Behavioral and biochemical characterization of elevated “I-maze” as animal model of anxiety

AbstractThe elevated I-maze is a modification of the elevated plus-maze model of anxiety in mice. The design of I-maze comprises a straight wooden passage, resembling the English letter “I,” divided equally into three areas; two enclosed areas (close arms) at both ends of the “maze” and an open area in the center of two enclosed areas. The I-maze completely avoids the central platform of elevated plus-maze, removing any ambiguity in time spent on central platform and allowing uninterrupted animal exploration. In this model, diazepam (1 mg/kg) and gabapentin (10 mg/kg) significantly increased the percentage of time spent in the open areas (%TO) and the number of unprotected head dips (uHDIPS), and reduced the number of protected head dips (pHDIPS) and stretch attend postures (SAP) from close to open arm. Similarly, fluoxetine (5 mg/kg) significantly increased %TO and uHDIPS, and significantly decreased SAP from close to open arm, but it did not have any significant effect on pHDIPS. The 5-HT3 receptor antagonist, ondansetron (0.1 mg/kg), did not produce any significant change in all the behaviors, observed, as compared to vehicle-treated control mice. On the other hand, the anxiogenic agent, caffeine (15 mg/kg), did produce a significant decrease in %TO and uHDIPS, and significantly increased pHDIPS and SAP from close to open arm. Mice confined in open area of I-maze bring the relevant biochemical changes associated with anxiety behavior, showing significant increase in the levels of plasma nitrate and plasma corticosterone. These data indicate that a combination of novel design of elevated I-maze and a detailed behavioral analysis provides a sensitive model for the measurement of anxiety

ATTENUATION OF ANTINOCICEPTIVE EFFECT OF MORPHINE IN DIABETIC MICE: NITRIC OXIDE OR INTERLEUKIN-2

Objective: The present study was designed to explore the mechanistic role of interleukin-2 in diabetes-induced decrease in the antinociceptive effect of morphine in mice. Role of interleukin-2 was investigated by employing cyclosporin, a interleukin-2 synthesis inhibitor. Methods: Diabetes was induced in mice by single intra peritoneal injection of Streptozotocin (200 mg/kg, i. p.). Nociceptive threshold in diabetic mice was measured by Rodent tail-flick test. Nitrite levels in the urine of mice were estimated by employing Greiss reagent. Results: A significant decrease in antinociceptive effect of morphine was observed in mice. Administration of cyclosporin (20 mg/kg, s. c., b. d.) in diabetic mice significantly increased antinociceptive effect of morphine in diabetic mice. However, administration of cyclosporin (20 mg/kg, s. c., b. d.) failed to significantly change the increased nitrite levels in diabetic mice.Conclusion: The present study indicates that interleukin-2 may be responsible for decrease in antinociceptive effect of cyclosporine. The study also indicates that the increase in levels of interleukin-2 is independent of an increase in nitrite levels. It may, therefore, be concluded that nitric oxide has no role in nociceptive changes made by interekin-2 in diabetic mice. Â

A NOVEL NON–RECEPTOR AND NON- GABAERGIC ANTIANXIETY-LIKE ACTIVITY OF FORSKOLIN: SYNERGY WITH DIAZEPAM

Objective: Clinical problems associated with the benzodiazepines like dependence, withdrawal or tolerance may lead to under use of substances based on gamma-amino butyric acid (GABA). Non-GABAergic and substances that elevate cyclic adenosine monophosphate (cAMP) have shown anti-anxiety activity. Therefore, present investigation aimed to explore a non-GABAergic mechanism and non-receptor mediated anti-anxiety activity of a cAMP elevating agent, forskolin.Methods: Elevated plus maze and light/dark box were employed to measure effect of forskolin on anxiety and the noted activity was compared with that of diazepam. cAMP levels were also measured in plasma of mice.Results: Forskolin produced a significant antianxiety- like activity in unstressed mice and stressed mice. Diazepam produced a significant antianxiety- like activity in unstressed mice but not in stressed mice. The noted antianxiety activity of forskolin was accompanied by a significant elevation of cAMP levels.Conclusions: The present findings contribute to suggest a non– receptor mediated anti-anxiety action of a forskolin, acting through cAMP elevation, thus avoiding receptor-mediated adverse effect profile of the conventional anxiolytics.Â

Farmacología de productos naturales: un enfoque reciente en Calotropis gigantea y Calotropis procera

