mean PASI score at the end of the study was 16.06. Conclusions: We found PTU to be ineffective in reducing both the symptoms and severity of psoriasis. It is also intriguing to note that PTU, which was found to be effective in treating psoriasis almost two decades ago, has never been used widely in practice. Probably, this bears testimony to the fact that PTU is not as effective as it was promised to be.
  4,337 3,738 -
Absence of antimicrobial activity of Euphorbia milii molluscicidal latex
Eduardo C Oliveira-Filho, Bianca F. G. Z. Alves, Jacyara C Lopes, Valdi L Tutunji
January-December 2012, 3(1):13-15
Introduction : Euphorbia milii latex has been used as herbal medicine and proved to be a potent plant molluscicide. Materials and Methods : The susceptibility of Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa to E. milii molluscicidal latex was evaluated by assays in the agar well diffusion method and tubes dilution, to determine the minimal inhibitory concentration and minimal bactericidal concentration. Results : Latex in natura (fresh) and lyophilized in a maximum viable concentration of 100 mg/L did not show any inhibitory effect on the growth of the bacterial strains tested. Conclusion : Although it has been effective as a molluscicide, this latex presented a total absence of antimicrobial activity in the two forms and concentrations tested.
  5,183 2,580 -
Absence of anxiolytic activity of Sarcocephalus latifolius fruit extract
David Arome, Chinedu Enegide, Solomon Fidelis Ameh, Amarachi Agbafor, Esenju Rose Mbonne, Itinegbedia Monica
January-December 2014, 5(1):4-7
Introduction: The use of pharmacological agents in the treatment of anxiety disorders have fallen out of favor as their unwanted side-effects have become evident. These presenting challenges call for an inward look into harnessing the full potential of medicinal plants that abound around us. Aim: This study aimed at evaluating the anxiolytic activity of ethanolic fruit extract of Sarcocephalus latifolius in mice. Materials and Methods: The prepared extract at 200, 400, and 600 mg/kg as well as 2.5 mg/kg of diazepam reference standard was administered orally. Anxiolytic activity of the extract was explored using elevated plus-maze and open-field models. Result: In the elevated plus-maze, the extract possessed insignificant (P > 0.05) anxiolytic effect by decreasing the time spent in open arms and entries into the open arms. However, the time spent in the closed arms increased significantly in the extract treated groups compared to the reference standard. In the open-field model, no significant (P > 0.05) locomotor activity was observed in the extract groups. The number of locomotion was less in the extract groups compared the reference standard having the highest locomotive activity. Furthermore, there were reduction in the number of rearing at extract doses of 400 and 600 mg/kg compared with the normal saline and reference standard. Conclusion: The results of this study showed that the ethanolic fruit extract of S. latifolius lack anxiolytic activity.
  4,897 2,346 2
Effort toward the single pot synthesis of 6-(Biphenyl-4-yl)-2-[2-(indol-1-yl)ethyl]-4,5-dihydropyridazin-3(2H)-one from 6-(Biphenyl-4-yl)-2-[2-(indol-1-yl)ethyl]-4,5-dihydropyridazin-3(2H)-one
Mohammad Asif, Anita Singh, Lakshmayya
July-December 2011, 2(2):69-72
Background: Many synthetic heterocyclic compounds are known to have different biological activities. Pyridazine and its derivatives are the important six membered heterocyclic compounds containing two N-hetero atoms. The pyridazine moiety is an important structural feature of many biologically active compounds. Pyridazine derivatives show diverse pharmacological properties. Aims and Objectives of the Study: The goal of this study, Pyridazine hold considerable interest relative to the preparation of organic intermediates and physiologically active compounds also. On the basis of its important in reported literature, we synthesized the 6-(Biphenyl-4-yl)-2-[2-(indol-1-yl)ethyl]-4,5-dihydropyridazin-3(2H)-one from 6-(Biphenyl-4-yl)-2-[2-(indol-1-yl)ethyl]-4,5-dihydro pyridazin-3(2H)-one in single step or pot reaction. Results : The important Observations and concrete implications of the study. The result showed that the compound 6-(Biphenyl-4-yl)-2-[2-(indol-1-yl) ethyl]-4,5-dihydropyridazin-3(2H)-one was not prepared by this method. The synthesis of compound has been confirmed by the spectral analysis namely IR, 1H NMR and Mass spectroscopy.
