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      A traditional poly-herbal formulation improves cognitive function in C57BL/6 mice Translated title: Una formulación tradicional de poli-hierbas mejora la función cognitiva en ratones C57BL/6

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          Abstract

          Abstract Introduction: Khamira Gawzaban Ambari Jadwar Ood Saleeb Wala (KGAJOS) is a polyherbal compound Unani Pharmacopoeial formulation described in traditional Unani texts as Muqawwi-e-Aza-e-Raeesa (tonic for brain, heart, liver and stomach). KGAJOS is reported to possess anxiolytic and antidepressant activity in mice. Though it is used clinically for various neurological conditions, preclinical efficacy of this formulation in learning and memory enhancement / improvement is not established. Method: KGAJOS was evaluated for cognitive function improvement activity using Morris water maze test in C57BL/6 mice. Piracetam was used as positive control for comparison. Anymaze video tracking software was used for tracking the path of mice in pool as per standard protocol. Results: During probe trial in Morris water maze test, a significant increase in time spent in platform quadrant was observed at 1000 and 1500 mg/kg bw of KGAJOS (p<0.01 and 0.001, respectively) as well as in piracetam group (p<0.01) compared to vehicle control. Latency to reach the platform quadrant (escape latency) was significantly reduced (p<0.001) in piracetam and KGAJOS group at 1000 and 1500 mg/kg bw compared to vehicle control. No change in time spent in platform quadrant and escape latency was observed at 500 mg/kg bw of KGAJOS. Conclusions: Morris water maze experiment conducted in mice revealed improved learning and memory function of KGAJOS at the dose levels of 1000 and 1500 mg/kg bw whereas 500 mg/kg bw was not found to be effective. Observed efficacy of KGAJOS confirmed the traditional claims and usage of this formulation in conditions associated with cognition and memory.

          Translated abstract

          Resumen Introducción: Khamira Gawzaban Ambari Jadwar Ood Saleeb Wala (KGAJOS) es una formulación de Unani compuesto de poliherbal descrito como tónico para el cerebro, corazón, hígado y estómago. Este estudio se realizó para evaluar la eficacia preclínica de KGAJOS en el aprendizaje y la memoria. Método: Se evaluó la actividad de mejora de la función cognitiva de KGAJOS utilizando la prueba de laberinto de agua de Morris en ratones C57BL / 6. Se utilizó piracetam como control positivo. Se utilizó el software de seguimiento de video Anymaze para rastrear la ruta. Resultados: Durante la prueba de la sonda, se observó un aumento significativo en el tiempo empleado en el cuadrante de la plataforma a 1000 y 1500 mg / kg de peso corporal de KGAJOS (p <0,01 y 0,001, respectivamente) y en el grupo de piracetam (p <0,01) en comparación con el control. La latencia para alcanzar el cuadrante de la plataforma (latencia de escape) se redujo significativamente (p <0,001) en el grupo de piracetam y KGAJOS a 1000 y 1500 mg / kg de peso corporal en comparación con el control. Conclusiones: El experimento del laberinto de agua de Morris reveló una mejora en la función de aprendizaje y memoria con 1000 y 1500 mg / kg de peso corporal de KGAJOS, mientras que 500 mg / kg de peso corporal no fue efectivo. La eficacia observada de KGAJOS confirmó las afirmaciones tradicionales y el uso de esta formulación en condiciones asociadas con la cognición y la memoria.

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          Most cited references31

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          Dose translation from animal to human studies revisited.

          As new drugs are developed, it is essential to appropriately translate the drug dosage from one animal species to another. A misunderstanding appears to exist regarding the appropriate method for allometric dose translations, especially when starting new animal or clinical studies. The need for education regarding appropriate translation is evident from the media response regarding some recent studies where authors have shown that resveratrol, a compound found in grapes and red wine, improves the health and life span of mice. Immediately after the online publication of these papers, the scientific community and popular press voiced concerns regarding the relevance of the dose of resveratrol used by the authors. The animal dose should not be extrapolated to a human equivalent dose (HED) by a simple conversion based on body weight, as was reported. For the more appropriate conversion of drug doses from animal studies to human studies, we suggest using the body surface area (BSA) normalization method. BSA correlates well across several mammalian species with several parameters of biology, including oxygen utilization, caloric expenditure, basal metabolism, blood volume, circulating plasma proteins, and renal function. We advocate the use of BSA as a factor when converting a dose for translation from animals to humans, especially for phase I and phase II clinical trials.
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            Morris water maze: procedures for assessing spatial and related forms of learning and memory.

            The Morris water maze (MWM) is a test of spatial learning for rodents that relies on distal cues to navigate from start locations around the perimeter of an open swimming arena to locate a submerged escape platform. Spatial learning is assessed across repeated trials and reference memory is determined by preference for the platform area when the platform is absent. Reversal and shift trials enhance the detection of spatial impairments. Trial-dependent, latent and discrimination learning can be assessed using modifications of the basic protocol. Search-to-platform area determines the degree of reliance on spatial versus non-spatial strategies. Cued trials determine whether performance factors that are unrelated to place learning are present. Escape from water is relatively immune from activity or body mass differences, making it ideal for many experimental models. The MWM has proven to be a robust and reliable test that is strongly correlated with hippocampal synaptic plasticity and NMDA receptor function. We present protocols for performing variants of the MWM test, from which results can be obtained from individual animals in as few as 6 days.
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              The use of the Morris Water Maze in the study of memory and learning.

              Although the Morris Water Maze (MWM) was introduced only a few years ago, this technique has gained wide popularity, as the large number of publications in which it is employed, testifies. A review of the literature reveals that a wide variety of technical variables were used by the various research groups employing the MWM. This review describes the major changes in research variables, i.e., environmental variables, various manipulations, and the effects of diet or age on performance. The general principles of learning as demonstrated by the MWM are discussed.
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                Author and article information

                Journal
                ars
                Ars Pharmaceutica (Internet)
                Ars Pharm
                Universidad de Granada (Granada, Granada, Spain )
                2340-9894
                March 2021
                : 62
                : 1
                : 6-14
                Affiliations
                [1] Hyderabad orgnameNational Research Institute of Unani Medicine for Skin Disorders (under CCRUM) orgdiv1Pharmacology Research Laboratory India
                [2] New Delhi orgnameGovernment of India orgdiv1Under Ministry of AYUSH orgdiv2Central Council for Research in Unani Medicine India
                Article
                S2340-98942021000100006 S2340-9894(21)06200100006
                10.30827/ars.v62i1.15432
                3bdc3250-f517-4dd8-a9ed-04750364e2f0

                This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.

                History
                : 29 May 2020
                : 21 August 2020
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 31, Pages: 9
                Product

                SciELO Spain

                Categories
                Original Articles

                Memoria,Learning,Memory,Cognition,Polyherbal formulation,Morris water maze,Unani,Morris laberinto de agua,Formulación polivérica,Cognición,Aprendizaje

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