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      Identifying the active components of Baihe–Zhimu decoction that ameliorate depressive disease by an effective integrated strategy: a systemic pharmacokinetics study combined with classical depression model tests

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          Abstract

          Background

          Modern pharmacological studies have demonstrated that Baihe–Zhimu decoction (BZD) has antidepressant effects. However, the complex composition and lack of clear evaluation standards for BZD make it less likely to be understood and accepted than evidence-based active natural compounds.

          Methods

          In this study, an effective method for the identification of antidepressant components was demonstrated and applied to BZD. The first step was to evaluate the efficacy of BZD by the forced swimming test (FST) and the tail suspension test (TST), followed by successive quantitative analyses of the absorbed constituents at different stages, such as before hepatic disposition, liver distribution, after hepatic disposition and brain distribution after the oral administration of BZD. Finally, the compounds detected in the brain were confirmed by activity testing.

          Results

          Our investigation observed that timosaponin BII and timosaponin BIII were accurately determined in the brain after oral administration of BZD, and they were further confirmed to reduce the immobility time in the FST and TST. As described above, timosaponin BII and timosaponin BIII were used to scientifically and reasonably explain the effective chemical basis of the effect of BZD on depression.

          Conclusions

          This research affords an effective method to discover lead molecules for antidepressants from traditional Chinese medicine.

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          Most cited references28

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          Inflammation Effects on Motivation and Motor Activity: Role of Dopamine.

          Motivational and motor deficits are common in patients with depression and other psychiatric disorders, and are related to symptoms of anhedonia and motor retardation. These deficits in motivation and motor function are associated with alterations in corticostriatal neurocircuitry, which may reflect abnormalities in mesolimbic and mesostriatal dopamine (DA). One pathophysiologic pathway that may drive changes in DAergic corticostriatal circuitry is inflammation. Biomarkers of inflammation such as inflammatory cytokines and acute-phase proteins are reliably elevated in a significant proportion of psychiatric patients. A variety of inflammatory stimuli have been found to preferentially target basal ganglia function to lead to impaired motivation and motor activity. Findings have included inflammation-associated reductions in ventral striatal neural responses to reward anticipation, decreased DA and DA metabolites in cerebrospinal fluid, and decreased availability, and release of striatal DA, all of which correlated with symptoms of reduced motivation and/or motor retardation. Importantly, inflammation-associated symptoms are often difficult to treat, and evidence suggests that inflammation may decrease DA synthesis and availability, thus circumventing the efficacy of standard pharmacotherapies. This review will highlight the impact of administration of inflammatory stimuli on the brain in relation to motivation and motor function. Recent data demonstrating similar relationships between increased inflammation and altered DAergic corticostriatal circuitry and behavior in patients with major depressive disorder will also be presented. Finally, we will discuss the mechanisms by which inflammation affects DA neurotransmission and relevance to novel therapeutic strategies to treat reduced motivation and motor symptoms in patients with high inflammation.
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            A systematic review on the efficacy, safety and types of Chinese herbal medicine for depression.

            Chinese herbal medicine (CHM) is one of the commonly used complementary and alternative medicine therapies for major depressive disorder. The objective of this study was to review the efficacy, safety and types of CHM for depression. We systematically searched key databases (9 Chinese and 7 English) up until May 2013 for randomized controlled trials (RCTs) and examined 7 systematic reviews for additional articles. Methodological quality was assessed by modified Jadad scale and Cochrane's risk of bias assessment. Only studies with moderate methodological quality, defined as modified Jadad scale score ≥3, were included in meta-analysis for efficacy. Of the 296 RCTs that were assessed in details, 278 (93.9%) had modified Jadad scale score < 3, and only 21 scored ≥ 3. The frequently used formulas were Xiao Yao decoction, Chaihu Shugan decoction and Ganmai Dazao decoction; while Chaihu, Bai Shao and Fu Ling were the frequently used single herb. Meta-analyses showed that CHM monotherapy was better than placebo and as effective as antidepressants in reducing Hamilton Depression Rating Scale (HDRS) score (CHM vs. placebo: mean difference: -7.97, 95% CI: -10.25 to -5.70, P < 0.00001, 2 studies; CHM vs. antidepressants: mean difference: 0.01, 95% CI: -0.28 to 0.30, P = 0.95, 7 studies). CHM were associated with less adverse events than antidepressants, and adding CHM to antidepressants reduced adverse events. Despite the overall positive results, due to the small number of studies with sufficient methodological quality, it is premature to accurately conclude the benefits and risks of CHM for depression.
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              Depression: the best way forward.

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                Author and article information

                Contributors
                lf86614@126.com
                cghsimm@126.com
                Journal
                Chin Med
                Chin Med
                Chinese Medicine
                BioMed Central (London )
                1749-8546
                24 September 2019
                24 September 2019
                2019
                : 14
                : 37
                Affiliations
                [1 ]ISNI 0000 0004 1797 7280, GRID grid.449428.7, College of Pharmacy, , Jining Medical University, ; Rizhao, 276826 People’s Republic of China
                [2 ]ISNI 0000000119573309, GRID grid.9227.e, Shanghai Research Center for Modernization of Traditional Chinese Medicine, Shanghai Institute of Materia Medica, , Chinese Academy of Science, ; Shanghai, 201203 People’s Republic of China
                Author information
                http://orcid.org/0000-0001-9209-7484
                Article
                254
                10.1186/s13020-019-0254-9
                6757420
                31572489
                329f3319-2662-47d3-b642-5dcb43e963e7
                © The Author(s) 2019

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 5 June 2019
                : 4 September 2019
                Funding
                Funded by: The National Science and Technology Major Project of the Ministry of Science and Technology of China
                Award ID: 2018ZX09731016-003
                Award ID: 2018ZX09201001-001-008
                Award Recipient :
                Funded by: A grant from the Focus on research and development plan in Shandong Province, China
                Award ID: 2018GSF119006
                Award Recipient :
                Funded by: The National Natural Science Foundation of China for Young Scientists
                Award ID: 81803828
                Award Recipient :
                Funded by: The General Financial Grant from China Postdoctoral Science Foundation
                Award ID: 2018M642123
                Award Recipient :
                Funded by: Youth Innovation Promotion Association of Chinese Academy of Sciences
                Award ID: 2019280
                Award Recipient :
                Categories
                Research
                Custom metadata
                © The Author(s) 2019

                Complementary & Alternative medicine
                baihe–zhimu decoction,antidepressant,timosaponin bii,timosaponin biii,drug discovery

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