  6,396 434 -
Influence of some hydrophilic polymers on dissolution characteristics of furosemide through solid dispersion: An unsatisfied attempt for immediate release formulation
MK Raval, DU Prajapati, SM Varma, MA Khodifad, JM Patel, NR Sheth
October-December 2010, 1(2):29-34
Background: The objective of the present investigation was to enhance dissolution characteristics of water insoluble drug, furosemide (FRMD), by solid dispersion in various hydrophilic carriers. Materials and Methods: The solid dispersions were prepared by solvent evaporation technique using urea and Hydroxy Propyl Methyl Cellulose (HPMC E50 LV). Physical mixtures of drug with above-mentioned polymers were also prepared. Phase solubility studies were performed for drug in the presence of excipients in different ratios. The formulations were evaluated for drug content, in vitro dissolution, Fourier transform infrared (FT-IR) and differential scanning calorimetry (DSC). Similarity factor (f2) was calculated for comparison between dissolution of pure drug and drug-polymer physical mixtures with solid dispersions. Results: Phase solubility studies indicated linear increase in the drug solubility with increase in carrier concentration. In vitro release studies revealed that dissolution characteristic of FRMD was improved by solid dispersion technique. All the preparations of FRMD exhibited significant improvement in its dissolution profiles. Solid dispersion of FRMD with HPMC E50 LV exhibited the highest rate and extent of dissolution. Optimized batches of solid dispersions of both the carriers were characterized by FT-IR and DSC analysis, which indicated absence of major interactions between FRMD and carriers. Conclusion: Solid dispersion technique is one of the finest techniques to improve dissolution of poorly soluble drugs.
  5,823 746 -
Nonprotective role of losartan in cisplatin-induced nephrotoxicity in ovariectomized rat model treated with estradiol
Fereshteh Ghadirian, Mehdi Nematbakhsh, Shahla Roozbehani, Safoora Mazaheri, Ardeshir Talebi, Zahra Pezeshki, Farzaneh Ashrafi
January-December 2015, 6(1):2-6
Objective: The aim was to study the role of losartan on cisplatin (CP)-induced nephrotoxicity in an estradiol replacement rat model. Materials and Methods: Forty-seven female Wistar rats were ovariectomized and divided into seven groups. Groups 1 and 2 were treated with placebo (sesame oil) on a weekly basis for 4 weeks, and then they received saline or CP (2.5 mg/kg/day) for the next 7 days, respectively. Group 3 received estradiol (250 μg/kg/week) for 4 weeks, and then treated with losartan (10 mg/kg/day) for the next 10 days while from day 3; they also received CP for 7 days. Group 4 had treatment regimen the same as Group 3, except saline instead of losartan. Groups 5 and 6 were treated similar to Groups 3 and 4, respectively, but the dose of estradiol was doubled. Finally, Group 7 was treated as Group 3 except vehicle instead of estradiol. At the end of the experiment, blood samples were obtained to measure blood urea nitrogen (BUN), creatinine (Cr), nitric oxide metabolite (nitrite) and malondialdehyde (MDA). The kidney tissues were also subjected to pathology investigations. Results: Cisplatin significantly increased the serum level of BUN, Cr, and MDA (P < 0.05). CP also increased kidney weight (KW) and kidney tissue damage score (KTDS), and decreased bodyweight significantly (P < 0.05). There is a significant difference in KTDS, weight changes and serum level of MDA between positive control groups compared with the groups received combination of losartan and CP (P < 0.05). Conclusions: It seems that the estrogen could promote CP-induced nephrotoxicity. Losartan also did not intensify CP-induced nephrotoxicity. Accordingly, supplementation of losartan to attenuate CP-induced nephrotoxicity in ovariectomized model treated with estradiol is not suggested.
