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      Antianxiety-Like Effects of Chimpi (Dried Citrus Peels) in the Elevated Open-Platform Test

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          Abstract

          Dried citrus peels (Chimpi) is one of the most common natural medicines with qi (energy flow) rectifying and shi (dampness) drying actions, which originates from Citrus unshiu, and/or C. reticulata according to the definition of the pharmacopoeiae of Japan and China. In this study, the pharmacological effects of their extracts and major chemical constituents hesperidin and its aglycone hesperetin on anxiety were examined with an anxiety model of elevated open-platform test using ICR male mice (6-week-old) and total duration of freezing was decreased in fluoxetine-treated mice, which is a simple and highly sensitive to the effects of serotonergic anxiolytics. Moreover, yokukansankachimpihange (YKH), a combination of yokukansan with Chimpi and Hange (Pinellia) was also examined because Chimpi is considered to play a crucial part in this formula against anxious symptoms in dementia patients. The results showed that Chimpi and YKH possess a significant anxiolytic-like effect similar to that of fluoxetine, suggesting that they might be similar to fluoxetine in their pharmacological actions through the serotonergic neurotransmission pathway. Moreover, it also suggested that the major chemical constituent, hesperidin could be an active principle attributed to the antianxiety-like effects with a direct and indirect role via its aglycone hesperetin.

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          Neuroprotective effects of citrus flavonoids.

          Tsann-Long Hwang, Chin-En Yen, Shou-Ping Shih (2012)
          Recent attention has been given to the influence of dietary factors on health and mental well-being. Oxidative stress is associated with many diseases including neurodegenerative disorders. Dietary flavonoids exert cardioprotective, chemopreventive, and neuroprotective effects. The biological activities of flavonoids have been attributed to their antioxidant, anti-inflammatory, and signaling properties. A clear understanding of the mechanisms of action, as either antioxidants or signaling molecules, is crucial for the application of flavonoids as interventions in neurodegeneration and as brain foods. Citrus flavonoids exert little adverse effect and have low or no cytotoxicity to healthy, normal cells. The main citrus flavonoids can also traverse the blood-brain barrier; hence, they are promising candidates for intervention in neurodegeneration and as constituents in brain foods. In this review, we discuss the bioactivity, multiple neuroprotection mechanisms, and antioxidant and signaling properties of citrus flavonoids. Receptor-mediated neuroprotective actions and parallel signaling pathways are also explored. Finally, the induction of cellular defense proteins against oxidative stress and neurotoxicity by hesperetin, a main and widespread citrus flavonoid, are also discussed. It is suggested that citrus fruits, which are rich in abundant sources of hesperetin and other flavonoids, are promising for the development of general food-based neuroprotection and brain foods.
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            Yokukansan in the treatment of behavioral and psychological symptoms of dementia: a systematic review and meta-analysis of randomized controlled trials.

            Yuki Matsuda, Taro Kishi, Hiroto Shibayama … (2013)
            There is currently no meta-analysis of the efficacy and tolerability of Yokukansan in the treatment of behavioral and psychological symptoms of dementia. We used information obtained from the PubMed and Cochrane Library databases until October 2012. We conducted a systematic review and meta-analysis of individual patient data from randomized controlled trials comparing Yokukansan with usual care (UC, i.e., controls). Standardized mean difference and weighted mean difference were calculated. All studies used the Neuropsychiatric Inventory (NPI) for the evaluation of behavioral and psychological symptoms of dementia. Four relevant studies (total n = 236) were identified. Yokukansan was superior to UC in the reduction of total NPI scores (p = 0.0009, weighted mean difference = -7.20, I(2) = 0%). In addition, Yokukansan was more efficacious in reducing scores on the NPI subscale (delusions, hallucinations, and agitation/aggression) than UC (p < 0.00001-0.0009). Yokukansan treatment also improved activities of daily living scores compared with UC (p = 0.04, standardized mean difference = -0.32, I(2) = 0%). Mini-mental state examination scores did not differ between the Yokukansan and UC treatment groups. Yokukansan was not different from UC regarding discontinuation due to any cause. Our results suggest that Yokukansan has a beneficial effect on NPI and on ADL scores and that Yokukansan seems to be a well-tolerated treatment. Copyright © 2013 John Wiley & Sons, Ltd.
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              Rikkunshito and 5-HT2C receptor antagonist improve cisplatin-induced anorexia via hypothalamic ghrelin interaction.