The authors are thankful to the Dr. Ritu Gilhotra, Principal, School of Pharmacy, Suresh Gyanvihar University, Jaipur, Rajasthan, India. For valuable guidanceIntroduction: Since ancient times, people have used medicinal plants to treat varied diseases. Medicinal plants are the important source of drugs, and many of them that are currently available in the pharmaceutical market are obtained from plant sources. Calotropis gigantea and Calotropis procera are small shrub, which are used conventionally to treat many diseases such as cancer, diabetes and intestinal disease in African and Asian countries. There have been always an increased focus on primary health care: basic health care which is effective and affordable by developing countries. Objective: This paper aims to review the pharmacological and pharmacognostical features of Calotropis gigantea and Calotropis procera Method: Brief review on recent literature carried out using Scopus, Google scholar. Result and Discussion: Several studies provide evidence of their antioxidant, analgesic, anti-inflammatory, anti-diarrheal, anticonvulsant, anti-malarial, hepatoprotective, antitumor, antimicrobial and antinociceptive properties. Conclusion: Species of Calotropis not widely recognized showed different pharmacological actions, due to the presence of effective secondary metabolites.Introducción: Desde la antigüedad, las personas han utilizado plantas medicinales para tratar diversas enfermedades. Las plantas medicinales son la fuente importante de los fármacos, y muchas de ellas, que están actualmente disponibles en el mercado farmacéutico, se obtienen de fuentes vegetales. Calotropis gigantea y Calotropis procera son arbustos pequeños que se utilizan convencionalmente para tratar muchas enfermedades como el cáncer, la diabetes y las enfermedades intestinales en países africanos y asiáticos. Siempre se ha prestado una mayor atención a la Atención Primaria de salud: la atención básica de la salud es eficaz y asequible para los países en desarrollo. Objetivos: Este trabajo tiene como objetivo revisar las características farmacológicas y farmacognosóticas de Calotropis gigantea y Calotropis procera. Método: Breve revisión de la literatura reciente realizada utilizando Scopus, Google scholar. Resultado y discusión: Varios estudios proporcionan evidencia de sus propiedades antioxidantes, analgésicas, antiinflamatorias, antidiarreicas, anticonvulsivas, antipalúdicas, hepatoprotectoras, antitumorales, antimicrobianas y anti-nociceptivas. Conclusión: Especies de Calotropis no ampliamente reconocido mostraron diferentes acciones farmacológicas, debido a la presencia de metabolitos secundarios efectivos

Evaluation of Polyherbal Anticancer Tablets: A Review

Cancer is a malignant abnormal growth of cells, one of the most dreaded and complex diseases. It concerns with several tempo spatial changes in cell composition, which finally lead to neoplasia. Various types of cancers have been reported. Chemotherapy, radiation, and/or surgery may cure them. Herbal remedies are supposed to be harmless as they cause fewer complications and are less likely to habitual. Antioxidant compositions of therapeutic plants show the anticancer activity and therefore, use of different proportions of the active components to formulate various standardized preparation with single or multiple components for their synergistic effects play a crucial role in curing cancer. Evaluation parameters to assess the in vitro anticancer activity includes Caspase-3, Caspase-9, alamar blue, LDH assay, XTT assay, sulforhodamine-B assay, MTT assay, DNA fragmentation assay, neutral red uptake cytotoxic assay, tryphan blue assay. Evaluation of dried extract or granules includes bulk density, tapped density, Carr’s index, Hausner’s ratio, angle of repose while the tablets evaluated by drug-excipient compatibility study by FT-IR, stability studies, hardness, thickness, weight variation, friability, disintegration time and dissolution test

A RAPID, SENSITIVE AND VALIDATED ULTRA PERFORMANCE LIQUID CHROMATOGRAPHY AND TANDEM MASS SPECTROMETRY METHOD FOR DETERMINATION OF PAROMOMYCIN IN MICE PLASMA: APPLICATION TO PHARMACOKINETIC STUDY

Objective: To develop and validate simple, sensitive, accurate and selective UPLC-MS/MS method for quantification of paromomycin (PARO) in mice plasma.Methods: Precipitation method was used for the extraction of plasma samples, an aliquot of 25 µl plasma samples was extracted using 10% perchloric acid in water. Chromatographic separation was performed using waters acquity ultra-performance liquid chromatography (UPLC) columns, BEH HILIC (50 mm× 2.1 mm, 1.7 µm) by a gradient mixture of acetonitrile and water (both containing 0.005% v/v trifluro acetic acid) as a mobile phase at the flow rate of 0.2 ml/min. The analyte was protonated in the positive electrospray ionization (ESI) interface and detected in multiple reactions monitoring (MRM) modes using the transition m/z 308.60-455.30.Results: The method had a short chromatographic run time of 3 min. Calibration curves were linear over wide ranges of 50.51-5019.22 ng/ml. The between and within-batch precision and accuracy of the method was determined by using 4 quality control samples, the highest % CV observed was 11.06. The mean recovery values are 78.17, 101.17 and 92.58 at low, medium and high-quality control levels; respectively.Conclusion: It was concluded that the developed and validated UPLC-MS/MS method was rapid, sensitive, accurate, precise, linear, and specific. Therefore, this method can be used for quantification of PARO in mice plasma with various advantages over the reported methods