  3,886 2,392 1
Rofecoxib-induced deleterious effects escape detection by organismal performance assays
Shannon M Gaukler, James S Ruff, Linda C Morrison, Wayne K Potts
January-December 2016, 7(1):4-11
Background: Organismal performance assays (OPAs) are a unique method of toxicity quantification used to assess the safety of potentially toxic compounds such as pharmaceuticals. OPAs utilize genetically diverse wild mice (Mus musculus) housed in large seminatural enclosures wherein exposed individuals compete directly with controls for resources. Previously, OPAs have been successful in detecting adverse effects in mice that were exposed to paroxetine. Here, we further test OPAs' utility in pharmaceutical safety assessment by testing OPAs with rofecoxib, a drug with known adverse effects on humans. Materials and Methods: We exposed mice to rofecoxib (~37.5 mg/kg/day) during gestation and into early adulthood. Exposure ceased when individuals were released into enclosures. Five independent populations were established and rofecoxib-exposed individuals (n = 58) competed directly with control individuals (n = 58) over 28 weeks. Organismal performance was determined by quantifying reproduction, survival, and male competitive ability. Results: In enclosures, rofecoxib-exposed males had equal reproduction, survival, and competitive ability. Rofecoxib-exposed females had equal survival compared to controls but experienced 40% higher reproductive output. Conclusions: The adverse health effects of rofecoxib seen in humans escaped detection by OPAs, just as they had during traditional preclinical assays. These results may be explained by the exposure design (in the enclosures, all animals were on the control diet), the relatively short duration of exposure, species differences, or because the health benefits of the drug negated the side effects. Similar to numerous assays used in preclinical trials, OPAs cannot reveal all maladies, despite their demonstrated sensitivity in detecting cryptic toxicity from numerous exposures.
  4,556 1,685 2
Lack of the cytochrome P450 3A interaction of methanolic extract of Withania somnifera, Withaferin A, Withanolide A and Withanoside IV
Jay Savai, Alice Varghese, Nancy Pandita
January-December 2013, 4(1):26-32
Aims: Withania somnifera is widely employed as a rejuvenator and expected to promote physical health and increase longevity. The aim of the present research work was to evaluate Cytochrome P450 3A (CYP3A) interaction of Withania somnifera. Materials and Methods: In vitro CYP3A interaction of methanolic extract of Withania somnifera (WS) and its principal phytoconstituents: Withaferin-A (WA), Withanolide-A (WL-A) and Withanoside-IV (WS-IV) were investigated in rat and human liver microsomes. In vivo CYP3A interaction potential was investigated by administering methanolic extract of WS orally at a dose of 500 mg/kg in female Wistar rats. Sildenafil citrate was used to index the activity of CYP3A. Results: IC 50 values of methanolic extract of Withania somnifera, WA, WL-A, WS-IV were found to be 200 μg/ml, >20 μM, >64 μM and >64 μM for CYP3A both in rats and humans, respectively. When sildenafil citrate was orally co-administered with methanolic extract of WS and compared with orally administered sildenafil citrate alone, the area under plasma concentration time (AUC) curve and C max did not significantly differ as compared to the group which received rifampicin orally (positive control). Conclusions: Results suggested that methanolic extract of WS, WA, WL-A, WS-IV showed no in vitro CYP3A inhibition in rats and humans. Methanolic extract of WS did not significantly alter the pharmacokinetics of sildenafil citrate in rats; indicating its safety when co-administered with other drugs that are substrates of CYP3A. Thus the results indicate the lesser likelihood of drug herb interactions when concomitantly administered with CYP3A substrates.
  5,492 490 2
Beta vulgaris : A dearth of antidepressant activity in mice
Ashok Agrawal, Sunil Bavaskar, Pankaj Salunkhe, Nadeem Manyar, Dnyaneshwar Kale, Pravin Kawtikwar
October-December 2010, 1(2):55-57
The present study was undertaken to investigate antidepressant activity of ethanolic extract of Beta vulgaris [BV], by using forced swim test [FST] and tail suspension test [TST] in mice. Imipramine [10 mg/kg, i.p.] used as the standard drug significantly decreased immobility time in both TST and FST, while BV [50 and 100 mg/kg, i.p.] significantly increased immobility time in TST and FST. This suggests that BV has depressant activity and not antidepressant activity.