              Koji Yakabi, Susumu Kurosawa, Mitsuo Tamai … (2010)
              Circulating ghrelin concentration regulates appetite behavior, but no study thus far has focused on the role of central ghrelin in anorexia after chemotherapy. To clarify the action mechanisms of rikkunshito (RKT), a traditional Japanese medicine, on cisplatin-induced anorexia, we attempted to elucidate its effect on hypothalamic ghrelin receptor expression in cisplatin-induced anorexia. We first examined the effects of an intracerebroventricular (ICV) injection of exogenous ghrelin on food intake with or without cisplatin treatment, and the effects of cisplatin or m-chlorophenylpiperazine (mCPP), a 5-HT2C receptor agonist, on hypothalamic growth hormone secretagogue receptor 1a (GHS-R1a) mRNA expression. To identify the mechanism of cisplatin-induced decrease in hypothalamic GHS-R1a mRNA expression, we evaluated the effects of SB242084HCl, a 5-HT2C receptor antagonist, and RKT on hypothalamic GHS-R1a gene expression, along with the effect of coadministration of a GHS-R1a antagonist on decreased food intake. Compared to vehicle controls, an ICV-injected rat ghrelin failed to inhibit the decrease in food intake in cisplatin-treated rats. Hypothalamic GHS-R1a gene expression was significantly reduced after cisplatin or mCPP treatment, and the induced decrease was reversed by SB242084HCl or RKT, but not granisetron or ondansetron, both of which are 5-HT3 receptor antagonists. Their suppressive effect on the decrease in food intake was abolished by coadministration of the GHS-R1a antagonist. Administration of RKT or SB242084HCl reversed the decrease in food intake induced by mCPP injection. The improvement by RKT on decreased food intake after cisplatin treatment was partly mediated by hesperidin and isoliquiritigenin, components of RKT. Cisplatin-induced anorexia may worsen because of decreased hypothalamic GHS-R1a gene expression. A 5-HT2C receptor antagonist and RKT suppressed cisplatin-induced anorexia by inhibiting reduction of GHS-R1a signal transduction in the hypothalamus. Copyright 2010 Elsevier B.V. All rights reserved.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Molecules
                Journal ID (iso-abbrev): Molecules
                Journal ID (publisher-id): molecules
                Title: Molecules
                Publisher: MDPI
                ISSN (Electronic): 1420-3049
                Publication date (Electronic): 20 August 2013
                Publication date Collection: August 2013
                Volume: 18
                Issue: 8
                Pages: 10014-10023
                Affiliations
                Kampo Research Laboratories, Kracie Pharma Ltd., Kanebo machi 3-1, Takaoka City, Toyama 933-0856, Japan; E-Mails: ito_aya@ 123456phm.kracie.co.jp (A.I.); shin_noriyuki@ 123456phm.kracie.co.jp (N.S.); tsuchida@ 123456phm.kracie.co.jp (T.T.); t_okubo@ 123456phm.kracie.co.jp (T.O.)
                Author notes
                [* ] Author to whom correspondence should be addressed; E-Mail: h_norimoto@ 123456phm.kracie.co.jp ; Tel.: +81-766-28-7953 (ext. 540); Fax: +81-766-28-7960.
                Article
                Publisher ID: molecules-18-10014
                DOI: 10.3390/molecules180810014
                PMC ID: 6270198
                PubMed ID: 23966085
                SO-VID: d27d5155-2561-4169-8a47-fee55b299f7f
                Copyright © © 2013 by the authors; licensee MDPI, Basel, Switzerland.
                License:

                This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/3.0/).

                History
                Date received : 16 July 2013
                Date revision received : 09 August 2013
                Date accepted : 16 August 2013
                Categories
                Subject: Article

                Keywords: dried citrus peels (chimpi),antianxiety-like effects,hesperidin,hesperetin,yokukansankachimpihange,elevated open-platform test
                Data availability:
                Keywords: dried citrus peels (chimpi), antianxiety-like effects, hesperidin, hesperetin, yokukansankachimpihange, elevated open-platform test

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