Ampelopsis grossedentata is a wildly used herb in South China as sleep aid beverage for many years. Yet the active ingredients and mechanisms of this herb were unknown. In the present study, extract from Ampelopsis grossedentata which we named ECBRC-AG, and one of its active ingredient myricetin were proved having significant hypnotic/sedative effects in multiple animal models. ECBRC-AG shortened sleep latency, increase NREM sleep and decrease locomotor activity when treated before the onset of light period in rats. ECBRC-AG could decrease active awake and increase REM sleep in the late part of light period. ECBRC-AG also decreased the caffeine induced hyperactivity in rats. Among the three suspected active ingredients from ECBRC-AG, myricetin showed similar active profile with ECBRC-AG. Myricetin increased NREM and REM sleep, decreased sleep latency, decreased locomotor activity and also active awake. All the above evidences have implicated that myricetin is the most important active ingredient of ECBRC-AG ECBRC-AG and myricetin did not show any obvious side effects on rats. / Based on these findings, we propose that myricetin facilitates GABA function on PVN neurons through a T-type calcium channel and CaM-KII mechanism. The hypnotic/sedative effects of ECBRC-AG and myricetin are mediated by PVN. ECBRC-AG treatment decreased corticosterone levels in rats, which also indicated that PVN/HPA axis was the target of these herbal derivates. PVN has broad interactions with GABAergic, hypocretinergic, cytokine and NPY system and all these systems are proved to be deeply involved in sleep regulation. / In conclusion, the present study has identified that myricetin is the most important active ingredient of the herbal extract ECBRC-AG. We confirmed the hypnotic/sedative effects of ECBRC-AG and myricetin on rats, and also revealed the different action profiles of these herbal derivates compared with zolpidem. T-type calcium channels and the HPA axis were shown to be involved in the mechanisms of ECBRC-AG and myricetin, indicating that they may be the new targets for insomnia treatment with these herbal derivates. / Insomnia is the most common sleep disorder and affects about one third of the general population. Insomnia is always combined with physical and mental illness, as either a consequence or a contributing factor. Insomnia produces sleepiness, impairment in psychomotor performance, absenteeism, frequent accidents, memory impairment and a high risk of depression. Pharmacologic therapies are the most important interventions for insomnia. However, the currently available hypnotics are associated with residual effects and risks of abuse and dependence. More efficient and safe hypnotics are needed. / The DNA array and RT-PCR studies revealed that GABA, hypocretin, cytokine and NPY systems were involved in the mechanisms of ECBRC-AG and myricetin. In calcium imaging study, we found that myricetin induced a transient Ca 2+ influx in the primary culture of rat hypothalamus neurons. This Ca2+ influx could be blocked by T-type channel blocker mibefradil. RT-PCR study also showed that ECBRC-AG and myricetin treatment changed the mRNA expression level of T-type calcium channel al G subunit in rat hypothalamus. The present results are consistent with our previous study showing that myricetin enhanced GABA function in the neurons of rat hypothalamic paraventricular nucleus (PVN), and that blocking CaM-KII pathway eliminated this effect. / Zhang, Xiaohu. / "March 2008." / Adviser: Chan Hsiao Chang. / Source: Dissertation Abstracts International, Volume: 70-03, Section: B, page: 1516. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2008. / Includes bibliographical references (p. 156-174). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.
| Identifer | oai:union.ndltd.org:cuhk.edu.hk/oai:cuhk-dr:cuhk_344201 |
| Date | January 2008 |
| Contributors | Zhang, Xiaohu, Chinese University of Hong Kong Graduate School. Division of Physiology. |
| Source Sets | The Chinese University of Hong Kong |
| Language | English, Chinese |
| Detected Language | English |
| Type | Text, theses |
| Format | electronic resource, microform, microfiche, 1 online resource (174 p. : ill.) |
| Rights | Use of this resource is governed by the terms and conditions of the Creative Commons “Attribution-NonCommercial-NoDerivatives 4.0 International” License (http://creativecommons.org/licenses/by-nc-nd/4.0/) |
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