  5,388 435 -
Insignificant anticancer activity of novel substituted pyrimidine derivatives
Anshu Chaudhary, Pramod Kumar Sharma, Shiv Jee Kashyap, Jitendra Kumar Gupta, Rupesh Dudhe, Prabhakar Verma
July-December 2011, 2(2):62-68
Background: Pyrimidine and fused pyrimidine derivatives play an important role in therapeutic strategies. It is known to be most prominent structures found in nucleic acid, including uracil, thymine, cytosine, adenine, and guanine, which are fundamental building blocks for deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). Materials and Methods: A series of 3-[2-amino-6-(substituted)-pyrimidin-4-yl]-6-(substituted)-2H-chromen-2-one derivatives were prepared by reacting salicylaldehyde with ethylacetoacetate in the presence of piperidine by Knoevenagel reaction as a starting material. The chemical structures were confirmed by means of FTIR (Fourier Transform InfraRed Spectrophotometer-8400S), 1H NMR, and elemental analysis. The data of these synthesized compounds were submitted to National Institute of Health, USA, under the drug discovery program of NCI (National Cancer Institute) and screened for anticancer activity at a single high dose (10−5 M) in full NCI 60 cell lines. Results: Unfortunately, the selected compounds have not shown any potent significant anticancer activity in the NCI 60 cell line screening. Conclusion: The compound (T2) found to be most efficient anticancer activity with selective influence on breast cancer cell lines, especially on MCF7 cell line with a growth percentage of 33.63.
  4,934 804 3
Unsatisfied processing conditions in making ifosfamide nanostructured lipid carriers: Effects of various formulation parameters on particle size, entrapment efficiency, and drug loading capacity
Ramaiyan Velmurugan, Subramanian Selvamuthukumar
January-December 2014, 5(1):8-12
Introduction: The objectives of the present investigation were to develop an optimized formulation of ifosfamide (IF) nanostructured lipid carrier (NLC) to sustain the release, to overcome the instability of the drug in an acidic environment during oral administration, drug leakage during storage, drug expulsion, and low drug loading (DL). Materials and Methods: The IF NLC was prepared by solvent diffusion technique. Response surface methodology was applied to optimize the formulation. Drug/lipid ratio, organic/aqueous phase ratio, and concentration of surfactant were considered as the formulation variables that mainly affects the particle size (PS), entrapment efficiency (EE) and DL of the NLC. A total of 20 sets of formulations were performed with different ratios of drug/lipid, organic/aqueous phase volume and various concentration of the surfactant. The formulation was evaluated for PS, EE, and DL, differential scanning calorimetry, Fourier transform infrared and in vitro dissolution. Results: Increasing the aqueous phase volume results in an increase of EE and a decrease in loading capacity. PS also decreases to extent. Increasing the lipid concentration, EE increases and as well the PS. An increase in the concentration of the surfactant resulted in a decrease in PS and a slight increase in encapsulation efficiency and loading capacity. Conclusion: The positive impact on the response variables (PS, EE and DL capacity) of the formulation of IF NLC would be obtained only if the processing conditions could be followed.
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Insignificant antifungal activity of plant extracts on Malassezia furfur
Sreelatha Gopalakrishnan Lalitha, Lakshmeesha Thimappa Ramachandrappa, Soumya Krishnamurthy, Jayashree Basavaraju, Sharmila Thirumale
January-December 2016, 7(1):16-20
Objective: The aim of present study was to investigate the antimalassezial potential of the selected plant extracts known to possess medicinal values. Materials and Methods: The crude extracts of five botanicals were evaluated against Malassezia furfur. The dried and pulverized plant material was extracted with water and also successively extracted with hexane, chloroform, and methanol, using the Soxhlet apparatus. The antimicrobial activity assay was done by disk diffusion and 96-well plate microdilution method. Results: The results point toward the fact that all the tested extracts extracted in solvents of different polarities exhibited no antifungal activity. Conclusion: The tested extracts did not have, or had too little, antifungal activity to be used as a promising source of novel antimicrobial substances against M. furfur.
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