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      Terminalia arjuna bark extract attenuates picrotoxin-induced behavioral changes by activation of serotonergic, dopaminergic, GABAergic and antioxidant systems

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          Abstract

          Stress and emotion are associated with several illnesses from headaches to heart diseases and immune deficiencies to central nervous system. Terminalia arjuna has been referred as traditional Indian medicine for several ailments. The present study aimed to elucidate the effect of T. arjuna bark extract (TA) against picrotoxin-induced anxiety. Forty two male Balb/c mice were randomly divided into six experimental groups ( n = 7): control, diazepam (1.5 mg·kg −1), picrotoxin (1 mg·kg −1) and three TA treatemt groups (25, 50, and 100 mg/kg). Behavioral paradigms and PCR studies were performed to determine the effect of TA against picrotoxin-induced anxiety. The results showed that TA supplementation increased locomotion towards open arm (EPM) and illuminated area (light-dark box test), and increased rearing frequency (open field test) in a dose dependent manner, compared to picrotoxin ( P < 0.05). Furthermore, TA increased number of licks and shocks in Vogel’s conflict. PCR studies showed an up-regulation of several genes, such as BDNF, IP 3, D 2L, CREB, GABA A, SOD, GPx, and GR in TA administered groups. In conclusion, alcoholic extract of TA bark showed protective activity against picrotoxin in mice by modulation of genes related to synaptic plasticity, neurotransmitters, and antioxidant enzymes.

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          Most cited references 26

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          A neurotrophic model for stress-related mood disorders.

          There is a growing body of evidence demonstrating that stress decreases the expression of brain-derived neurotrophic factor (BDNF) in limbic structures that control mood and that antidepressant treatment reverses or blocks the effects of stress. Decreased levels of BDNF, as well as other neurotrophic factors, could contribute to the atrophy of certain limbic structures, including the hippocampus and prefrontal cortex that has been observed in depressed subjects. Conversely, the neurotrophic actions of antidepressants could reverse neuronal atrophy and cell loss and thereby contribute to the therapeutic actions of these treatments. This review provides a critical examination of the neurotrophic hypothesis of depression that has evolved from this work, including analysis of preclinical cellular (adult neurogenesis) and behavioral models of depression and antidepressant actions, as well as clinical neuroimaging and postmortem studies. Although there are some limitations, the results of these studies are consistent with the hypothesis that decreased expression of BDNF and possibly other growth factors contributes to depression and that upregulation of BDNF plays a role in the actions of antidepressant treatment.
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            Enhancing neuronal plasticity and cellular resilience to develop novel, improved therapeutics for difficult-to-treat depression.

            There is growing evidence from neuroimaging and ostmortem studies that severe mood disorders, which have traditionally been conceptualized as neurochemical disorders, are associated with impairments of structural plasticity and cellular resilience. It is thus noteworthy that recent preclinical studies have shown that critical molecules in neurotrophic signaling cascades (most notably cyclic adenosine monophosphate [cAMP] response element binding protein, brain-derived neurotrophic factor, bcl-2, and mitogen activated protein [MAP] kinases) are long-term targets for antidepressant agents and antidepressant potentiating modalities. This suggests that effective treatments provide both trophic and neurochemical support, which serves to enhance and maintainnormal synaptic connectivity, thereby allowing the chemical signal to reinstate the optimal functioning of critical circuits necessary for normal affective functioning. For many refractory patients, drugs mimicking "traditional" strategies, which directly or indirectly alter monoaminergic levels, may be of limited benefit. Newer "plasticity enhancing" strategies that may have utility in the treatment of refractory depression include N-methyl-D-aspartate antagonists, alpha-amino-3-hydroxy-5-methylisoxazole propionate (AMPA) potentiators, cAMP phosphodiesterase inhibitors, and glucocorticoid receptor antagonists. Small-molecule agents that regulate the activity f growth factors, MAP kinases cascades, and the bcl-2 family of proteins are also promising future avenues. The development of novel, nonaminergic-based therapeutics holds much promise for improved treatment of severe, refractory mood disorders. Copyright 2003 Society of Biological Psychiatry
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              Use of complementary and alternative medicine among patients with chronic diseases at outpatient clinics.

              The primary objective of this study was to evaluate the use of complementary and alternative medicine among patients with chronic diseases at outpatient clinics. Another aim was to identify demographic and socio-economic factors that are associated with CAM use. Face-to-face interviews of conveniently selected patients with chronic diseases were conducted in outpatient clinics of a general hospital. A validated data collection form was used to gather the information regarding pattern, perception, reasons, and perceived effect of CAM on the disease state. The other relevant information including demographics, diagnosis, indication, and treatment were collected from the patients' medical records. Out of 321 patients interviewed in this study, 205 patients were using some form of CAM, and thus the utilisation rate was 63.9%. A significant number of patients (35.5%) were using CAM for diabetes mellitus. Thirteen types of CAM were identified in the study with the most common being vitamins supplements (48.2%), herbal medicines (26.4%), ginseng (4.7%) and traditional Chinese medicine (4.0%). The patients with higher education level, higher income, and aged more than 50 years were independently associated with CAM use. Majority of the patients (77.6%) reported that their condition had improved by using CAM. The present study confirms the high frequency of CAM use among patients with chronic diseases in a Malaysian public hospital. The popularity of CAM indicated the patients' preference towards holistic approach to health care.
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                Author and article information

                Journal
                CJNM
                Chinese Journal of Natural Medicines
                Elsevier
                1875-5364
                20 August 2017
                : 15
                : 8
                : 584-596
                Affiliations
                1Applied Nutrition Division, Defence Food Research Laboratory, DRDO, Mysore-570011, Karnataka, India
                Author notes
                *Corresponding author: G Phani Kumar, Tel: 0821-2579485, E-mail: phani_dfrl@ 123456rediffmail.com

                These authors have no conflict of interest to declare.

                Article
                S1875-5364(17)30086-9
                10.1016/S1875-5364(17)30086-9
                Copyright © 2017 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

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