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      Soporific Effect of Modified Suanzaoren Decoction and Its Effects on the Expression of CCK-8 and Orexin-A

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          Abstract

          Suanzaoren decoction (SZRT), a classic Chinese herbal prescription, has been used as a treatment for insomnia for more than a thousand years. However, recent studies have found no significant effects of SZRT as a treatment for insomnia caused by gastric discomfort. Herein, we studied the effects of modified Suanzaoren decoction (MSZRD) on gastrointestinal disorder-related insomnia. The main constituents of MSZRD were spinosin (2.21 mg/g) and 6-feruloylspinosin (0.78 mg/g). A pentobarbital-induced animal model of insomnia showed that MSZRD shortened sleep latency and prolonged sleep time of the male Institute of Cancer Research (ICR) mice treated for 7 days with oral MSZRD. Sprague-Dawley male rats were treated daily with oral MSZRD or placebo for 11 days and then deprived of sleep for the last 4 days to establish a model of insomnia. Of note, MSZRD-treated animals had significantly improved body weight, organ index scores, and fecal moisture relative to placebo-treated animals, as well as reduced temperature. Sleep-deprived rats exhibited more exploratory behaviors in an open-field anxiety test; however, this effect was significantly reduced in MSZRD-treated animals. We found that MSZRD treatment decreased gastric acid pH, decreased the production of gastrin, pepsin, and Orexin-A, and increased the expression of MTL and CCK-8. Importantly, serum GABA concentration was increased by treatment with MSZRD, as reflected by a decreased Glu/GABA ratio. Treated animals had increased the expression of GAD1, GABARA1, and CCKBR but decreased the expression of Orexin R1. In summary, these results suggest that MSZRD has soporific and gastroprotective effects that may be mediated by differential expression of CCK-8 and Orexin-A.

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          Neural substrates of awakening probed with optogenetic control of hypocretin neurons.

          The neural underpinnings of sleep involve interactions between sleep-promoting areas such as the anterior hypothalamus, and arousal systems located in the posterior hypothalamus, the basal forebrain and the brainstem. Hypocretin (Hcrt, also known as orexin)-producing neurons in the lateral hypothalamus are important for arousal stability, and loss of Hcrt function has been linked to narcolepsy. However, it is unknown whether electrical activity arising from Hcrt neurons is sufficient to drive awakening from sleep states or is simply correlated with it. Here we directly probed the impact of Hcrt neuron activity on sleep state transitions with in vivo neural photostimulation, genetically targeting channelrhodopsin-2 to Hcrt cells and using an optical fibre to deliver light deep in the brain, directly into the lateral hypothalamus, of freely moving mice. We found that direct, selective, optogenetic photostimulation of Hcrt neurons increased the probability of transition to wakefulness from either slow wave sleep or rapid eye movement sleep. Notably, photostimulation using 5-30 Hz light pulse trains reduced latency to wakefulness, whereas 1 Hz trains did not. This study establishes a causal relationship between frequency-dependent activity of a genetically defined neural cell type and a specific mammalian behaviour central to clinical conditions and neurobehavioural physiology.
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            Prevalence of chronic insomnia in adult patients and its correlation with medical comorbidities

            Introduction: Insomnia is one of the common but neglected conditions seen in family practice with long term and serious effects on health of a patient. Family physicians have the responsibility of diagnosing and adequately treating this. This study was done to find the prevalence of chronic insomnia in adult patients visiting a family medicine outpatient department (OPD) in a hospital and to assess the risk factors and co morbidities associated with it. Materials and Methods: A cross-sectional study was done in the family medicine OPD at St. Philomena's Hospital, Bengaluru. All adult patients attending the OPD from September 1 to October 30, 2015 were enrolled in the study after obtaining written consent. Athens Insomnia Scale was used to diagnose insomnia and information regarding medical co morbidities was collected. Data was analyzed for the prevalence of insomnia and its association with co morbidities. Results: Chronic insomnia was seen in 33% of the adult population sampled. Increasing age and diabetes were significantly associated with insomnia, while other socioeconomic factors and co morbidities were not significantly associated. Twenty-seven percent of patients who had insomnia did not perceive the condition, which was statistically significant. Conclusion: Insomnia is a common sleep disorder which is many times missed by a primary care physician until/unless asked for. Since there is a higher incidence with increasing age and co morbidities such as diabetes, all patients, especially middle-aged and diabetics, should be screened for insomnia by the primary care physician with a self assessed questionnaire and counseled.
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              GABA mechanisms and sleep

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                Author and article information

                Contributors
                Journal
                Evid Based Complement Alternat Med
                Evid Based Complement Alternat Med
                ECAM
                Evidence-based Complementary and Alternative Medicine : eCAM
                Hindawi
                1741-427X
                1741-4288
                2020
                16 June 2020
                16 June 2020
                : 2020
                : 6984087
                Affiliations
                1Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, No. 18, Chaowang Road, Xiacheng District, Zhejiang University of Technology, Hangzhou, Zhejiang 310014, China
                2Zhejiang Senyu Co., Ltd., No. 8 Wanmao Road, Choujiang Street, Yiwu, Zhejiang 322099, China
                3College of Pharmaceutical Science, No. 548, Binwen Road, Binjiang District, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310014, China
                Author notes

                Academic Editor: Juntra Karbwang

                Author information
                https://orcid.org/0000-0002-1918-8854
                https://orcid.org/0000-0003-1875-6335
                https://orcid.org/0000-0003-2732-4905
                https://orcid.org/0000-0001-8807-5071
                Article
                10.1155/2020/6984087
                7315314
                765b9e5a-1990-41be-9690-5d7b4d8a8e95
                Copyright © 2020 Liang-Hui Zhan et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 31 January 2020
                : 2 May 2020
                : 15 May 2020
                Funding
                Funded by: National Key Research and Development Program
                Award ID: 2017YFC1702200
                Funded by: National Natural Science Foundation of China
                Award ID: 81673638
                Award ID: 81874352
                Funded by: Ten-Thousand Talents Program of Zhejiang Province
                Award ID: ZJWR0102035
                Categories
                Research Article

                Complementary & Alternative medicine
                Complementary & Alternative medicine

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